巨噬细胞移动抑制因子（MIF）调节细胞凋亡、细胞生长及周期的分子机制研究
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摘要
本论文研究通过酵母双杂交技术首次发现MIF与Bim相互结合,并通过invitro和in vivo蛋白结合技术证实了MIF和Bim的相互作用,并通过不同分子生物学技术证实了MIF参与反向调控Bim介导的线粒体凋亡途径,为内源性MIF提高细胞抗凋亡的能力提供了新的分子依据,并为研究线粒体凋亡途径中Bim的调节机制提供了新的思路。在研究MIF调节Bim介导的细胞凋亡的过程中,发现在HEK293细胞内抑制MIF表达后,细胞增殖活力降低,通过流式细胞仪细胞周期检测证实,MIF knockdown可阻碍细胞周期进程,导致细胞停滞于G0/G1期:为了阐明MIF调控细胞周期潜在的分子机制,我们应用microarray技术分析了MIF(+)和MIF(-)细胞的全基因组的mRNA表达谱差异,并通过细胞内信号通路分析方法结合MIF相关的基因差异性表达谱的数据,首次建立在细胞周期G1/S期进程中,以MIF knockdown为原点的信号通路调控网络,生动再现了在细胞内MIF影响细胞生长和细胞周期进程的动态的信号转导通路,这为揭示MIF在细胞内的分子生物学功能提供了有力的线索。
In the first section of the dissertation,we have employed a yeast two-hybrid system to isolate a novel Bim-interacting protein,macrophage migration inhibitory factor(MIF).The interaction between MIF and Bim was confirmed by both in vitro and in vivo protein interaction assays.Moreover,MIF may regulate pro-apoptotic activity of Bim and inhibit the release of cytochrome c from mitochondria to the cytosol during apoptosis.This study provides the novel insights into the MIF's anti-apopotic activity and Bim-mediated mitochondria-dependent apoptosis.
In the second section of the dissertation,we demonstrate siRNA-mediated knockdown of MIF results in inhibition of cell proliferation and G0/G1 cell cycle arrest in HEK293 cells.To elucidate the molecular mechanism of cell cycle perturbation following MIF knockdown, we employed microarray to investigate the genome-wide expression profile in MIF-deficient cells and normal cells.The dynamic model of MIF-dependent signaling pathways linked to cell cycle machinery were constructed through analyzing gene expression data in the context of the gene ontology and the known biological pathways. We have established an integrate and dynamic signaling network in the MIF knockdown cell.This study provides novel insights into the pleiotropic activities of endogenous MIF, especially its essential and crucial role in cell proliferation and the cell cycle.
In the first section of the dissertation,we have employed a yeast two-hybrid system to isolate a novel Bim-interacting protein,macrophage migration inhibitory factor(MIF).The interaction between MIF and Bim was confirmed by both in vitro and in vivo protein interaction assays.Moreover,MIF may regulate pro-apoptotic activity of Bim and inhibit the release of cytochrome c from mitochondria to the cytosol during apoptosis.This study provides the novel insights into the MIF's anti-apopotic activity and Bim-mediated mitochondria-dependent apoptosis.
In the second section of the dissertation,we demonstrate siRNA-mediated knockdown of MIF results in inhibition of cell proliferation and G0/G1 cell cycle arrest in HEK293 cells.To elucidate the molecular mechanism of cell cycle perturbation following MIF knockdown, we employed microarray to investigate the genome-wide expression profile in MIF-deficient cells and normal cells.The dynamic model of MIF-dependent signaling pathways linked to cell cycle machinery were constructed through analyzing gene expression data in the context of the gene ontology and the known biological pathways. We have established an integrate and dynamic signaling network in the MIF knockdown cell.This study provides novel insights into the pleiotropic activities of endogenous MIF, especially its essential and crucial role in cell proliferation and the cell cycle.
引文
[1]Allerson,C.R.,Sioufi,N.,Jarres,R.,Prakash,T.P.,Naik,N.,Berdeja,A.,Wanders,L.,Griffey,R.H.,Swayze,E.E.,and Bhat,B.2005.Fully 2'-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA.J.Med.Chem.48:901-904.
[2]Abe Y,Matsumoto S,Wei S,Nezu K,Miyoshi A,Kito K,Ueda N,Shigemoto K,Hitsumoto Y,Nikawa J,Enomoto Y.Cloning and characterization of a p53-related protein Idnase expressed in intedeukin-2-activated cytotoxic T-cells,epithelial tumor cell lines,and the testes.J Biol Chem 2001;276:44003-11.
[3]Adachi,M.,Zhao,X.,Imai,K.(2005) Nomenclature of dynein light chain-linked BH3-only protein Bim isoforms.Cell Death Differ.12,192-193
[4]Adams,J.M.,& Cory,S.(1998) The Bcl-2 protein family:Arbiters of cell survival.Science.281,1322-1326
[5]Allan G J,Tonner E,Szymanowska M,Shand JH,Kelly SM,Phillips K,Clegg RA,Gow IF,Beattie J,Flint DJ.Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor(IGF)-binding protein-5 results in progressive loss of both IGF-Ⅰ binding and inhibition of IGF-Ⅰ biological action.Endocrinology 2006;147:338-49.
[6]Amarasinghe AK,Calin-Jageman I.,Harmouch,A.,Sun,W.,and Nicholson,A.W.2001.Escherichia coli ribonuclease Ⅲ:Affinity purification of hexahistidine-tagged enzyme and assays for substrate binding and cleavage.Methods Enzymol.342:143-158.
[7]Amarzguioui M,Holen T,Babaie E,and Prydz H.2003.Tolerance for mutations and chemical modifications in a siRNA.Nucleic Acids Res.31:589-595.
[8]Amarzguioui M,Rossi J J,and Kim D.2005.Approaches for chemically synthesized siRNA and vector-mediated RNAi.FEBS Lett.579:5974-5981.
[9]Amati B.Integrating Myc and TGF-beta signalling in cell-cycle control.Nat Cell Biol.2001;3:E112-3.
[10]Arai K,Maruyama Y,Nishida M,Tanabe S,Takagahara S,Kozasa T,Mori Y,Nagao T,Kurose H.Differential requirement of G alpha12,G alpha13,G alphaq,and G beta gamma for endothelinol-induced c-Jun NH2-terminal kinase and extracellular signal-regulated kinase activation.Mol Pharmacol 2003;63:478-88.
[11]Attwooll C,Lazzerini Denchi E,Helin K.The E2F family:specific functions and overlapping interests.EMBO J 2004;23:4709-16.
[12]Ayroldi E,Migliorati G,Bruscoli S,Marchetti C,Zollo O,Cannarile L,D'Adamio F,Riccardi C.Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB.Blood 2001;98:743-53.
[13]Ayroldi E,Zollo O,Macchiarulo A,Di Marco B,Marchetti C,Riccardi C.Glucocorticoid-induced leucine zipper inhibits the Raf-extracellular signal-regulated kinase pathway by binding to Raf-1.Mol Cell Biol 2002;22:7929-41.
[14]Bacher M,Metz CN,Calandra T,Mayer K,Chesney J,Lohoff M,Gemsa D,Donnelly T,Bucala R.An essential regulatory role for macrophage migration inhibitory factor in T-cell activation.Proc Natl Acad Sci U S A.1996 Jul 23;93(15):7849-54.
[15]Baeuerle PA,Baltimore D.I kappa B:a specific inhibitor of the NF-kappa B transcription factor.Science 1988;242:540-6.
[16]Baldwin AS Jr,Azizkhan JC,Jensen DE,Beg AA,Coodly LR.Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts. Mol Cell Biol 1991; 11:4943-51.
[17]Bartel DP. 2004. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116:281-297.
[18]Baumann B, Weber CK, Troppmair J, Whiteside S, Israel A, Rapp UR, Wirth T. Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation. Proc Natl Acad Sci U S A 2000; 97:4615-20.
[19]Baumann R, Casaulta C, Simon D, Conus S, Yousefi S, Simon HU. (2003) Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway. FASEB J. 17(15), 2221-2230.
[20]Beattie J, Allan GJ, Lochrie JD, Flint DJ. Insulin-like growth factor-binding protein-5 (IGFBP-5): a critical member of the IGF axis. Biochem J 2006; 395:1-19.
[21]Beishuizen A, Thijs LG, Haanen C, Vermes I.Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness.J Clin Endocrinol Metab. 2001 Jun;86(6):2811-6.
[22]Bernhagen J, Bacher M, Calandra T, Metz CN, Doty SB, Donnelly T, Bucala R.An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.J Exp Med. 1996 Jan 1;183(1):277-82.
[23]Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, Manogue KR, Cerami A, Bucala R. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature. 1993;365(6448):756-9.
[24]Bernhagen J, Krohn R, Lue H, Gregory JL, Zemecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerie-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C. (2007) MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment, Nat Med. 13:587-596.
[25]Bemhagen J, Krohn R, Lue H, Gregory JL, Zemecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerie-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 2007;13:587-96.
[26]Bemhagen J, Mitchell RA, Calandra T, Voelter W, Cerami A, Bucala R. Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF).Biochemistry. 1994 Nov 29;33(47):14144-55.
[27]Bernstein E, Caudy AA, Hammond SM, and Hannon GJ. 2001. Role for a bidentate ribonuclease in theinitiation step of RNA interference. Nature 409:363-366.
[28]Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, and Malvy C. 2002. Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo. Biochem. Biophys. Res. Commun. 296:1000-1004.
[29]Beswick EJ, Suarez G, Pinchuk IV, Sierra JC, Reyes VE. (2006) Macrophage Migration Inhibitory Factor Binds to CD74 on Gastric Epithelial Cells and Induces Pro-carcinogenic Events during Helicobacter pyloriInfection. Proc Amer Assoc Cancer Res .47, 395-395.
[30]Birmingham A, Anderson EM, Reynolds A, Ilsley-Tyree D, Leake D, Fedorov Y, Baskerville S, Maksimova E., Robinson K, Karpilow J et al. 2006. 3' UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3:199-204.
[31]Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science 1966; 153:80-2.
[32]Bondensgaard K, Petersen M, Singh SK, Rajwanshi VK, Kumar R, Wengel J, and Jacobsen JP. 2000. Structural studies of LNA:RNA duplexes by NMR: Conformations and implications for RNase H activity. Chemistry (Easton) 6: 2687-2695.
[33]Bozza M. et al. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J. Exp. Med. 189, 341-346(1999).
[34]Braasch DA. and Corey DR. 2001. Locked nucleic acid (LNA): Fine-tuning the recognition of DNA and RNA. Chem. Biol. 8:1-7
[35]Braasch DA., Jensen S, Liu Y, Kaur K, Arar K, White MA, and Corey DR. 2003. RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42: 7967-7975.
[36]Breaker RR. and Joyce GF. 1994. A DNA enzyme that cleaves RNA. Chem. Biol. 1:223-229.
[37]Bridge AJ, Pebemard S, Ducraux A, Nicoulaz AL, and Iggo R. 2003. Induction of an interferon response by RNAi vectors in mammalian cells. Nat. Genet. 34:263-264.
[38]Brown FG, Nikolic-Paterson DJ, Chadban SJ, Dowling J, Jose M, Metz CN, Bucala R, Atkins RC. Urine macrophage migration inhibitory factor concentrations as a diagnostic tool in human renal allograft rejection. Transplantation. 2001 Jun 27;71(12):1777-83
[39]Brown FG, Nikolic-Paterson DJ, Hill PA, Isbel NM, Dowling J, Metz CM et al. Urine macrophage migration inhibitory factor reflects the severity of renal injury in human glomerulonephritis. J Am Soc Nephrol 2002; 13 (Suppl 1):S7-13.
[40]Brummelkamp, T.R., Bernards, R., and Agami, R. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550-553.
[41]Bucala R, Donnelly SC. Macrophage migration inhibitory factor a probable link between inflammation and cancer. Immunity 2007;26:281-5.
[42]Bucala R. (1996) MIF re-discovered: pituitary hormone and glucocorticoid-induced regulator of cytokine production. FASEB J. 7,19-24.
[43]Burger-Kentischer A, Goebel H, Seiler R, Fraedrich G, Schaefer HE, Dimmeler S et al. Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis. Circulation 2002; 105: 1561-6.
[44]Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995; 377:68-71.
[45]Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R.MIF as a glucocorticoid-induced modulator of cytokine production.Nature. 1995 Sep 7;377(6544):68-71.
[46]Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R.MIF as a glucocorticoid-induced modulator of cytokine production.Nature. 1995 Sep 7;377(6544):68-71.
[47]Calandra T, Bemhagen J, Mitchell RA, Bucala R.The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.J Exp Med. 1994 Jun 1;179(6):1895-902.
[48]Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hultner L, Heumann D, Mannel D, Bucala R, Glauser MP.Protection from septic shock by neutralization of macrophage migration inhibitory factor.Nat Med. 2000 Feb;6(2):164-70.
[49]Calandra T, Roger T, Macrophage migration inhibitory factor a regulator of innate immunity. Nat Rev Immunol. 3 (2003) 791-800.
[50]Calandra T, Roger T.Macrophage migration inhibitory factor a regulator of innate immunity. Nat Rev Immunol 2003; 3:791-800.
[51]Calandra T, Bernhagen J, Metz CN. (1995) MIF as a glucocorticoid-induced modulator of cytokine production. Nature.. 377, 68 - 71
[52]Castanotto D, Li H, and Rossi JJ. 2002. Functional siRNA expression from transfected PCR products. RNA 8:1454-1460
[53]Chang F, Steelman LS, Shelton JG, Lee JT, Navolanic PM, Blalock WL, Franklin R, McCubrey JA. Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway. Int J Oncol 2003; 22:469-80.
[54]Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410:37-40.
[55]Chang, J.T. 2004. An economic and efficient method of RNAi vector constructions. Anal. Biochem. 334: 199-200.
[56]Chen JZ, Ji CN, Gu SH, Li JX, Zhao EP, Huang Y, Huang L, Ying K, Xie Y, Mao YM.Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis. Int J Biochem Cell Biol. 2004 Aug;36(8):1554-61 Manning, F.C., & Patiemo, S.R. (1996) Apoptosis: inhibitor or instigator of carcinogenesis. Cancer Invest. 14,455-465
[57]Chen Z, Sakuma M, Zago AC, Zhang X, Shi C, Leng L, Mizue Y, Bucala R, Simon D. Evidence for a role of macrophage migration inhibitory factor in vascular disease.Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):709-14.
[58]Chen, L., Willis, S.N., Wei, A., Smith, B.J., Fletcher, J.I., Hinds, M.G., Colman, P.M., Day, C.L., Adams, J.M., Huang, D.C. (2005) Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell .17,393-403
[59]Chesney J, Metz C, Bacher M, Peng T, Meinhardt A, Bucala R. An essential role for macrophage migration inhibitory factor (MIF) in angiogenesis and the growth of a murine lymphoma. Mol Med. 1999 Mar;5(3):181-191
[60]Chi H, Lu B, Takekawa M, Davis RJ, Flavell RA. GADD45beta/GADD45gamma and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNgamma production in T cells. EMBO J 2004; 23:1576-86.
[61]Choi YS, Thomas T, Kotlyar A, Islam MT, and Baker Jr JR. 2005. Synthesis and functional evalution of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting. Chem. Biol. 12: 35-43.
[62]Claassen GF, Hann SR. A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta -induced cell-cycle arrest. Proc Natl Acad Sci U S A 2000; 97:9498-503.
[63]Cory S, Adams JM, (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer. 2: 647-656.
[64]Cunha FQ, Weiser WY, David JR, Moss DW, Moncada S, Liew FY.Recombinant migration inhibitory factorinduces nitric oxide synthase in murine macrophages.J Immunol. 1993 Mar 1;150(5):1908-12.
[65]Czaudema F, Fechtner M, Dames S, Aygun H, Klippel A, Pronk GJ, Giese K, and Kaufmann J. 2003a. Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res. 31: 2705-2716
[66]Czauderna F, Santel A, Hinz M, Fechtner M, Durieux B, Fisch G, Leenders F, Arnold W, Giese K, Klippel A, et al. 2003b. Inducible shRNA expression for application in a prostate cancer mouse model. Nucleic Acids Res. 31:e127
[67]Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y, Wang XF. Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc Natl Acad Sci U S A 1995; 92:5545-9.
[68]David, J.R. (1966) Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoidcell-antigen interaction. Proc Natl Acad Sci USA. 56, 72-77.
[69]de Jong YP, Abadia-Molina AC, Satoskar AR, Clarke K, Rietdijk ST, Faubion WA et al. Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol 2001; 2:1061- 6.
[70]De Smaele E, Zazzeroni F, Papa S, Nguyen DU, Jin R, Jones J, Cong R, Franzoso G. Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling. Nature 2001; 414:308-13.
[71]Del Sal G, Collavin L, Ruaro ME, Edomi P, Saccone S, Valle GD, Schneider C. Structure, function, and chromosome mapping of the growth-suppressing human homologue of the murine gas1 gene. Proc Natl Acad Sci U S A 1994;91:1848-52.
[72]Denkinger CM, Denkinger M, Kort JJ, Metz C, Forsthuber TG . In vivo blockade of macrophage migration inhibitory factor ameliorates acute experimental autoimmune encephalomyelitis by impairing the homing of encephalitogenic T cells to the central nervous system. J Immunol 2003; 170:1274- 82.
[73]Donnelly SC, Haslett C, Reid PT, Grant IS, Wallace WA, Metz CN, Bruce LJ, Bucala R.Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.Nat Med. 1997 Mar;3(3):320-3.
[74]Fingerle-Rowson G, Petrenko O, Metz CN, Forsthuber TG, Mitchell R, Huss R, Moll U, Muller W, Bucala R.The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting.Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9354-9.
[75]Donze O and Picard D. 2002. RNA interference in mammalian cells using siRNAs synthesized with T7 RNA polymerase. Nucleic Acids Res. 30: e46.
[76]Dykxhoorn DM. and Lieberman J. 2006. RUNNING INTERFERENCE: Prospects and obstacles to using small interfering RNAs as small molecule drugs. Annu. Rev. Biomed. Eng. 8:377-402.
[77]Dykxhoorn DM, Novina CD, and Sharp PA. 2003. Killing the messenger: Short RNAs that silence gene expression. Nat. Rev. Mol. Cell Biol. 4: 457-467.
[78]Eisenman RN. Deconstructing myc. Genes Dev 2001; 15(16):2023-30.
[79]Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, and Tuschl T. 2001a. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494-498.
[80]Elbashir SM, Harborth J, Weber K, and Tuschl T. 2002. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26:199-213.
[81]Elbashir, S.M., Lendeckel, W., and Tuschl, T. 2001b. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Dev. 15:188-200.
[82]Elbashir SM., Martinez J, Patkaniowska A, Lendeckel W, and Tuschl T. 2001c. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. 20: 6877-6888.
[83]Elmen J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y, Wahren B, Liang Z, Orum H, Koch T,et al. 2005. Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res. 33:439-447
[84]Evdokiou A, Cowled PA.Tumor-suppressive activity of the growth arrest-specific gene GAS1 in human tumor cell lines. Int J Cancer 1998; 75:568-77.
[85]Farokhzad OC, Jon S, Khademhosseini A, Tran TN, Lavan DA., and Langer R. 2004. Nanoparticle-aptamer bioconjugates: A new approach for targeting prostate cancer cells. Cancer Res. 64:7668-7672.
[86]Feldman AR. and Sen D. 2001. A new and efficient DNA enzyme for the sequence-specific cleavage of RNA. J.Mol.Biol. 313:283-294.
[87]Fingerie-Rowson G, Petrenko O, Metz CN, Forsthuber TG, Mitchell R, Huss R, Moll U, Muller W, Bucala R.2003; The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting. Proc Natl Acad Sci U S A 100:9354-9.
[88]Fire A, Xu S, Montgomery MK., Kostas SA, Driver SE, and Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-811.
[89]Foote A, Briganti EM, Kipen Y, Santos L, Leech M, Morand EF . Macrophage migration inhibitory factor in systemic lupus erythematosus. J Rheumatol 2004; 31:268- 73.
[90]Frigo DE, Tang Y, Beckman BS, Scandurro AB, Alam J, Burow ME, McLachlan JA. Mechanism of AP-1 -mediated gene expression by select organochlorines through the p38 MAPK pathway. Carcinogenesis 2004; 25:249-61.
[91]Froidevaux C, Roger T, Martin C, Glauser MP, Calandra T. Macrophage migration inhibitory factor and innate immune responses to bacterial infections. Crit Care Med. 2001 Jul;29(7 Suppl):S13-5.
[92]Galaktionov K, Chen X, Beach D. Cdc25 cell-cycle phosphatase as a target of c-myc. Nature 1996;382:511-7.
[93]Gando, S. et al. Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome. Intensive Care Med. 27,1187-1193 (2001).
[94]Gilley J, Coffer PJ, Ham J. (2003) FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons, J Cell Biol. 162:613-622.
[95]Girgenrath M, Weng S, Kostek CA, Browning B, Wang M, Brown SA, Winkles JA, Michaelson JS, Allaire N,
[96]Schneider P, Scott ML, Hsu YM, Yagita H, Flavell RA, Miller JB, Burkly LC, Zheng TS. TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration. EMBO J 2006; 25:5826-39.
[97]Grafia X, Reddy EP. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs),growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995; 11:211-9.
[98]Grimm, D. and Kay, M.A. 2006. Therapeutic short hairpin RNA expression in the liver: Viral targets and vectors. Gene Ther. 13: 563-575
[99]Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, and Kay MA. 2006.
[100]Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441: 537-541.
[101]Gross A, McDonnell JM, & Korsmeyer SJ. (1999) BCL-2 family members and the mitochondria in apoptosis. Gene Dev. 13,1899-1911
[102]Gupta S, Davis RJ. MAP kinase binds to the NH2-terminal activation domain of c-Myc. FEBS Lett 1994; 353:281-5.
[103]Gupta S, Schoer RA, Egan JE, Hannon GJ, and Mittal V. 2004. Inducible, reversible, and stable RNA interference in mammalian cells. Proc. Natl. Acad. Sci. 101:1927-1932.
[104]Hagemann T, Robinson SC, Thompson RG, Charles K, Kulbe H, Balkwill FR.Ovarian cancer cell-derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis.Mol Cancer Ther. 2007 Jul;6(7):1993-2002.
[105]Hall AH, Wan J, Shaughnessy EE, Ramsay Shaw B, and Alexander KA. 2004. RNA interference using boranophosphate siRNAs: Structure-activity relationships. Nucleic Acids Res. 32:5991-6000.
[106]Hallbrink M, Floren A, Elmquist A, Pooga M, Bartfai T, and Langel U. 2001. Cargo delivery kinetics of cell-penetrating peptides. Biochim. Biophys. Acta 1515:101-109.
[107]Han S, Mahato RI, Sung YK, and Kim SW. 2000. Development of biomaterials for gene therapy. Mol. Ther. 2:302-317.
[108]Hannon GJ. 2002. RNA interference. Nature 418: 244-251
[109]Harada N, Nakayama M, Nakano H, Fukuchi Y, Yagita H, Okumura K. Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells. Biochem Biophys Res Commun 2002; 299:488-93.
[110]Harada H, Quearry B, Ruiz-Vela A, & Korsmeyer SJ. (2004) Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity. Proc. Natl. Acad. Sci. USA. 101,15313-15317.
[111]Harbour JW, Dean DC. Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2000; 2:E65-7.
[112]Heath-Engel HM, & Shore GC, (2006) Mitochondrial membrane dynamics, cristae remodeling and apoptosis. Biochim Biophys Acta. 1763, 549-560.
[113]Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, and Bauer S. 2004. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303: 1526-1529
[114]Hilfiker-Kleiner D, Hilfiker A, Castellazzi M, Wollert KC, Trautwein C, Schunkert H, Drexler H. JunD attenuates phenylephrine-mediated cardiomyocyte hypertrophy by negatively regulating AP-1 transcriptional activity. Cardiovasc Res 2006; 71:108-17.
[115]Holen, T, Amarzguioui, M., Wiiger, M.T., Babaie, E., and Prydz, H. 2002. Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor. Nucleic Acids Res. 30:1757-1766.
[116]Hollins AJ, Benboubetra M, Omidi Y, Zinselmeyer BH, Schatzlein AG, Uchegbu IF, and Akhtar S. 2004. Evaluation of generation 2 and 3 poly(propylenimine) dendrimers for the potential cellular delivery of antisense oligonucleotides targeting the epidermal growth factor receptor. Phanm Res. 21:458-466.
[117]Homung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A., et al. 2005. Sequence-specific potent induction of IFN- by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11: 263-270.
[118]Huang B. and Kochanek S. 2005. Adenovirus-mediated silencing of huntingtin expression by shRNA. Hum. Gene Ther. 16: 618-626.
[119]Huang DC. and Strasser A. 2000. BH3-only proteins — essential initiators of apoptotic cell death. Cell 103,839-842.
[120]Hudson JD, Shoaibi MA, Maestro R, Camero A, Hannon GJ, Beach DH. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med. 1999 Nov 15; 190(10): 1375-82
[121]Hughes JA. and Rao GA. 2005. Targeted polymers for gene delivery. Expert Opin. Drug Deliv. 2:145-157. Hurlin PJ, Queva C, Koskinen PJ, Steingrimsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN. Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J 1995; 14:5646-59.
[121]lavarone A, Massague J. Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-beta in cells lacking the CDK inhibitor p15. Nature 1997; 387:417-22.
[122]lnoue H, Hayase Y, Imura A, Iwai S, Miura K, and Ohtsuka E. 1987. Synthesis and hybridization studies on two complementary nona(2'-O-methyl)ribonucleotides. Nucleic Acids Res. 15: 6131-6148.
[123]lshizaka K, Ishii Y, Nakano T. Sugie K. Biochemical basis of antigen-specific suppressor T cell factors: controversies and possible answers. Adv. Immunol. 74,1-60 (2000).
[124]lwabuchi K, Li B, Massa HF, Trask BJ, Date T, Fields S. Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2. J Biol Chem 1998; 273:26061-8.
[125]Jackson, A.L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., Johnson, J.M., Lim, L., Karpilow, J., Nichols, K., et al. 2006. Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12:1197-1205.
[126]Jaworski DC, Jasinskas A, Metz CN, Bucala R, Barbour AG.Identification and characterization of a homologue of the pro-inflammatory cytokine Macrophage Migration Inhibitory Factor in the tick, Amblyomma americanum.Insect Mol Biol. 2001 Aug;10(4):323-31.
[127]Ji, J., Wernli, M., Klimkait, T., and Erb, P. 2003. Enhanced gene silencing by the application of multiple specific small interfering RNAs. FEBS Lett. 552: 247-252.
[128]Jin R, De Smaele E, Zazzeroni F, Nguyen DU, Papa S, Jones J, Cox C, Gelinas C, Franzoso G. Regulation of the gadd45beta promoter by NF-kappaB. DNA Cell Biol 2002; 21:491-503.
[129]Jing A, Chen YM & Huang ZW. (2004) Critical Upstream Signals of Cytochrome c Release Induced by a Novel Bcl-2 Inhibitor J. Biol. Chem., 279(18), 19133-19140
[130]Judge AD, Sood V, Shaw JR, Fang D, McClintock K, and MacLachlan I. 2005. Sequence-dependentstimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol. 23: 457-462
[131]Kaltschmidt B, Kaltschmidt C, Hehner SP, Droge W, Schmitz ML. Repression of NF-kappaB impairs HeLa cell proliferation by functional interference with cell cycle checkpoint regulators. Oncogene 1999; 18:3213-25.
[132]Kamesaki H, Nishizawa K, Michaud GY, Cossman J, Kiyono T. TGF-beta 1 induces the cyclin-dependent kinase inhibitor p27Kip1 mRNA and protein in murine B cells. J Immunol 1998; 160:770-7.
[133]Kang H, Delong R, Fisher MH, and Juliano RL. 2005. Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides. Pharm. Res. 22:2099-2106.
[134]Kariko K, Bhuyan P, Capodici J, and Weissman D. 2004. Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3. J. Immunol. 172: 6545-6549.
[135]Kawakami S, Hattori Y, Lu Y, Higuchi Y, Yamashita F, and Hashida M. 2004. Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice. Pharmazie 59:405-408.
[136]Kawasaki H. and Taira K. 2003. Short hairpin type of dsRNAs that are controlled by tRNAVal promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells. Nucleic Acids Res. 31:700-707
[136]Kawasaki H, Suyama E, lyo M, and Taira K. 2003. siRNAs generated by recombinant human Dicer induce specific and significant but target site-independent gene silencing in human cells. Nucleic Acids Res. 31: 981-987.
[137]Keller M. 2005. Lipidic carriers of RNA/DNA oligonucleotides and polynucleotides: What a difference a formulation makes! J. Control. Release 103: 537-540.
[138]Khvorova A, Reynolds A, and Jayasena SD. 2003. Functional siRNAs and miRNAs exhibit strand bias. Cell 115: 209-216.
[139]Kim DH, Behlke MA., Rose SD, Chang MS, Choi S, and Rossi JJ. 2005a. Synthetic dsRNA Dicersubstrates enhance RNAi potency and efficacy. Nat. Biotechnol. 23:222-226.
[140]Kim DH, Longo M, Han Y, Lundberg P, Cantin E, and Rossi JJ. 2004. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat. Biotechnol. 22: 321-325.
[141]Kim EM, Jeong HJ, Park IK, Cho CS, Moon HB, Yu DY, Bom HS, Sohn MH, and Oh IJ. 2005b. Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): In vitro and in vivo studies. J. Control. Release 108:557-567.
[142]Kireeva ML, Lam SC, Lau LF. Adhesion of human umbilical vein endothelial cells to the immediate-early gene product Cyr61 is mediated through integrin alphavbeta3. J Biol Chem 1998; 273:3090-6.
[143]Kireeva ML, MO FE, Yang GP, Lau LF. Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion. Mol Cell Biol 1996; 16:1326-34.
[144]Kleemann R, Kapumiotu A, Frank RW, Gessner A, Mischke R, Flieger O, Juttner S, Brunner H, Bernhagen J.Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase.J Mol Biol. 1998 Jul 3;280(1):85-102.
[145]Kleemann R, Hausser A, Geiger G, Mischke R, Burger-Kentischer A, Flieger O, Johannes FJ, Roger T, Calandra T, Kapumiotu A, Grell M, Finkelmeier D, Brunner H, Bernhagen J. (2000) Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature. 408,211-216.
[146]Klein E, Ben-Bassat H, Neumann H, Ralph P, Zeuthen J, Polliack A, Vanky F. Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia. Int J Cancer. 1976 Oct 15;18(4):421-31.
[147]Klinge CM, Silver BF, Driscoll MD, Sathya G, Bambara RA, Hilf R. Chicken ovalbumin upstream promoter-transcription factor interacts with estrogen receptor, binds to estrogen response elements and half-sites, and inhibits estrogen-induced gene expression. J Biol Chem 1997; 272:31465-74.
[148]Koli K, Hyytiainen M, Ryynanen MJ, Keski-Oja J. Sequential deposition of latent TGF-beta binding proteins(LTBPs) during formation of the extracellular matrix in human lung fibroblasts. Exp Cell Res 2005; 310:370-82.
[149]Koli K, Wempe F, Stemer-Kock A, Kantola A, Komor M, Hofmann WK, von Melchner H, Keski-Oja J. Disruption of LTBP-4 function reduces TGF-beta activation and enhances BMP-4 signaling in the lung. J Cell Biol 2004; 167:123-33.
[150]Kong YZ, Yu X, Tang JJ, Ouyang X, Huang XR, Fingerle-Rowson G et al. Macrophage migration inhibitory factor induces MMP-9 expression: implications for destabilization of human atherosclerotic plaques. Atherosclerosis 2005; 178: 207- 15.
[151]Korenjak M, Taylor-Harding B, Binne UK, Satterlee JS, Stevaux O, Aasland R, White-Cooper H, Dyson N, Brehm A. Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Cell 2004; 119:181-93.
[152]Kraynack BA. and Baker BF. 2006. Small interfering RNAs containing full 2'-O-methylribonucleotide- modified sense strands display Argonaute2/elF2C2-dependent activity. RNA 12:163-176.
[153]Lan HY, Bacher M, Yang N, Mu W, Nikolic-Paterson DJ, Metz C et al. The pathogenic role of macrophage migration inhibitory factor in immunologically induced kidney disease in the rat. J Exp Med 1997; 185:1455- 65.
[154]Lan HY, Mu W, Yang NS, Meinhardt A, Nikolicpaterson DJ, Ng YY et al. De novo renal expression of macrophage migration inhibitory factor during the development of rat crescentic glomerulonephritis. Am J Pathol 1996:149:1119-27.
[155]Lan HY, Yang N, Metz C, Mu W, Song Q, Nikolic-Paterson DJ, Bacher M, Bucala R, Atkins RC.TNF-alpha up-regulates renal MIF expression in rat crescentic glomerulonephritis.Mol Med. 1997 Feb;3(2): 136-44.
[156]Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA, and Sullenger BA. 2004. In vivo activity of nuclease-resistant siRNAs. RNA 10: 766-771.
[157]Lee YS, Nakahara K, Pham JW. Kim K, He Z, Sontheimer EJ, and Carthew RW. 2004. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117:69-81.
[158]Leech M, Metz C, Bucala R, Morand EF. Regulation of macrophage migration inhibitory factor by endogenous glucocorticoids in rat adjuvant-induced arthritis. Arthritis Rheum. 2000 Apr;43(4):827-33
[159]Leech M, Metz CN, Smith M, Weedon H, Holdsworth SR, Bucala R et al. Macrophage migration inhibitory factor (MIF) in rheumatoid arthritis: evidence for pro-inflammatory function and regulation by glucocorticoids. Arthritis Rheum 1999; 42:1601- 8.
[160]Lehmann LE, Novender U, Schroeder S, Pietsch T, von Spiegel T, Putensen C, Hoeft A, Stuber F. Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis. Intensive Care Med. 2001 Aug;27(8):1412-5.
[161]Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A (2006) A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125: 987-1001.
[162]Lei K, & Davis RJ. (2003) JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc. Natl. Acad. Sci. USA. 100, 2432-2437
[163]Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R. MIF signal transduction initiated by binding to CD74. J Exp Med 2003; 197:1467-76.
[164]Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R. MIF signal transduction initiated by binding to CD74. J Exp Med. 2003 Jun 2;197(11): 1467-76
[165]Lesnik, E.A., Guinosso, C.J., Kawasaki, A.M., Sasmor, H., Zounes, M., Cummins, L.L., Ecker, D.J., Cook, P.D., and Freier, S.M. 1993. Oligodeoxynucieotides containing 2'-O-modified adenosine: Synthesis and effects on stability of DNA.RNA duplexes. Biochemistry 32: 7832-7838.
[166]Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, & Korsmeyer SJ. (2002) Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer herapeutics. Cancer Cell. 2, 183-192,
[167]Leuschner PJ, Ameres SL, Kueng S, and Martinez J. 2006. Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 7: 314-320.
[168]Lewis DL, Hagstrom JE, Loomis AG, Wolff JA, and Herweijer H. 2002. Efficient delivery of siRNA for inhibition of gene expression in postnatal mice. Nat. Genet. 32:107-108.
[169]Li L, Elledge SJ, Peterson CA, Bales ES, Legerski RJ. (1994) Specific association between the human DNA repair proteins XPA and ERCC1. Proc. Natl. Acad. Sci. USA, 91: 5012-5016.
[170]Li MJ, Bauer G, Michienzi A, Yee JK, Lee NS, Kim J, Li S, Castanotto D, Zaia J, and Rossi JJ. 2003. Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs. Mol. Ther. 8:196-206.
[171]Liao H, Bucala R, & Mitchell RA. (2003) Adhesion-dependent Signaling by Macrophage Migration Inhibitory Factor (MIF)* J. Biol. Chem. 278, 76-81
[172]Lin BR, Chang CC, Chen LR, Wu MH, Wang MY, Kuo IH, Chu CY, Chang KJ, Lee PH, Chen WJ, Kuo ML, Lin MT. Cysteine-rich 61 (CCN1) enhances chemotactic migration, transendothelial cell migration, and intravasation by concomitantly up-regulating chemokine receptor 1 and 2. Mol Cancer Res 2007;5:1111-23
[173]Lin MT, Chang CC, Chen ST, Chang HL, Su JL, Chau YP, Kuo ML. Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation. J Biol Chem 2004; 279:24015-23.
[174]Linke SP, Clarkin KC, Di Leonardo A, Tsou A, Wahl GM. A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev 1996; 10:934-47.
[175]LinksKim KS, Seu YB, Baek SH, Kim MJ, Kim KJ, Kim JH, Kim JR. Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism. Mol Biol Cell 2007; 18:4543-52.
[176]Liu JW, Chandra D, Tang SH, Chopra D, Tang DGIdentification and characterization of Bimgamma, anovel proapoptotic BH3-only splice variant of Bim.Cancer Res. 2002 May 15;62(10):2976-81
[177]Liu L, Chen J, Zhang J, Ji C, Zhang X, Gu S, Xie Y, Mao Y. Overexpression of BimSs3, the novel isoform of Bim, can trigger cell apoptosis by inducing cytochrome c release from mitochondria. Acta Biochim Pol. 2007;54(3):603-10.
[178]Liu CM, Liu DP, Dong WJ, and Liang CC. 2004a. Retrovirus vector-mediated stable gene silencing in human cell. Biochem. Biophys. Res. Commun. 313: 716-720.
[179]Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, and Hannon GJ. 2004b. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437-1441.
[180]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25:402-8.
[181]Lue H, Kapumiotu A, Fingerle-Rowson G, Roger T, Leng L, Thiele M, Calandra T, Bucala R, Bernhagen J. Rapid and transient activation of the ERK MAPK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on JAB1/CSN5 and Src kinase activity. Cell Signal 2006; 18:688-703.
[182]Mahat, R.I., Monera, O.D., Smith, L.C., and Rolland, A. 1999. Peptide-based gene delivery. Curr. Opin. Mol. Ther. 1:226-243.
[183]Mahato, R.I., Cheng, K., and Guntaka, R.V. 2005. Modulation of gene expression by antisense and antigene oligodeoxynucleotides and small interfering RNA. Expert Opin. Drug Deliv. 2: 3-28.
[184]Makita, H. et al. Effect of anti-macrophage migration inhibitory factor antibody on lipopolysaccharide-induced pulmonary neutrophil accumulation. Am. J. Respir. Crit. Care Med. 158, 573-579 (1998).
[185]Manoharan M. 2004. RNA interference and chemically modified small interfering RNAs. Curr. Opin. Chem. Biol. 8: 570-579.
[186]Marani M, Tenev T, Hancock D, Downward J, Lemoine NR.Identification of novel isoforms of the BH3domain protein Bim which directly activate Bax to trigger apoptosis.Mol Cell Biol. 2002 Jun;22(11):3577-89.
[187]Marshall, W.S. and Kaiser, R.J. 2004. Recent advances in the high-speed solid phase synthesis of RNA. Curr. Opin. Chem. Biol. 8: 222-229.
[188]Marson AL, Tarr DE, Scott AL. Macrophage migration inhibitory factor (mif) transcription is significantly elevated in Caenorhabditis elegans dauer larvae. Gene. 2001 Oct 31;278(1-2):53-62.
[189]Massague J. G1 cell-cycle control and cancer. Nature 2004; 432:298-306.
[190]Matranga C, Tomari Y, Shin C, Bartel DP, and Zamore PD. 2005. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123: 607-620.
[191]Matsukura, S., Jones, PA, and Takai, D. 2003. Establishment of conditional vectors for hairpin siRNA knockdowns. Nucleic Acids Res. 31: e77.
[192]McCaffrey, A.P., Meuse, L., Pham, T.T., Conklin, D.S., Hannon, G.J., and Kay, M.A. 2002. RNA interference in adult mice. Nature 418:38-39.
[193]McNamara II, J.O., Andrechek, E.R., Wang, Y., Viles, K.D., Rempel, R.E., Gilboa, E., Sullenger, B.A., and Giangrande, P.H. 2006. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat. Biotechnol. 24: 1005-1015
[193]Meister, G. and Tuschl, T. 2004. Mechanisms of gene silencing by double-stranded RNA. Nature 431: 343-349
[194]Meister, G., Landthaler, M., Patkaniowska, A., Dorsett, Y., Teng, G., and Tuschl, T. 2004. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol. Cell 15:185-197.
[195]Menendez JA, Vellon L, Mehmi I, Teng PK, Griggs DW, Lupu R. A novel CYR61-triggered 'CYR61-alphavbeta3 integrin loop' regulates breast cancer cell survival and chemosensitivity through activation of ERK1/ERK2 MAPK signaling pathway. Oncogene 2005; 24:761-79.
[196]Merdan, T., Callahan, J., Petersen, H., Kunath, K., Bakowsky, U., Kopeckova, P., Kissel, T., and Kopecek, J. 2003. Pegylated polyethylenimine-Fab' antibody fragment conjugates for targeted gene delivery to humanovarian carcinoma cells. Bioconjug. Chem. 14:989-996.
[197]Meyer-Siegler KL, Leifheit EC, Vera PL. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells. BMC Cancer 2004;4:34.
[198]Milligan JF. and Uhlenbeck OC. 1989. Synthesis of small RNAs using T7 RNA polymerase. Methods Enzymol. 180: 51-62.
[199]Mitchell RA, Liao H, Chesney J, Fingerie-Rowson G, Baugh J, David J, Bucala R. Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response. Proc Natl Acad Sci U S A 2002; 99:345-350.
[200]Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase (MAPK) andcytoplasmic phospholipase A2 activation by macrophage migration inhibitory factor (MIF). Regulatory role in cell proliferation and glucocorticoid action. J Biol Chem. 1999 Jun 18;274(25): 18100-6.
[201]Mitchell RA. Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal 2004; 16:13-9.
[202]Mitchell RA, Liao H, Chesney J, Fingerie-Rowson G, Baugh J, David J, Bucala R. (2002) Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response.Proc Natl Acad Sci U S A. 99(1),345-350.
[203]Mittelstadt PR, Ashwell JD. Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ. J Biol Chem 2001;276:29603-10.
[204]Mizue Y, Nishihira J, Miyazaki T, Fujiwara S, Chida M, Nakamura K et al. Quantitation of macrophage migration inhibitory factor (MIF) using the one-step sandwich enzyme immunosorbent assay: elevated serum MIF concentrations in patients with autoimmune diseases and identification of MIF in erythrocytes. Int J Mol Med 2000; 5: 397-403.
[205]Morand EF, Leech M, Weedon H, Metz C, Bucala R, Smith MD. Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations. Rheumatology (Oxford) 2002; 41:558- 62.
[206]Morand EF. New therapeutic target in inflammatory disease: macrophage migration inhibitory factor. Intern Med J 2005; 35:419-26.
[207]Moreau C, Cartron PF, Hunt A, Mefiah K, Green DR, Evan G, Vallette FM, Juin P. (2003)Minimal BH3 peptides promote cell death by antagonizing anti-apoptotic proteins. J Biol Chem. 278,19426-19435
[208]Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, Dickinson B, McSwiggen JA, Vargeese C,Bowman K, Shaffer CS, et al. 2005a. Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41:1349-1356.
[209]Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, Hartsough K, Machemer L, Radka S., Jadhav V., et al. 2005b. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23:1002-1007.
[210]Mosmann T 1983 Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55-63
[211]Mufioz NM, Upton M, Rojas A, Washington MK, Lin L, Chytil A, Sozmen EG, Madison BB, Pozzi A, Moon RT, Moses HL, Grady WM. Transforming growth factor beta receptor type II Inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation. Cancer Res. 2006; 66:9837-44.
[212]Murakami H, Akbar SM, Matsui H, Onji M . Macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis: clinical implications and pathogenic significance. Eur J Clin Invest 2001; 31: 337-43.
[213]Myers JW, Jones JT, Meyer T, and Ferrell Jr JE. 2003. Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing. Nat. Biotechnol. 21:324-328.
[214]Naito Y, Yamada T, Ui-Tei K, Morishita S, and Saigo K. 2004. siDirect Highly effective, target-specific siRNA design software for mammalian RNA interference. Nucleic Acids Res. 32: W124-W129.
[215]Nemajerova A, Moll UM, Petrenko O, Fingerle-Rowson G. Macrophage migration inhibitory factor coordinates DNA damage response with the proteasomal control of the cell cycle. Cell Cycle 2007; 6:1030-4.
[216]Nguyen MT, Lue H, Kleemann R, Thiele M, Tolle G, Finkelmeier D, Wagner E, Braun A, Bemhagen J. The cytokine macrophage migration inhibitory factor reduces pro-oxidative stress-induced apoptosis. J Immunol 2003:170:3337-47.
[217]Niino M, Ogata A, Kikuchi S, Tashiro K, Nishihira J . Macrophage migration inhibitory factor in thecerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Behcet's disease. J Neurol Sci 2000; 179:127- 31.
[218]Nishihira J, Ishibashi T, Fukushima T, Sun B, Sato Y, Todo S. Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis. Ann N Y Acad Sci. 2003 May;995:171-82.Nishihira, J.(2000) Macrophage migration inhibitory factor (MIF): Its essential role in the immune system and cell growth. J Interferon Cytokine Res. 20,751-762
[219]Nishitani H, Taraviras S, Lygerou Z, Nishimoto T. The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase. J Biol Chem 2001; 276:44905-11.
[219]Nishitsuji H, Kohara M, Kannagi M, and Masuda T. 2006. Effective suppression of humanimmunodeficiency virus type 1 through a combination of short- or long-hairpin RNAs targeting essential sequences for retroviral integration. J. Virol. 80: 7658-7666.
[220]No D, Yao TP, and Evans RM. 1996. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc. Natl. Acad. Sci. 93: 3346-3351.
[221]Norris JL, Baldwin AS Jr. Oncogenic Ras enhances NF-kappaB transcriptional activity through Raf-dependent and Raf-independent mitogen-activated protein kinase signaling pathways. J Biol Chem 1999; 274:13841-6.
[222]Nykanen, A., Haley, B., and Zamore, P.D. 2001. ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107: 309-321.
[223]Obaya AJ, Mateyak MK, Sedivy JM.Mysterious liaisons: the relationship between c-Myc and the cell cycle. Oncogene 1999; 18:2934-41.
[224]O'Connor, L., Strasser, A., O'Reilly, L.A., Hausmann, G., Adams, J.M., Cory, S., Huang, D.C.(1998) Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 17(2), 384-395.
[225]Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG. Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. J Biol Chem 1996; 271:30322-5.
[226]Ohkawa J. and Taira K. 2000. Control of the functional activity of an antisense RNA by a tetracycline-responsive derivative of the human U6 snRNA promoter. Hum. Gene Ther. 11:577-585.
[227]Ohkawara T, Nishihira J, Takeda H, Hige S, Kato M, Sugiyama T et al. Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice. Gastroenterology 2002; 123:256-70.
[228]Onodera S, Kaneda K, Mizue Y, Koyama Y, Fujinaga M, Nishihira J . Macrophage migration inhibitory factor up-regulates expression of matrix metalloproteinases in synovial fibroblasts of rheumatoid arthritis. J Biol Chem 2000; 275: 444- 50.
[229]Onodera S, Nishihira J, Iwabuchi K, Koyama Y, Yoshida K, Tanaka S, Minami A. Macrophage migration inhibitory factor up-regulates matrix metalloproteinase-9 and -13 in rat osteoblasts. Relevance to intracellular signaling pathways. J Biol Chem. 2002 Mar 8;277(10):7865-74.
[230]Onodera S, Nishihira J, Koyama Y, Majima T, Aoki Y, Ichiyama H et al. Macrophage migration inhibitory factor up-regulates the expression of interleukin-8 messenger RNA in synovial fibroblasts of rheumatoid arthritis patients: common transcriptional regulatory mechanism between interleukin-8 and interleukin-1 beta. Arthritis Rheum 2004; 50:1437-47.
[231]Onodera S, Suzuki K, Matsuno T, Kaneda K, Takagi M, Nishihira J. Macrophage migration inhibitory factor induces phagocytosis of foreign particles by macrophages in autocrine and paracrine fashion. Immunology 1997; 92:131-7.
[232]Onodera S, Tanji H, Suzuki K, Kaneda K, Mizue Y, Sagawa A, Nishihira J.High expression of macrophage migration inhibitory factor in the synovial tissues of rheumatoid joints.Cytokine. 1999 Feb;11(2): 163-7.
[233]Osterhout JL, Waheed AA, Hiol A, Ward RJ, Davey PC, Nini L, Wang J, Milligan G, Jones TL, Druey KM. Palmitoylation regulates regulator of G-protein signaling (RGS) 16 function. II. Palmitoylation of a cysteine residue in the RGS box is critical for RGS16 GTPase accelerating activity and regulation of Gi-coupled signalling. J Biol Chem 2003; 278:19309-16.
[234]Paddison, P.J., Caudy, A.A., Bernstein, E., Hannon, G.J., and Conklin, D.S. 2002. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes & Dev. 16: 948-958.
[235]Pan JH, Sukhova GK, Yang JT, Wang B, Xie T, Fu H et al. Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 2004; 109: 3149-53.
[236]Paul CP, Good PD, Winer I, and Engelke DR. 2002. Effective expression of small interfering RNA in human cells. Nat. Biotechnol. 20: 505-508.
[237]Pelengaris S, Khan M, Evan G. C-MYC: more than just a matter of life and death. Nat Rev Cancer 2002; 2:764-76.
[238]Perez-Roger I, Kim SH, Griffiths B, Sewing A, Land H. Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1). EMBO J 1999 Oct 1;18(19):5310-20.
[239]Persengiev SP, Zhu X, and Green MR. 2004. Nonspecific, concentration-dependent stimulation andrepression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 10:12-18.
[240]Petrenko O, Moll UM. Macrophage migration inhibitory factor MIF interferes with the Rb-E2F pathway. Mol Cell 2005; 17(2):225-36.
[241]Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S, Yaniv M. Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell 1994; 76:747-60.
[242]Piva R, Belardo G, Santoro MG. NF-kappaB: a stress-regulated switch for cell survival. Antioxid Redox Signal 2006; 8:478-86.
[243]Potten CS, Booth D, Haley JD. Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo. Br J Cancer 1997; 75:1454-9.
[244]Prall OW, Sarcevic B, Musgrove EA, Watts CK, Sutherland RL. Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J Biol Chem 1997; 272:10882-94.
[245]Pulverer BJ, Hughes K, Franklin CC, Kraft AS, Leevers SJ, Woodgett JR. Co-purification of mitogen-activated protein kinases with phorbol ester-induced c-Jun kinase activity in U937 leukaemic cells. Oncogene 1993; 8:407-15.
[246]Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR. Phosphorylation of c-jun mediated by MAP kinases. Nature 1991; 353:670-4.
[247]Putcha GV, Harris CA, Moulder KL, Easton RM, Thompson CB, Johnson EM Jr. (2002) Intrinsic and Extrinsic Pathway Signaling during Neuronal Apoptosis: Lessons from the Analysis of Mutant Mice. J Cell Biol. 157(3), 441-53
[248]Puthalakath H, Huang DC, O'Reilly LA, King SM, & Strasser A. (1999) The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell 3,287-296
[249]Rathmell JC, & Thompson CB.(2002) Pathways of Apoptosis in Lymphocyte Development, Homeostasis, and Disease. Cell. 109,97-107
[250]Ravitz MJ, Wenner CE. Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-beta. Adv Cancer Res 1997; 71:165-207.
[251]Ren Y, Chan HM, Fan J, Xie Y, Chen YX, Li W, Jiang GP, Liu Q, Meinhardt A, Tam PK. Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma. Oncogene. 2006 Jun 15;25(25):3501-8.
[252]Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, Wong J.Macrophage migration inhibitory factorstimulates angiogenic factor expression and correlates with differentiation and lymph node status in patients with esophageal squamous cell carcinoma. Ann Surg. 2005 Jul;242(1):55-63.
[253]Ren Y, Tsui HT, Poon RT, Ng IO, Li Z, Chen Y, Jiang G, Lau C, Yu WC, Bacher M, Fan ST. Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma. Int J Cancer. 2003 Oct 20;107(1 ):22-9.
[254]Reynisdottir I, Polyak K, lavarone A, Massague J. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev 1995; 9:1831-45.
[255]Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, and Khvorova A. 2004. Rational siRNA design for RNA interference. Nat. Biotechnol. 22:326-330.
[256]Roger T, David J, Glauser MP, Calandra T.MIF regulates innate immune responses through modulation of Toll-like receptor 4.Nature. 2001 Dec 20-27;414(6866):920-4
[257]Roger T, Froidevaux C, Martin C, Calandra T.Macrophage migration inhibitory factor (MIF) regulates host responses to endotoxin through modulation of Toll-like receptor 4 (TLR4).J Endotoxin Res. 2003;9(2):119-23.
[258]Rosengren E, Aman P, Thelin S, Hansson C, Ahlfors S, Bjork P, Jacobsson L, Rorsman H. The macrophage migration inhibitory factor MIF is a phenylpyruvate tautomerase.FEBS Lett. 1997 Nov 3;417(1):85-8.
[259]Rosengren E, Bucala R, Aman P, Jacobsson L, Odh G, Metz CN, Rorsman H. The immunoregulatory mediator macrophage migration inhibitory factor (MIF) catalyzes a tautomerization reaction.Mol Med. 1996 Jan;2(1):143-9.
[260]Ruan W, Xu E, Xu F, Ma Y, Deng H, Huang Q, Lv B, Hu H, Lin J, Cui J, Di M, Dong J, Lai M. IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis. Cancer Biol Ther 2007; 6:354-9.
[261)Ruaro EM, Collavin L, Del Sal G, Haffner R, Oren M, Levine AJ, Schneider C. A proline-rich motif in p53 is required for transactivation-independent growth arrest as induced by Gas1. Proc Natl Acad Sci U S A 1997; 94:4675-80.
[262]Rubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J, Rooney DL, Ihrig MM, McManus MT, Gertler FB, et al. 2003. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat. Genet. 33:401-406.
[263]Saharinen J, Taipale J, Monni O, Keski-Oja J. Identification and characterization of a new latent transforming growth factor-beta-binding protein, LTBP-4. J Biol Chem 1998; 273:18459-69.
[264]Sampey AV, Hall PH, Mitchell RA, Metz CN, Morand EF . Regulation of synoviocyte phospholipase A2 and cyclooxygenase 2 by macrophage migration inhibitory factor. Arthritis Rheum 2001; 44:1273- 80.
[265]Santhakumaran LM, Thomas T, and Thomas TJ. 2004. Enhanced cellular uptake of a triplex-forming oligonucleotide by nanoparticle formation in the presence of polypropylenimine dendrimers. Nucleic Acids Res. 32:2102-2112.
[266]Santos L, Lacey DC, Yang Y, Leech M, Morand EF . Activation of synovial cell p38 MAP kinase by macrophage migration inhibitory factor (MIF). J Rheumatol 2004; 31:1038- 43.
[267]Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS,Minn AJ. et al. (1997). Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.Science 275,983 -986.
[268]Schepers U. 2005. RNA interference in practice: Principles, basics, and methods for gene silencing in C. elegans, Drosophila, and mammals , Wiley-VCH, New York.
[269]Schmidt M, Fernandez de Mattos S, van der Horst A, Klompmaker R, Kops GJ, Lam EW, Burgering BM, Medema RH. Cell cycle inhibition by FoxO forkhead transcription factors involves downregulation of cyclin D.Mol Cell Biol 2002; 22:7842-52.
[270]Schober A, Bernhagen J, Thiele M, Zeiffer U, Knarren S, Roller M et al. Stabilization of atherosclerotic plaques by blockade of macrophage migration inhibitory factor after vascular injury in apolipoprotein E-deficient mice. Circulation 2004; 109: 380- 85.
[271]Schomber T, Kalberer CP, Wodnar-Filipowicz A, and Skoda RC. 2004. Gene silencing by lentivirus- mediated delivery of siRNA in human CD34+ cells. Blood 103:4511-4513.
[272]Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, and Zamore PD. 2003. Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199-208.
[273]Scott DK, Mitchell JA, Granner DK. The orphan receptor COUP-TF binds to a third glucocorticoid accessory factor element within the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem 1996;271:31909-14.
[274]Semizarov D, Frost L, Sarthy A, Kroeger P, Halbert DN, and Fesik SW. 2003. Specificity of short interfering RNA determined through gene expression signatures. Proc. Natl. Acad. Sci. 100:6347-6352.
[275]Shand JH, Beattie J, Song H, Phillips K, Kelly SM, Flint DJ, Allan GJ. Specific amino acid substitutionsdetermine the differential contribution of the N- and C-terminal domains of insulin-like growth factor (IGF)-binding protein-5 in binding IGF-I. J Biol Chem 2003; 278:17859-66.
[276]Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002; 4:E131-6.
[277]Shimizu T, Nishihira J, Mizue Y, Nakamura H, Abe R, Watanabe H et al. High macrophage migration inhibitory factor (MIF) serum levels associated with extended psoriasis. J Invest Dermatol 2001; 116:989- 90..
[278]Siolas D, Lemer C, Burchard J, Ge W, Linsley PS, Paddison PJ, Hannon GJ, and Cleary MA. 2005. Synthetic shRNAs as potent RNAi triggers. Nat. Biotechnol. 23:227-231.
[279]Sioud M. 2004. Therapeutic siRNAs. Trends Pharmacol. Sci. 25:22-28.
[280]Sioud M. 2005. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J. Mol. Biol. 348: 1079-1090.
[281]Sioud M. 2006. Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: A central role for 2'-hydroxyl uridines in immune responses. Eur. J. Immunol. 36: 1222-1230.
[282]Sohail M, Doran G, Riedemann J, Macaulay V, and Southern EM. 2003. A simple and cost-effective method for producing small interfering RNAs with high efficacy. Nucleic Acids Res. 31: e38.
[283]Song E, Lee SK, Dykxhoorn DM, Novina C, Zhang D, Crawford K, Cerny J, Sharp PA, Lieberman J, Manjunath N, Shankar P. 2003a. Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages. J. Virol. 77: 7174-7181.
[284]Song E, Lee SK, Wang J, Ince N, Ouyang N, Min J, Chen J, Shankar P, Lieberman J. 2003b. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat. Med. 9:347-351.
[285]Song E, Zhu P, Lee SK, Chowdhury D, Kussman S, Dykxhoom DM, Feng Y, Palliser D, Weiner DB, Shankar P, Marasco WA, Lieberman J. 2005. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat. Biotechnol. 23: 709-717.
[286]Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Moroy T, Bartek J, Massague J, Hanel F,
[287]Eilers M. Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol 2001; 3:392-9.
[288]Steinhoff M, Meinhardt A, Steinhoff A, Gemsa D, Bucala R, Bacher M . Evidence for a role of macrophage migration inhibitory factor in psoriatic skin disease. Br J Dermatol 1999; 141:1061-6.
[289]Su B, Karin M. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr Opin Immunol 1996; 8:402-11.
[290]Subramanya HS, Roper DI, Dauter D, Dodson EJ, Davies GJ, Wilson KS and Wigley DB (1996) Enzymaticketonization of 2-hydroxymuconate: specificity and mechanism investigated by the crystal structures of two isomerases. Biochemistry, 35,792-802
[291]Sugimoto H, Taniguchi M, Nakagawa A, Tanaka I, Suzuki M, Nishihira J.Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1.54 A resolution.Biochemistry. 1999 Mar 16;38(11):3268-79
[292]Sun B, Nishihira J, Yoshiki T, Kondo M, Sato Y, Sasaki F, Todo S. Macrophage migration inhibitory factor promotes tumor invasion and metastasis via the Rho-dependent pathway. Clin Cancer Res. 2005 Feb 1;11(3):1050-8.
[293]Sun HW, Bernhagen J, Bucala R, Lolis E.Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor.Proc Natl Acad Sci U S A. 1996 May 28;93(11):5191-6.
[294]Sun L, Chen C. Expression of transforming growth factor beta type III receptor suppresses tumorigenicity of human breast cancer MDA-MB-231 cells. J Biol Chem 1997; 272:25367-72.
[295]Sun B, Nishihira J, Suzuki M, Fukushima N, Ishibashi T, Kondo M, Sato Y, Todo S. (2003) Induction of macrophage migration inhibitory factor by lysophosphatidic acid: relevance to tumor growth and angiogenesis..Int J Mol Med. 12(4), 633-641.
[296] Suzuki M, Sugimoto H, Nakagawa A, Tanaka I, Nishihira J, Sakai M.Crystal structure of the macrophage migration inhibitory factor from rat liver.Nat Struct Biol. 1996 Mar;3(3):259-66.
[297]Swant JD, Rendon BE, Symons M, Mitchell RA. (2005) Rho GTPase-dependent Signaling Is Required for Macrophage Migration Inhibitory Factor-mediated Expression of Cyclin D1. J. Biol. Chem. 280,23066-23072
[298]Swant JD, Rendon BE, Symons M, Mitchell RA. Rho GTPase-dependent signaling is required for macrophage migration inhibitory factor-mediated expression of cyclin D1. J Biol Chem 2005; 280:23066-72.
[299]Swope MD, Lolis E. Macrophage migration inhibitory factor cytokine, hormone, or enzyme? Rev Physiol Biochem Pharmacol. 1999;139:1-32.
[300TTakekawa M, Saito H. A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell 1998; 95:521-30.
[301]Talos F, Mena P, Fingerle-Rowson G, Moll U, Petrenko O.MIF loss impairs Myc-induced lymphomagenesis. Cell Death Differ. 2005 Oct;12(10):1319-28
[302]Taniguchi Y, Yorioka N, Yamashita K, Masaki T, Yamakido M . Macrophage migration inhibitory factor in IgA nephropathy. Kidney Int 1998; 54:2245- 6.
[303]Tiscomia G, Singer O, Ikawa M, and Verma IM. 2003. A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA. Proc. Natl. Acad. Sci. 100:1844-1848.
[304]Toh ML, Aeberll D, Lacey D, Yang Y, Santos LL, Clarkson M, Sharma L, Clyne C, Morand EF. Regulation of IL-1 and TNF receptor expression and function by endogenous macrophage migration inhibitory factor. J Immunol. 2006 Oct 1;177(7):4818-25.
[305]Truhlar SM, Torpey JW, Komives EA. Regions of IkappaBalpha that are critical for its inhibition of NF-kappaB.DNA interaction fold upon binding to NF-kappaB. Proc Natl Acad Sci U S A 2006; 103:18951-6.
[306]Tsuneoka M, Teye K, Arima N, Soejima M, Otera H, Ohashi K, Koga Y, Fujita H, Shirouzu K, Kimura H,Koda Y. A novel Myc-target gene, mimitin, that is involved in cell proliferation of esophageal squamous cell carcinoma. J Biol Chem 2005; 280:19977-85.
[307]U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001 Nov 30;509(1):135-41
[308]Ui-Tei, K., Naito, Y., Takahashi, F., Haraguchi, T., Ohki-Hamazaki, H., Juni, A., Ueda, R., and Saigo, K. 2004. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res. 32: 936-948.
[309]Van Craenenbroeck, K., Vanhoenacker, P., Leysen, J.E., and Haegeman, G. 2001. Evaluation of the tetracycline- and ecdysone-inducible systems for expression of neurotransmitter receptors in mammalian cells. Eur. J. Neurosci. 14: 968-976.
[310]Van Der Heide LP, Hoekman MF, Smidt MP. The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation. Biochem J 2004; 380:297-309.
[311]Van Kuilenburg AB, Van Beeumen JJ, Demol H, Van den Bogert C, Schouten I, Muijsers AO. Subunit IV of human cytochrome c oxidase, polymorphism and a putative isoform. Biochim Biophys Acta. 1992 Feb 26;1119(2):218-24.
[312]Van Waes C. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res 2007; 13:1076-82.
[313]Vlach J, Hennecke S, Alevizopoulos K, Conti D, Amati B. Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c-Myc. EMBO J 1996 Dec 2;15(23):6595-604.
[314]Weiser WY, Temple PA, Witek-Giannotti JS, Remold HG, Clark SC, David JR. Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor.Proc Natl Acad Sci U S A. 1989 Oct;86(19):7522-6.
[315]Welford SM, Bedogni B, Gradin K, Poellinger L, Broome Powell M, Giaccia AJ. HIF1alpha delays premature senescence through the activation of MIF. Genes Dev 2006;20:3366-71.
[316]Welford SM, Bedogni B, Gradin K, Poellinger L, Powell MB, & Giaccia AJ. (2006) HIF1 delays premature senescence through the activation of MIF.Gene Dev.20,3366-3371
[317]White ES,Flaherty KR,Carskadon S,Brant A,lannettoni MD,Yee J,Orringer MB,Arenberg DA.Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer,role in angiogenesis and prognosis.Clin Cancer Res.2003 Feb;9(2):853-60
[318]Whitmarsh A J,Davis RJ.Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways.J Mol Med 1996;74:589-607.
[319]Wilson JM,Coletta PL,Cuthbert R J,Scott N,MacLennan K,Hawcroft G,Leng L,Lubetsky JB,Jin KK,Lolis E,Medina F,Brieva JA,Poulsom R,Markham AF,Bucala R,Hull MA.Macrophage migration inhibitory factor promotes intestinal tumorigenesis.Gastroenterology.2005 Nov;129(5):1485-503
[320]Wiznerowicz M.and Trono D.2003.Conditional suppression of cellular genes:Lentivirus vector-mediated drug-inducible RNA interference.J.Virol.77:8957-8961.
[321]Wohlschlegel JA,Dwyer BT,Dhar SK,Cvetic C,Walter JC,Dutta A.Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.Science 2000;290:2309-12.
[322]Wong LF,Ralph GS,Walmsley LE,Bienemann AS,Parham S,Kingsman SM,Uney JB,Mazarakis ND.2005.Lentiviral-mediated delivery of Bcl-2 or GDNF protects against excitotoxicity in the rat hippocampus.Mol.Ther.11:89-95.
[323]Wooddell Cl,Van Hout CV,Reppen T,Lewis DL,and Herweijer H.2005.Long-term RNA interference from optimized siRNA expression constructs in adult mice.Biochem.Biophys.Res.Commun.334:117-127.
[324]Wu X,Li Y,Crise B,and Burgess SM.2003.Transcription start regions in the human genome are favored targets for MLV integration.Science 300:1749-1751
[325]Xia H,Mao Q,Paulson HL,and Davidson BL.2002.siRNA-mediated gene silencing in vitro and in vivo.Nat.Biotechnol.20:1006-1010.
[326]Xie D,Yin D,Tong X,O'Kelly J,Mori A,Miller C,Black K,Gui D,Said JW,Koeffler HP.Cyr61 is overexpressed in gliomas and involved in integrin-linked kinase-mediated Akt and beta-catenin-TCF/Lef signaling pathways.Cancer Res 2004;64:1987-96.
[327]Yang BS,Hauser CA,Henkel G,Colman MS,Van Beveren C,Stacey KJ,Hume DA,Maki RA,Ostrowski MC.Ras-medlated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2.Mol Cell Biol 1996;16:538-47.
[328]Yang D,Buchholz F,Huang Z,Goga A,Chen CY,Brodsky FM,Bishop JM.2002.Shod RNA duplexes produced by hydrolysla with Eschedchia coli RNase Ⅲ mediate effective RNA interference in mammalian cells. Proc. Natl. Acad. Sci. 99: 9942-9947.
[329]Ye Z, Cheng K, Guntaka RV, and Mahato RI. 2005. Targeted delivery of a triplex-forming oligonucleotide to hepatic stellate cells. Biochemistry 44:4466-4476
[330]Yoshida Y, Tanaka S, Umemori H, Minowa O, Usui M, Ikematsu N, Hosoda E, Imamura T, Kuno J, Yamashita T, Miyazono K, Noda M, Noda T, Yamamoto T. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell 2000; 103:1085-97.
[331]Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 2000; 92:1472-89.
[332]Yuan B, Latek R, Hossbach M, Tuschl T, and Lewitter F. 2004. siRNA Selection Server: An automated siRNA oligonucleotide prediction server. Nucleic Acids Res. 32: W130-W134.
[333]Yudin AI, Goldberg E, Robertson KR, Overstreet JW. Calpain and calpastatin are located between the plasma membrane and outer acrosomal membrane of cynomolgus macaque spermatozoa. J Androl. 2000 Sep-Oct;21(5):721-9
[334]Zamore, P.D. and Haley, B. 2005. Ribo-gnome: The big world of small RNAs. Science 309:1519-1524.
[335]Zhang Y, Neo SY, Han J, Yaw LP, Lin SC. RGS16 attenuates galphaq-dependent p38 mitogen-activated protein kinase activation by platelet-activating factor. J Biol Chem 1999; 274:2851-7.
[336]Zhang, C., Tang, N., Liu, X., Liang, W., Xu, W., and Torchilin, V.P. 2006. siRNA-containing liposomes modified with polyarginine effectively silence the targeted gene. J. Control. Release 112:229-239
[2]Abe Y,Matsumoto S,Wei S,Nezu K,Miyoshi A,Kito K,Ueda N,Shigemoto K,Hitsumoto Y,Nikawa J,Enomoto Y.Cloning and characterization of a p53-related protein Idnase expressed in intedeukin-2-activated cytotoxic T-cells,epithelial tumor cell lines,and the testes.J Biol Chem 2001;276:44003-11.
[3]Adachi,M.,Zhao,X.,Imai,K.(2005) Nomenclature of dynein light chain-linked BH3-only protein Bim isoforms.Cell Death Differ.12,192-193
[4]Adams,J.M.,& Cory,S.(1998) The Bcl-2 protein family:Arbiters of cell survival.Science.281,1322-1326
[5]Allan G J,Tonner E,Szymanowska M,Shand JH,Kelly SM,Phillips K,Clegg RA,Gow IF,Beattie J,Flint DJ.Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor(IGF)-binding protein-5 results in progressive loss of both IGF-Ⅰ binding and inhibition of IGF-Ⅰ biological action.Endocrinology 2006;147:338-49.
[6]Amarasinghe AK,Calin-Jageman I.,Harmouch,A.,Sun,W.,and Nicholson,A.W.2001.Escherichia coli ribonuclease Ⅲ:Affinity purification of hexahistidine-tagged enzyme and assays for substrate binding and cleavage.Methods Enzymol.342:143-158.
[7]Amarzguioui M,Holen T,Babaie E,and Prydz H.2003.Tolerance for mutations and chemical modifications in a siRNA.Nucleic Acids Res.31:589-595.
[8]Amarzguioui M,Rossi J J,and Kim D.2005.Approaches for chemically synthesized siRNA and vector-mediated RNAi.FEBS Lett.579:5974-5981.
[9]Amati B.Integrating Myc and TGF-beta signalling in cell-cycle control.Nat Cell Biol.2001;3:E112-3.
[10]Arai K,Maruyama Y,Nishida M,Tanabe S,Takagahara S,Kozasa T,Mori Y,Nagao T,Kurose H.Differential requirement of G alpha12,G alpha13,G alphaq,and G beta gamma for endothelinol-induced c-Jun NH2-terminal kinase and extracellular signal-regulated kinase activation.Mol Pharmacol 2003;63:478-88.
[11]Attwooll C,Lazzerini Denchi E,Helin K.The E2F family:specific functions and overlapping interests.EMBO J 2004;23:4709-16.
[12]Ayroldi E,Migliorati G,Bruscoli S,Marchetti C,Zollo O,Cannarile L,D'Adamio F,Riccardi C.Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB.Blood 2001;98:743-53.
[13]Ayroldi E,Zollo O,Macchiarulo A,Di Marco B,Marchetti C,Riccardi C.Glucocorticoid-induced leucine zipper inhibits the Raf-extracellular signal-regulated kinase pathway by binding to Raf-1.Mol Cell Biol 2002;22:7929-41.
[14]Bacher M,Metz CN,Calandra T,Mayer K,Chesney J,Lohoff M,Gemsa D,Donnelly T,Bucala R.An essential regulatory role for macrophage migration inhibitory factor in T-cell activation.Proc Natl Acad Sci U S A.1996 Jul 23;93(15):7849-54.
[15]Baeuerle PA,Baltimore D.I kappa B:a specific inhibitor of the NF-kappa B transcription factor.Science 1988;242:540-6.
[16]Baldwin AS Jr,Azizkhan JC,Jensen DE,Beg AA,Coodly LR.Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts. Mol Cell Biol 1991; 11:4943-51.
[17]Bartel DP. 2004. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116:281-297.
[18]Baumann B, Weber CK, Troppmair J, Whiteside S, Israel A, Rapp UR, Wirth T. Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation. Proc Natl Acad Sci U S A 2000; 97:4615-20.
[19]Baumann R, Casaulta C, Simon D, Conus S, Yousefi S, Simon HU. (2003) Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway. FASEB J. 17(15), 2221-2230.
[20]Beattie J, Allan GJ, Lochrie JD, Flint DJ. Insulin-like growth factor-binding protein-5 (IGFBP-5): a critical member of the IGF axis. Biochem J 2006; 395:1-19.
[21]Beishuizen A, Thijs LG, Haanen C, Vermes I.Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness.J Clin Endocrinol Metab. 2001 Jun;86(6):2811-6.
[22]Bernhagen J, Bacher M, Calandra T, Metz CN, Doty SB, Donnelly T, Bucala R.An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.J Exp Med. 1996 Jan 1;183(1):277-82.
[23]Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, Manogue KR, Cerami A, Bucala R. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature. 1993;365(6448):756-9.
[24]Bernhagen J, Krohn R, Lue H, Gregory JL, Zemecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerie-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C. (2007) MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment, Nat Med. 13:587-596.
[25]Bemhagen J, Krohn R, Lue H, Gregory JL, Zemecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerie-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 2007;13:587-96.
[26]Bemhagen J, Mitchell RA, Calandra T, Voelter W, Cerami A, Bucala R. Purification, bioactivity, and secondary structure analysis of mouse and human macrophage migration inhibitory factor (MIF).Biochemistry. 1994 Nov 29;33(47):14144-55.
[27]Bernstein E, Caudy AA, Hammond SM, and Hannon GJ. 2001. Role for a bidentate ribonuclease in theinitiation step of RNA interference. Nature 409:363-366.
[28]Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, and Malvy C. 2002. Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo. Biochem. Biophys. Res. Commun. 296:1000-1004.
[29]Beswick EJ, Suarez G, Pinchuk IV, Sierra JC, Reyes VE. (2006) Macrophage Migration Inhibitory Factor Binds to CD74 on Gastric Epithelial Cells and Induces Pro-carcinogenic Events during Helicobacter pyloriInfection. Proc Amer Assoc Cancer Res .47, 395-395.
[30]Birmingham A, Anderson EM, Reynolds A, Ilsley-Tyree D, Leake D, Fedorov Y, Baskerville S, Maksimova E., Robinson K, Karpilow J et al. 2006. 3' UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3:199-204.
[31]Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science 1966; 153:80-2.
[32]Bondensgaard K, Petersen M, Singh SK, Rajwanshi VK, Kumar R, Wengel J, and Jacobsen JP. 2000. Structural studies of LNA:RNA duplexes by NMR: Conformations and implications for RNase H activity. Chemistry (Easton) 6: 2687-2695.
[33]Bozza M. et al. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J. Exp. Med. 189, 341-346(1999).
[34]Braasch DA. and Corey DR. 2001. Locked nucleic acid (LNA): Fine-tuning the recognition of DNA and RNA. Chem. Biol. 8:1-7
[35]Braasch DA., Jensen S, Liu Y, Kaur K, Arar K, White MA, and Corey DR. 2003. RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42: 7967-7975.
[36]Breaker RR. and Joyce GF. 1994. A DNA enzyme that cleaves RNA. Chem. Biol. 1:223-229.
[37]Bridge AJ, Pebemard S, Ducraux A, Nicoulaz AL, and Iggo R. 2003. Induction of an interferon response by RNAi vectors in mammalian cells. Nat. Genet. 34:263-264.
[38]Brown FG, Nikolic-Paterson DJ, Chadban SJ, Dowling J, Jose M, Metz CN, Bucala R, Atkins RC. Urine macrophage migration inhibitory factor concentrations as a diagnostic tool in human renal allograft rejection. Transplantation. 2001 Jun 27;71(12):1777-83
[39]Brown FG, Nikolic-Paterson DJ, Hill PA, Isbel NM, Dowling J, Metz CM et al. Urine macrophage migration inhibitory factor reflects the severity of renal injury in human glomerulonephritis. J Am Soc Nephrol 2002; 13 (Suppl 1):S7-13.
[40]Brummelkamp, T.R., Bernards, R., and Agami, R. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550-553.
[41]Bucala R, Donnelly SC. Macrophage migration inhibitory factor a probable link between inflammation and cancer. Immunity 2007;26:281-5.
[42]Bucala R. (1996) MIF re-discovered: pituitary hormone and glucocorticoid-induced regulator of cytokine production. FASEB J. 7,19-24.
[43]Burger-Kentischer A, Goebel H, Seiler R, Fraedrich G, Schaefer HE, Dimmeler S et al. Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis. Circulation 2002; 105: 1561-6.
[44]Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995; 377:68-71.
[45]Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R.MIF as a glucocorticoid-induced modulator of cytokine production.Nature. 1995 Sep 7;377(6544):68-71.
[46]Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R.MIF as a glucocorticoid-induced modulator of cytokine production.Nature. 1995 Sep 7;377(6544):68-71.
[47]Calandra T, Bemhagen J, Mitchell RA, Bucala R.The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.J Exp Med. 1994 Jun 1;179(6):1895-902.
[48]Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hultner L, Heumann D, Mannel D, Bucala R, Glauser MP.Protection from septic shock by neutralization of macrophage migration inhibitory factor.Nat Med. 2000 Feb;6(2):164-70.
[49]Calandra T, Roger T, Macrophage migration inhibitory factor a regulator of innate immunity. Nat Rev Immunol. 3 (2003) 791-800.
[50]Calandra T, Roger T.Macrophage migration inhibitory factor a regulator of innate immunity. Nat Rev Immunol 2003; 3:791-800.
[51]Calandra T, Bernhagen J, Metz CN. (1995) MIF as a glucocorticoid-induced modulator of cytokine production. Nature.. 377, 68 - 71
[52]Castanotto D, Li H, and Rossi JJ. 2002. Functional siRNA expression from transfected PCR products. RNA 8:1454-1460
[53]Chang F, Steelman LS, Shelton JG, Lee JT, Navolanic PM, Blalock WL, Franklin R, McCubrey JA. Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway. Int J Oncol 2003; 22:469-80.
[54]Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410:37-40.
[55]Chang, J.T. 2004. An economic and efficient method of RNAi vector constructions. Anal. Biochem. 334: 199-200.
[56]Chen JZ, Ji CN, Gu SH, Li JX, Zhao EP, Huang Y, Huang L, Ying K, Xie Y, Mao YM.Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis. Int J Biochem Cell Biol. 2004 Aug;36(8):1554-61 Manning, F.C., & Patiemo, S.R. (1996) Apoptosis: inhibitor or instigator of carcinogenesis. Cancer Invest. 14,455-465
[57]Chen Z, Sakuma M, Zago AC, Zhang X, Shi C, Leng L, Mizue Y, Bucala R, Simon D. Evidence for a role of macrophage migration inhibitory factor in vascular disease.Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):709-14.
[58]Chen, L., Willis, S.N., Wei, A., Smith, B.J., Fletcher, J.I., Hinds, M.G., Colman, P.M., Day, C.L., Adams, J.M., Huang, D.C. (2005) Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell .17,393-403
[59]Chesney J, Metz C, Bacher M, Peng T, Meinhardt A, Bucala R. An essential role for macrophage migration inhibitory factor (MIF) in angiogenesis and the growth of a murine lymphoma. Mol Med. 1999 Mar;5(3):181-191
[60]Chi H, Lu B, Takekawa M, Davis RJ, Flavell RA. GADD45beta/GADD45gamma and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNgamma production in T cells. EMBO J 2004; 23:1576-86.
[61]Choi YS, Thomas T, Kotlyar A, Islam MT, and Baker Jr JR. 2005. Synthesis and functional evalution of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting. Chem. Biol. 12: 35-43.
[62]Claassen GF, Hann SR. A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta -induced cell-cycle arrest. Proc Natl Acad Sci U S A 2000; 97:9498-503.
[63]Cory S, Adams JM, (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer. 2: 647-656.
[64]Cunha FQ, Weiser WY, David JR, Moss DW, Moncada S, Liew FY.Recombinant migration inhibitory factorinduces nitric oxide synthase in murine macrophages.J Immunol. 1993 Mar 1;150(5):1908-12.
[65]Czaudema F, Fechtner M, Dames S, Aygun H, Klippel A, Pronk GJ, Giese K, and Kaufmann J. 2003a. Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res. 31: 2705-2716
[66]Czauderna F, Santel A, Hinz M, Fechtner M, Durieux B, Fisch G, Leenders F, Arnold W, Giese K, Klippel A, et al. 2003b. Inducible shRNA expression for application in a prostate cancer mouse model. Nucleic Acids Res. 31:e127
[67]Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y, Wang XF. Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc Natl Acad Sci U S A 1995; 92:5545-9.
[68]David, J.R. (1966) Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoidcell-antigen interaction. Proc Natl Acad Sci USA. 56, 72-77.
[69]de Jong YP, Abadia-Molina AC, Satoskar AR, Clarke K, Rietdijk ST, Faubion WA et al. Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol 2001; 2:1061- 6.
[70]De Smaele E, Zazzeroni F, Papa S, Nguyen DU, Jin R, Jones J, Cong R, Franzoso G. Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling. Nature 2001; 414:308-13.
[71]Del Sal G, Collavin L, Ruaro ME, Edomi P, Saccone S, Valle GD, Schneider C. Structure, function, and chromosome mapping of the growth-suppressing human homologue of the murine gas1 gene. Proc Natl Acad Sci U S A 1994;91:1848-52.
[72]Denkinger CM, Denkinger M, Kort JJ, Metz C, Forsthuber TG . In vivo blockade of macrophage migration inhibitory factor ameliorates acute experimental autoimmune encephalomyelitis by impairing the homing of encephalitogenic T cells to the central nervous system. J Immunol 2003; 170:1274- 82.
[73]Donnelly SC, Haslett C, Reid PT, Grant IS, Wallace WA, Metz CN, Bruce LJ, Bucala R.Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.Nat Med. 1997 Mar;3(3):320-3.
[74]Fingerle-Rowson G, Petrenko O, Metz CN, Forsthuber TG, Mitchell R, Huss R, Moll U, Muller W, Bucala R.The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting.Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9354-9.
[75]Donze O and Picard D. 2002. RNA interference in mammalian cells using siRNAs synthesized with T7 RNA polymerase. Nucleic Acids Res. 30: e46.
[76]Dykxhoorn DM. and Lieberman J. 2006. RUNNING INTERFERENCE: Prospects and obstacles to using small interfering RNAs as small molecule drugs. Annu. Rev. Biomed. Eng. 8:377-402.
[77]Dykxhoorn DM, Novina CD, and Sharp PA. 2003. Killing the messenger: Short RNAs that silence gene expression. Nat. Rev. Mol. Cell Biol. 4: 457-467.
[78]Eisenman RN. Deconstructing myc. Genes Dev 2001; 15(16):2023-30.
[79]Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, and Tuschl T. 2001a. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494-498.
[80]Elbashir SM, Harborth J, Weber K, and Tuschl T. 2002. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26:199-213.
[81]Elbashir, S.M., Lendeckel, W., and Tuschl, T. 2001b. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Dev. 15:188-200.
[82]Elbashir SM., Martinez J, Patkaniowska A, Lendeckel W, and Tuschl T. 2001c. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. 20: 6877-6888.
[83]Elmen J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y, Wahren B, Liang Z, Orum H, Koch T,et al. 2005. Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res. 33:439-447
[84]Evdokiou A, Cowled PA.Tumor-suppressive activity of the growth arrest-specific gene GAS1 in human tumor cell lines. Int J Cancer 1998; 75:568-77.
[85]Farokhzad OC, Jon S, Khademhosseini A, Tran TN, Lavan DA., and Langer R. 2004. Nanoparticle-aptamer bioconjugates: A new approach for targeting prostate cancer cells. Cancer Res. 64:7668-7672.
[86]Feldman AR. and Sen D. 2001. A new and efficient DNA enzyme for the sequence-specific cleavage of RNA. J.Mol.Biol. 313:283-294.
[87]Fingerie-Rowson G, Petrenko O, Metz CN, Forsthuber TG, Mitchell R, Huss R, Moll U, Muller W, Bucala R.2003; The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting. Proc Natl Acad Sci U S A 100:9354-9.
[88]Fire A, Xu S, Montgomery MK., Kostas SA, Driver SE, and Mello CC. 1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-811.
[89]Foote A, Briganti EM, Kipen Y, Santos L, Leech M, Morand EF . Macrophage migration inhibitory factor in systemic lupus erythematosus. J Rheumatol 2004; 31:268- 73.
[90]Frigo DE, Tang Y, Beckman BS, Scandurro AB, Alam J, Burow ME, McLachlan JA. Mechanism of AP-1 -mediated gene expression by select organochlorines through the p38 MAPK pathway. Carcinogenesis 2004; 25:249-61.
[91]Froidevaux C, Roger T, Martin C, Glauser MP, Calandra T. Macrophage migration inhibitory factor and innate immune responses to bacterial infections. Crit Care Med. 2001 Jul;29(7 Suppl):S13-5.
[92]Galaktionov K, Chen X, Beach D. Cdc25 cell-cycle phosphatase as a target of c-myc. Nature 1996;382:511-7.
[93]Gando, S. et al. Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome. Intensive Care Med. 27,1187-1193 (2001).
[94]Gilley J, Coffer PJ, Ham J. (2003) FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons, J Cell Biol. 162:613-622.
[95]Girgenrath M, Weng S, Kostek CA, Browning B, Wang M, Brown SA, Winkles JA, Michaelson JS, Allaire N,
[96]Schneider P, Scott ML, Hsu YM, Yagita H, Flavell RA, Miller JB, Burkly LC, Zheng TS. TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration. EMBO J 2006; 25:5826-39.
[97]Grafia X, Reddy EP. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs),growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995; 11:211-9.
[98]Grimm, D. and Kay, M.A. 2006. Therapeutic short hairpin RNA expression in the liver: Viral targets and vectors. Gene Ther. 13: 563-575
[99]Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, and Kay MA. 2006.
[100]Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441: 537-541.
[101]Gross A, McDonnell JM, & Korsmeyer SJ. (1999) BCL-2 family members and the mitochondria in apoptosis. Gene Dev. 13,1899-1911
[102]Gupta S, Davis RJ. MAP kinase binds to the NH2-terminal activation domain of c-Myc. FEBS Lett 1994; 353:281-5.
[103]Gupta S, Schoer RA, Egan JE, Hannon GJ, and Mittal V. 2004. Inducible, reversible, and stable RNA interference in mammalian cells. Proc. Natl. Acad. Sci. 101:1927-1932.
[104]Hagemann T, Robinson SC, Thompson RG, Charles K, Kulbe H, Balkwill FR.Ovarian cancer cell-derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis.Mol Cancer Ther. 2007 Jul;6(7):1993-2002.
[105]Hall AH, Wan J, Shaughnessy EE, Ramsay Shaw B, and Alexander KA. 2004. RNA interference using boranophosphate siRNAs: Structure-activity relationships. Nucleic Acids Res. 32:5991-6000.
[106]Hallbrink M, Floren A, Elmquist A, Pooga M, Bartfai T, and Langel U. 2001. Cargo delivery kinetics of cell-penetrating peptides. Biochim. Biophys. Acta 1515:101-109.
[107]Han S, Mahato RI, Sung YK, and Kim SW. 2000. Development of biomaterials for gene therapy. Mol. Ther. 2:302-317.
[108]Hannon GJ. 2002. RNA interference. Nature 418: 244-251
[109]Harada N, Nakayama M, Nakano H, Fukuchi Y, Yagita H, Okumura K. Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells. Biochem Biophys Res Commun 2002; 299:488-93.
[110]Harada H, Quearry B, Ruiz-Vela A, & Korsmeyer SJ. (2004) Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity. Proc. Natl. Acad. Sci. USA. 101,15313-15317.
[111]Harbour JW, Dean DC. Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2000; 2:E65-7.
[112]Heath-Engel HM, & Shore GC, (2006) Mitochondrial membrane dynamics, cristae remodeling and apoptosis. Biochim Biophys Acta. 1763, 549-560.
[113]Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, and Bauer S. 2004. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303: 1526-1529
[114]Hilfiker-Kleiner D, Hilfiker A, Castellazzi M, Wollert KC, Trautwein C, Schunkert H, Drexler H. JunD attenuates phenylephrine-mediated cardiomyocyte hypertrophy by negatively regulating AP-1 transcriptional activity. Cardiovasc Res 2006; 71:108-17.
[115]Holen, T, Amarzguioui, M., Wiiger, M.T., Babaie, E., and Prydz, H. 2002. Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor. Nucleic Acids Res. 30:1757-1766.
[116]Hollins AJ, Benboubetra M, Omidi Y, Zinselmeyer BH, Schatzlein AG, Uchegbu IF, and Akhtar S. 2004. Evaluation of generation 2 and 3 poly(propylenimine) dendrimers for the potential cellular delivery of antisense oligonucleotides targeting the epidermal growth factor receptor. Phanm Res. 21:458-466.
[117]Homung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A., et al. 2005. Sequence-specific potent induction of IFN- by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11: 263-270.
[118]Huang B. and Kochanek S. 2005. Adenovirus-mediated silencing of huntingtin expression by shRNA. Hum. Gene Ther. 16: 618-626.
[119]Huang DC. and Strasser A. 2000. BH3-only proteins — essential initiators of apoptotic cell death. Cell 103,839-842.
[120]Hudson JD, Shoaibi MA, Maestro R, Camero A, Hannon GJ, Beach DH. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med. 1999 Nov 15; 190(10): 1375-82
[121]Hughes JA. and Rao GA. 2005. Targeted polymers for gene delivery. Expert Opin. Drug Deliv. 2:145-157. Hurlin PJ, Queva C, Koskinen PJ, Steingrimsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN. Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J 1995; 14:5646-59.
[121]lavarone A, Massague J. Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-beta in cells lacking the CDK inhibitor p15. Nature 1997; 387:417-22.
[122]lnoue H, Hayase Y, Imura A, Iwai S, Miura K, and Ohtsuka E. 1987. Synthesis and hybridization studies on two complementary nona(2'-O-methyl)ribonucleotides. Nucleic Acids Res. 15: 6131-6148.
[123]lshizaka K, Ishii Y, Nakano T. Sugie K. Biochemical basis of antigen-specific suppressor T cell factors: controversies and possible answers. Adv. Immunol. 74,1-60 (2000).
[124]lwabuchi K, Li B, Massa HF, Trask BJ, Date T, Fields S. Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2. J Biol Chem 1998; 273:26061-8.
[125]Jackson, A.L., Burchard, J., Leake, D., Reynolds, A., Schelter, J., Guo, J., Johnson, J.M., Lim, L., Karpilow, J., Nichols, K., et al. 2006. Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12:1197-1205.
[126]Jaworski DC, Jasinskas A, Metz CN, Bucala R, Barbour AG.Identification and characterization of a homologue of the pro-inflammatory cytokine Macrophage Migration Inhibitory Factor in the tick, Amblyomma americanum.Insect Mol Biol. 2001 Aug;10(4):323-31.
[127]Ji, J., Wernli, M., Klimkait, T., and Erb, P. 2003. Enhanced gene silencing by the application of multiple specific small interfering RNAs. FEBS Lett. 552: 247-252.
[128]Jin R, De Smaele E, Zazzeroni F, Nguyen DU, Papa S, Jones J, Cox C, Gelinas C, Franzoso G. Regulation of the gadd45beta promoter by NF-kappaB. DNA Cell Biol 2002; 21:491-503.
[129]Jing A, Chen YM & Huang ZW. (2004) Critical Upstream Signals of Cytochrome c Release Induced by a Novel Bcl-2 Inhibitor J. Biol. Chem., 279(18), 19133-19140
[130]Judge AD, Sood V, Shaw JR, Fang D, McClintock K, and MacLachlan I. 2005. Sequence-dependentstimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol. 23: 457-462
[131]Kaltschmidt B, Kaltschmidt C, Hehner SP, Droge W, Schmitz ML. Repression of NF-kappaB impairs HeLa cell proliferation by functional interference with cell cycle checkpoint regulators. Oncogene 1999; 18:3213-25.
[132]Kamesaki H, Nishizawa K, Michaud GY, Cossman J, Kiyono T. TGF-beta 1 induces the cyclin-dependent kinase inhibitor p27Kip1 mRNA and protein in murine B cells. J Immunol 1998; 160:770-7.
[133]Kang H, Delong R, Fisher MH, and Juliano RL. 2005. Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides. Pharm. Res. 22:2099-2106.
[134]Kariko K, Bhuyan P, Capodici J, and Weissman D. 2004. Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3. J. Immunol. 172: 6545-6549.
[135]Kawakami S, Hattori Y, Lu Y, Higuchi Y, Yamashita F, and Hashida M. 2004. Effect of cationic charge on receptor-mediated transfection using mannosylated cationic liposome/plasmid DNA complexes following the intravenous administration in mice. Pharmazie 59:405-408.
[136]Kawasaki H. and Taira K. 2003. Short hairpin type of dsRNAs that are controlled by tRNAVal promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells. Nucleic Acids Res. 31:700-707
[136]Kawasaki H, Suyama E, lyo M, and Taira K. 2003. siRNAs generated by recombinant human Dicer induce specific and significant but target site-independent gene silencing in human cells. Nucleic Acids Res. 31: 981-987.
[137]Keller M. 2005. Lipidic carriers of RNA/DNA oligonucleotides and polynucleotides: What a difference a formulation makes! J. Control. Release 103: 537-540.
[138]Khvorova A, Reynolds A, and Jayasena SD. 2003. Functional siRNAs and miRNAs exhibit strand bias. Cell 115: 209-216.
[139]Kim DH, Behlke MA., Rose SD, Chang MS, Choi S, and Rossi JJ. 2005a. Synthetic dsRNA Dicersubstrates enhance RNAi potency and efficacy. Nat. Biotechnol. 23:222-226.
[140]Kim DH, Longo M, Han Y, Lundberg P, Cantin E, and Rossi JJ. 2004. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat. Biotechnol. 22: 321-325.
[141]Kim EM, Jeong HJ, Park IK, Cho CS, Moon HB, Yu DY, Bom HS, Sohn MH, and Oh IJ. 2005b. Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): In vitro and in vivo studies. J. Control. Release 108:557-567.
[142]Kireeva ML, Lam SC, Lau LF. Adhesion of human umbilical vein endothelial cells to the immediate-early gene product Cyr61 is mediated through integrin alphavbeta3. J Biol Chem 1998; 273:3090-6.
[143]Kireeva ML, MO FE, Yang GP, Lau LF. Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion. Mol Cell Biol 1996; 16:1326-34.
[144]Kleemann R, Kapumiotu A, Frank RW, Gessner A, Mischke R, Flieger O, Juttner S, Brunner H, Bernhagen J.Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase.J Mol Biol. 1998 Jul 3;280(1):85-102.
[145]Kleemann R, Hausser A, Geiger G, Mischke R, Burger-Kentischer A, Flieger O, Johannes FJ, Roger T, Calandra T, Kapumiotu A, Grell M, Finkelmeier D, Brunner H, Bernhagen J. (2000) Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature. 408,211-216.
[146]Klein E, Ben-Bassat H, Neumann H, Ralph P, Zeuthen J, Polliack A, Vanky F. Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia. Int J Cancer. 1976 Oct 15;18(4):421-31.
[147]Klinge CM, Silver BF, Driscoll MD, Sathya G, Bambara RA, Hilf R. Chicken ovalbumin upstream promoter-transcription factor interacts with estrogen receptor, binds to estrogen response elements and half-sites, and inhibits estrogen-induced gene expression. J Biol Chem 1997; 272:31465-74.
[148]Koli K, Hyytiainen M, Ryynanen MJ, Keski-Oja J. Sequential deposition of latent TGF-beta binding proteins(LTBPs) during formation of the extracellular matrix in human lung fibroblasts. Exp Cell Res 2005; 310:370-82.
[149]Koli K, Wempe F, Stemer-Kock A, Kantola A, Komor M, Hofmann WK, von Melchner H, Keski-Oja J. Disruption of LTBP-4 function reduces TGF-beta activation and enhances BMP-4 signaling in the lung. J Cell Biol 2004; 167:123-33.
[150]Kong YZ, Yu X, Tang JJ, Ouyang X, Huang XR, Fingerle-Rowson G et al. Macrophage migration inhibitory factor induces MMP-9 expression: implications for destabilization of human atherosclerotic plaques. Atherosclerosis 2005; 178: 207- 15.
[151]Korenjak M, Taylor-Harding B, Binne UK, Satterlee JS, Stevaux O, Aasland R, White-Cooper H, Dyson N, Brehm A. Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Cell 2004; 119:181-93.
[152]Kraynack BA. and Baker BF. 2006. Small interfering RNAs containing full 2'-O-methylribonucleotide- modified sense strands display Argonaute2/elF2C2-dependent activity. RNA 12:163-176.
[153]Lan HY, Bacher M, Yang N, Mu W, Nikolic-Paterson DJ, Metz C et al. The pathogenic role of macrophage migration inhibitory factor in immunologically induced kidney disease in the rat. J Exp Med 1997; 185:1455- 65.
[154]Lan HY, Mu W, Yang NS, Meinhardt A, Nikolicpaterson DJ, Ng YY et al. De novo renal expression of macrophage migration inhibitory factor during the development of rat crescentic glomerulonephritis. Am J Pathol 1996:149:1119-27.
[155]Lan HY, Yang N, Metz C, Mu W, Song Q, Nikolic-Paterson DJ, Bacher M, Bucala R, Atkins RC.TNF-alpha up-regulates renal MIF expression in rat crescentic glomerulonephritis.Mol Med. 1997 Feb;3(2): 136-44.
[156]Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA, and Sullenger BA. 2004. In vivo activity of nuclease-resistant siRNAs. RNA 10: 766-771.
[157]Lee YS, Nakahara K, Pham JW. Kim K, He Z, Sontheimer EJ, and Carthew RW. 2004. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117:69-81.
[158]Leech M, Metz C, Bucala R, Morand EF. Regulation of macrophage migration inhibitory factor by endogenous glucocorticoids in rat adjuvant-induced arthritis. Arthritis Rheum. 2000 Apr;43(4):827-33
[159]Leech M, Metz CN, Smith M, Weedon H, Holdsworth SR, Bucala R et al. Macrophage migration inhibitory factor (MIF) in rheumatoid arthritis: evidence for pro-inflammatory function and regulation by glucocorticoids. Arthritis Rheum 1999; 42:1601- 8.
[160]Lehmann LE, Novender U, Schroeder S, Pietsch T, von Spiegel T, Putensen C, Hoeft A, Stuber F. Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis. Intensive Care Med. 2001 Aug;27(8):1412-5.
[161]Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A (2006) A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125: 987-1001.
[162]Lei K, & Davis RJ. (2003) JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc. Natl. Acad. Sci. USA. 100, 2432-2437
[163]Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R. MIF signal transduction initiated by binding to CD74. J Exp Med 2003; 197:1467-76.
[164]Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R. MIF signal transduction initiated by binding to CD74. J Exp Med. 2003 Jun 2;197(11): 1467-76
[165]Lesnik, E.A., Guinosso, C.J., Kawasaki, A.M., Sasmor, H., Zounes, M., Cummins, L.L., Ecker, D.J., Cook, P.D., and Freier, S.M. 1993. Oligodeoxynucieotides containing 2'-O-modified adenosine: Synthesis and effects on stability of DNA.RNA duplexes. Biochemistry 32: 7832-7838.
[166]Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, & Korsmeyer SJ. (2002) Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer herapeutics. Cancer Cell. 2, 183-192,
[167]Leuschner PJ, Ameres SL, Kueng S, and Martinez J. 2006. Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 7: 314-320.
[168]Lewis DL, Hagstrom JE, Loomis AG, Wolff JA, and Herweijer H. 2002. Efficient delivery of siRNA for inhibition of gene expression in postnatal mice. Nat. Genet. 32:107-108.
[169]Li L, Elledge SJ, Peterson CA, Bales ES, Legerski RJ. (1994) Specific association between the human DNA repair proteins XPA and ERCC1. Proc. Natl. Acad. Sci. USA, 91: 5012-5016.
[170]Li MJ, Bauer G, Michienzi A, Yee JK, Lee NS, Kim J, Li S, Castanotto D, Zaia J, and Rossi JJ. 2003. Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs. Mol. Ther. 8:196-206.
[171]Liao H, Bucala R, & Mitchell RA. (2003) Adhesion-dependent Signaling by Macrophage Migration Inhibitory Factor (MIF)* J. Biol. Chem. 278, 76-81
[172]Lin BR, Chang CC, Chen LR, Wu MH, Wang MY, Kuo IH, Chu CY, Chang KJ, Lee PH, Chen WJ, Kuo ML, Lin MT. Cysteine-rich 61 (CCN1) enhances chemotactic migration, transendothelial cell migration, and intravasation by concomitantly up-regulating chemokine receptor 1 and 2. Mol Cancer Res 2007;5:1111-23
[173]Lin MT, Chang CC, Chen ST, Chang HL, Su JL, Chau YP, Kuo ML. Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation. J Biol Chem 2004; 279:24015-23.
[174]Linke SP, Clarkin KC, Di Leonardo A, Tsou A, Wahl GM. A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev 1996; 10:934-47.
[175]LinksKim KS, Seu YB, Baek SH, Kim MJ, Kim KJ, Kim JH, Kim JR. Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism. Mol Biol Cell 2007; 18:4543-52.
[176]Liu JW, Chandra D, Tang SH, Chopra D, Tang DGIdentification and characterization of Bimgamma, anovel proapoptotic BH3-only splice variant of Bim.Cancer Res. 2002 May 15;62(10):2976-81
[177]Liu L, Chen J, Zhang J, Ji C, Zhang X, Gu S, Xie Y, Mao Y. Overexpression of BimSs3, the novel isoform of Bim, can trigger cell apoptosis by inducing cytochrome c release from mitochondria. Acta Biochim Pol. 2007;54(3):603-10.
[178]Liu CM, Liu DP, Dong WJ, and Liang CC. 2004a. Retrovirus vector-mediated stable gene silencing in human cell. Biochem. Biophys. Res. Commun. 313: 716-720.
[179]Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, and Hannon GJ. 2004b. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437-1441.
[180]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25:402-8.
[181]Lue H, Kapumiotu A, Fingerle-Rowson G, Roger T, Leng L, Thiele M, Calandra T, Bucala R, Bernhagen J. Rapid and transient activation of the ERK MAPK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on JAB1/CSN5 and Src kinase activity. Cell Signal 2006; 18:688-703.
[182]Mahat, R.I., Monera, O.D., Smith, L.C., and Rolland, A. 1999. Peptide-based gene delivery. Curr. Opin. Mol. Ther. 1:226-243.
[183]Mahato, R.I., Cheng, K., and Guntaka, R.V. 2005. Modulation of gene expression by antisense and antigene oligodeoxynucleotides and small interfering RNA. Expert Opin. Drug Deliv. 2: 3-28.
[184]Makita, H. et al. Effect of anti-macrophage migration inhibitory factor antibody on lipopolysaccharide-induced pulmonary neutrophil accumulation. Am. J. Respir. Crit. Care Med. 158, 573-579 (1998).
[185]Manoharan M. 2004. RNA interference and chemically modified small interfering RNAs. Curr. Opin. Chem. Biol. 8: 570-579.
[186]Marani M, Tenev T, Hancock D, Downward J, Lemoine NR.Identification of novel isoforms of the BH3domain protein Bim which directly activate Bax to trigger apoptosis.Mol Cell Biol. 2002 Jun;22(11):3577-89.
[187]Marshall, W.S. and Kaiser, R.J. 2004. Recent advances in the high-speed solid phase synthesis of RNA. Curr. Opin. Chem. Biol. 8: 222-229.
[188]Marson AL, Tarr DE, Scott AL. Macrophage migration inhibitory factor (mif) transcription is significantly elevated in Caenorhabditis elegans dauer larvae. Gene. 2001 Oct 31;278(1-2):53-62.
[189]Massague J. G1 cell-cycle control and cancer. Nature 2004; 432:298-306.
[190]Matranga C, Tomari Y, Shin C, Bartel DP, and Zamore PD. 2005. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123: 607-620.
[191]Matsukura, S., Jones, PA, and Takai, D. 2003. Establishment of conditional vectors for hairpin siRNA knockdowns. Nucleic Acids Res. 31: e77.
[192]McCaffrey, A.P., Meuse, L., Pham, T.T., Conklin, D.S., Hannon, G.J., and Kay, M.A. 2002. RNA interference in adult mice. Nature 418:38-39.
[193]McNamara II, J.O., Andrechek, E.R., Wang, Y., Viles, K.D., Rempel, R.E., Gilboa, E., Sullenger, B.A., and Giangrande, P.H. 2006. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat. Biotechnol. 24: 1005-1015
[193]Meister, G. and Tuschl, T. 2004. Mechanisms of gene silencing by double-stranded RNA. Nature 431: 343-349
[194]Meister, G., Landthaler, M., Patkaniowska, A., Dorsett, Y., Teng, G., and Tuschl, T. 2004. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol. Cell 15:185-197.
[195]Menendez JA, Vellon L, Mehmi I, Teng PK, Griggs DW, Lupu R. A novel CYR61-triggered 'CYR61-alphavbeta3 integrin loop' regulates breast cancer cell survival and chemosensitivity through activation of ERK1/ERK2 MAPK signaling pathway. Oncogene 2005; 24:761-79.
[196]Merdan, T., Callahan, J., Petersen, H., Kunath, K., Bakowsky, U., Kopeckova, P., Kissel, T., and Kopecek, J. 2003. Pegylated polyethylenimine-Fab' antibody fragment conjugates for targeted gene delivery to humanovarian carcinoma cells. Bioconjug. Chem. 14:989-996.
[197]Meyer-Siegler KL, Leifheit EC, Vera PL. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells. BMC Cancer 2004;4:34.
[198]Milligan JF. and Uhlenbeck OC. 1989. Synthesis of small RNAs using T7 RNA polymerase. Methods Enzymol. 180: 51-62.
[199]Mitchell RA, Liao H, Chesney J, Fingerie-Rowson G, Baugh J, David J, Bucala R. Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response. Proc Natl Acad Sci U S A 2002; 99:345-350.
[200]Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase (MAPK) andcytoplasmic phospholipase A2 activation by macrophage migration inhibitory factor (MIF). Regulatory role in cell proliferation and glucocorticoid action. J Biol Chem. 1999 Jun 18;274(25): 18100-6.
[201]Mitchell RA. Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal 2004; 16:13-9.
[202]Mitchell RA, Liao H, Chesney J, Fingerie-Rowson G, Baugh J, David J, Bucala R. (2002) Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response.Proc Natl Acad Sci U S A. 99(1),345-350.
[203]Mittelstadt PR, Ashwell JD. Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ. J Biol Chem 2001;276:29603-10.
[204]Mizue Y, Nishihira J, Miyazaki T, Fujiwara S, Chida M, Nakamura K et al. Quantitation of macrophage migration inhibitory factor (MIF) using the one-step sandwich enzyme immunosorbent assay: elevated serum MIF concentrations in patients with autoimmune diseases and identification of MIF in erythrocytes. Int J Mol Med 2000; 5: 397-403.
[205]Morand EF, Leech M, Weedon H, Metz C, Bucala R, Smith MD. Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations. Rheumatology (Oxford) 2002; 41:558- 62.
[206]Morand EF. New therapeutic target in inflammatory disease: macrophage migration inhibitory factor. Intern Med J 2005; 35:419-26.
[207]Moreau C, Cartron PF, Hunt A, Mefiah K, Green DR, Evan G, Vallette FM, Juin P. (2003)Minimal BH3 peptides promote cell death by antagonizing anti-apoptotic proteins. J Biol Chem. 278,19426-19435
[208]Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, Dickinson B, McSwiggen JA, Vargeese C,Bowman K, Shaffer CS, et al. 2005a. Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41:1349-1356.
[209]Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, Hartsough K, Machemer L, Radka S., Jadhav V., et al. 2005b. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23:1002-1007.
[210]Mosmann T 1983 Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55-63
[211]Mufioz NM, Upton M, Rojas A, Washington MK, Lin L, Chytil A, Sozmen EG, Madison BB, Pozzi A, Moon RT, Moses HL, Grady WM. Transforming growth factor beta receptor type II Inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation. Cancer Res. 2006; 66:9837-44.
[212]Murakami H, Akbar SM, Matsui H, Onji M . Macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis: clinical implications and pathogenic significance. Eur J Clin Invest 2001; 31: 337-43.
[213]Myers JW, Jones JT, Meyer T, and Ferrell Jr JE. 2003. Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing. Nat. Biotechnol. 21:324-328.
[214]Naito Y, Yamada T, Ui-Tei K, Morishita S, and Saigo K. 2004. siDirect Highly effective, target-specific siRNA design software for mammalian RNA interference. Nucleic Acids Res. 32: W124-W129.
[215]Nemajerova A, Moll UM, Petrenko O, Fingerle-Rowson G. Macrophage migration inhibitory factor coordinates DNA damage response with the proteasomal control of the cell cycle. Cell Cycle 2007; 6:1030-4.
[216]Nguyen MT, Lue H, Kleemann R, Thiele M, Tolle G, Finkelmeier D, Wagner E, Braun A, Bemhagen J. The cytokine macrophage migration inhibitory factor reduces pro-oxidative stress-induced apoptosis. J Immunol 2003:170:3337-47.
[217]Niino M, Ogata A, Kikuchi S, Tashiro K, Nishihira J . Macrophage migration inhibitory factor in thecerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Behcet's disease. J Neurol Sci 2000; 179:127- 31.
[218]Nishihira J, Ishibashi T, Fukushima T, Sun B, Sato Y, Todo S. Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis. Ann N Y Acad Sci. 2003 May;995:171-82.Nishihira, J.(2000) Macrophage migration inhibitory factor (MIF): Its essential role in the immune system and cell growth. J Interferon Cytokine Res. 20,751-762
[219]Nishitani H, Taraviras S, Lygerou Z, Nishimoto T. The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase. J Biol Chem 2001; 276:44905-11.
[219]Nishitsuji H, Kohara M, Kannagi M, and Masuda T. 2006. Effective suppression of humanimmunodeficiency virus type 1 through a combination of short- or long-hairpin RNAs targeting essential sequences for retroviral integration. J. Virol. 80: 7658-7666.
[220]No D, Yao TP, and Evans RM. 1996. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc. Natl. Acad. Sci. 93: 3346-3351.
[221]Norris JL, Baldwin AS Jr. Oncogenic Ras enhances NF-kappaB transcriptional activity through Raf-dependent and Raf-independent mitogen-activated protein kinase signaling pathways. J Biol Chem 1999; 274:13841-6.
[222]Nykanen, A., Haley, B., and Zamore, P.D. 2001. ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107: 309-321.
[223]Obaya AJ, Mateyak MK, Sedivy JM.Mysterious liaisons: the relationship between c-Myc and the cell cycle. Oncogene 1999; 18:2934-41.
[224]O'Connor, L., Strasser, A., O'Reilly, L.A., Hausmann, G., Adams, J.M., Cory, S., Huang, D.C.(1998) Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 17(2), 384-395.
[225]Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG. Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. J Biol Chem 1996; 271:30322-5.
[226]Ohkawa J. and Taira K. 2000. Control of the functional activity of an antisense RNA by a tetracycline-responsive derivative of the human U6 snRNA promoter. Hum. Gene Ther. 11:577-585.
[227]Ohkawara T, Nishihira J, Takeda H, Hige S, Kato M, Sugiyama T et al. Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice. Gastroenterology 2002; 123:256-70.
[228]Onodera S, Kaneda K, Mizue Y, Koyama Y, Fujinaga M, Nishihira J . Macrophage migration inhibitory factor up-regulates expression of matrix metalloproteinases in synovial fibroblasts of rheumatoid arthritis. J Biol Chem 2000; 275: 444- 50.
[229]Onodera S, Nishihira J, Iwabuchi K, Koyama Y, Yoshida K, Tanaka S, Minami A. Macrophage migration inhibitory factor up-regulates matrix metalloproteinase-9 and -13 in rat osteoblasts. Relevance to intracellular signaling pathways. J Biol Chem. 2002 Mar 8;277(10):7865-74.
[230]Onodera S, Nishihira J, Koyama Y, Majima T, Aoki Y, Ichiyama H et al. Macrophage migration inhibitory factor up-regulates the expression of interleukin-8 messenger RNA in synovial fibroblasts of rheumatoid arthritis patients: common transcriptional regulatory mechanism between interleukin-8 and interleukin-1 beta. Arthritis Rheum 2004; 50:1437-47.
[231]Onodera S, Suzuki K, Matsuno T, Kaneda K, Takagi M, Nishihira J. Macrophage migration inhibitory factor induces phagocytosis of foreign particles by macrophages in autocrine and paracrine fashion. Immunology 1997; 92:131-7.
[232]Onodera S, Tanji H, Suzuki K, Kaneda K, Mizue Y, Sagawa A, Nishihira J.High expression of macrophage migration inhibitory factor in the synovial tissues of rheumatoid joints.Cytokine. 1999 Feb;11(2): 163-7.
[233]Osterhout JL, Waheed AA, Hiol A, Ward RJ, Davey PC, Nini L, Wang J, Milligan G, Jones TL, Druey KM. Palmitoylation regulates regulator of G-protein signaling (RGS) 16 function. II. Palmitoylation of a cysteine residue in the RGS box is critical for RGS16 GTPase accelerating activity and regulation of Gi-coupled signalling. J Biol Chem 2003; 278:19309-16.
[234]Paddison, P.J., Caudy, A.A., Bernstein, E., Hannon, G.J., and Conklin, D.S. 2002. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes & Dev. 16: 948-958.
[235]Pan JH, Sukhova GK, Yang JT, Wang B, Xie T, Fu H et al. Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 2004; 109: 3149-53.
[236]Paul CP, Good PD, Winer I, and Engelke DR. 2002. Effective expression of small interfering RNA in human cells. Nat. Biotechnol. 20: 505-508.
[237]Pelengaris S, Khan M, Evan G. C-MYC: more than just a matter of life and death. Nat Rev Cancer 2002; 2:764-76.
[238]Perez-Roger I, Kim SH, Griffiths B, Sewing A, Land H. Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1). EMBO J 1999 Oct 1;18(19):5310-20.
[239]Persengiev SP, Zhu X, and Green MR. 2004. Nonspecific, concentration-dependent stimulation andrepression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 10:12-18.
[240]Petrenko O, Moll UM. Macrophage migration inhibitory factor MIF interferes with the Rb-E2F pathway. Mol Cell 2005; 17(2):225-36.
[241]Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S, Yaniv M. Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell 1994; 76:747-60.
[242]Piva R, Belardo G, Santoro MG. NF-kappaB: a stress-regulated switch for cell survival. Antioxid Redox Signal 2006; 8:478-86.
[243]Potten CS, Booth D, Haley JD. Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo. Br J Cancer 1997; 75:1454-9.
[244]Prall OW, Sarcevic B, Musgrove EA, Watts CK, Sutherland RL. Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J Biol Chem 1997; 272:10882-94.
[245]Pulverer BJ, Hughes K, Franklin CC, Kraft AS, Leevers SJ, Woodgett JR. Co-purification of mitogen-activated protein kinases with phorbol ester-induced c-Jun kinase activity in U937 leukaemic cells. Oncogene 1993; 8:407-15.
[246]Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR. Phosphorylation of c-jun mediated by MAP kinases. Nature 1991; 353:670-4.
[247]Putcha GV, Harris CA, Moulder KL, Easton RM, Thompson CB, Johnson EM Jr. (2002) Intrinsic and Extrinsic Pathway Signaling during Neuronal Apoptosis: Lessons from the Analysis of Mutant Mice. J Cell Biol. 157(3), 441-53
[248]Puthalakath H, Huang DC, O'Reilly LA, King SM, & Strasser A. (1999) The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell 3,287-296
[249]Rathmell JC, & Thompson CB.(2002) Pathways of Apoptosis in Lymphocyte Development, Homeostasis, and Disease. Cell. 109,97-107
[250]Ravitz MJ, Wenner CE. Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-beta. Adv Cancer Res 1997; 71:165-207.
[251]Ren Y, Chan HM, Fan J, Xie Y, Chen YX, Li W, Jiang GP, Liu Q, Meinhardt A, Tam PK. Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma. Oncogene. 2006 Jun 15;25(25):3501-8.
[252]Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, Wong J.Macrophage migration inhibitory factorstimulates angiogenic factor expression and correlates with differentiation and lymph node status in patients with esophageal squamous cell carcinoma. Ann Surg. 2005 Jul;242(1):55-63.
[253]Ren Y, Tsui HT, Poon RT, Ng IO, Li Z, Chen Y, Jiang G, Lau C, Yu WC, Bacher M, Fan ST. Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma. Int J Cancer. 2003 Oct 20;107(1 ):22-9.
[254]Reynisdottir I, Polyak K, lavarone A, Massague J. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev 1995; 9:1831-45.
[255]Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, and Khvorova A. 2004. Rational siRNA design for RNA interference. Nat. Biotechnol. 22:326-330.
[256]Roger T, David J, Glauser MP, Calandra T.MIF regulates innate immune responses through modulation of Toll-like receptor 4.Nature. 2001 Dec 20-27;414(6866):920-4
[257]Roger T, Froidevaux C, Martin C, Calandra T.Macrophage migration inhibitory factor (MIF) regulates host responses to endotoxin through modulation of Toll-like receptor 4 (TLR4).J Endotoxin Res. 2003;9(2):119-23.
[258]Rosengren E, Aman P, Thelin S, Hansson C, Ahlfors S, Bjork P, Jacobsson L, Rorsman H. The macrophage migration inhibitory factor MIF is a phenylpyruvate tautomerase.FEBS Lett. 1997 Nov 3;417(1):85-8.
[259]Rosengren E, Bucala R, Aman P, Jacobsson L, Odh G, Metz CN, Rorsman H. The immunoregulatory mediator macrophage migration inhibitory factor (MIF) catalyzes a tautomerization reaction.Mol Med. 1996 Jan;2(1):143-9.
[260]Ruan W, Xu E, Xu F, Ma Y, Deng H, Huang Q, Lv B, Hu H, Lin J, Cui J, Di M, Dong J, Lai M. IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis. Cancer Biol Ther 2007; 6:354-9.
[261)Ruaro EM, Collavin L, Del Sal G, Haffner R, Oren M, Levine AJ, Schneider C. A proline-rich motif in p53 is required for transactivation-independent growth arrest as induced by Gas1. Proc Natl Acad Sci U S A 1997; 94:4675-80.
[262]Rubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J, Rooney DL, Ihrig MM, McManus MT, Gertler FB, et al. 2003. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat. Genet. 33:401-406.
[263]Saharinen J, Taipale J, Monni O, Keski-Oja J. Identification and characterization of a new latent transforming growth factor-beta-binding protein, LTBP-4. J Biol Chem 1998; 273:18459-69.
[264]Sampey AV, Hall PH, Mitchell RA, Metz CN, Morand EF . Regulation of synoviocyte phospholipase A2 and cyclooxygenase 2 by macrophage migration inhibitory factor. Arthritis Rheum 2001; 44:1273- 80.
[265]Santhakumaran LM, Thomas T, and Thomas TJ. 2004. Enhanced cellular uptake of a triplex-forming oligonucleotide by nanoparticle formation in the presence of polypropylenimine dendrimers. Nucleic Acids Res. 32:2102-2112.
[266]Santos L, Lacey DC, Yang Y, Leech M, Morand EF . Activation of synovial cell p38 MAP kinase by macrophage migration inhibitory factor (MIF). J Rheumatol 2004; 31:1038- 43.
[267]Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS,Minn AJ. et al. (1997). Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.Science 275,983 -986.
[268]Schepers U. 2005. RNA interference in practice: Principles, basics, and methods for gene silencing in C. elegans, Drosophila, and mammals , Wiley-VCH, New York.
[269]Schmidt M, Fernandez de Mattos S, van der Horst A, Klompmaker R, Kops GJ, Lam EW, Burgering BM, Medema RH. Cell cycle inhibition by FoxO forkhead transcription factors involves downregulation of cyclin D.Mol Cell Biol 2002; 22:7842-52.
[270]Schober A, Bernhagen J, Thiele M, Zeiffer U, Knarren S, Roller M et al. Stabilization of atherosclerotic plaques by blockade of macrophage migration inhibitory factor after vascular injury in apolipoprotein E-deficient mice. Circulation 2004; 109: 380- 85.
[271]Schomber T, Kalberer CP, Wodnar-Filipowicz A, and Skoda RC. 2004. Gene silencing by lentivirus- mediated delivery of siRNA in human CD34+ cells. Blood 103:4511-4513.
[272]Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, and Zamore PD. 2003. Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199-208.
[273]Scott DK, Mitchell JA, Granner DK. The orphan receptor COUP-TF binds to a third glucocorticoid accessory factor element within the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem 1996;271:31909-14.
[274]Semizarov D, Frost L, Sarthy A, Kroeger P, Halbert DN, and Fesik SW. 2003. Specificity of short interfering RNA determined through gene expression signatures. Proc. Natl. Acad. Sci. 100:6347-6352.
[275]Shand JH, Beattie J, Song H, Phillips K, Kelly SM, Flint DJ, Allan GJ. Specific amino acid substitutionsdetermine the differential contribution of the N- and C-terminal domains of insulin-like growth factor (IGF)-binding protein-5 in binding IGF-I. J Biol Chem 2003; 278:17859-66.
[276]Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002; 4:E131-6.
[277]Shimizu T, Nishihira J, Mizue Y, Nakamura H, Abe R, Watanabe H et al. High macrophage migration inhibitory factor (MIF) serum levels associated with extended psoriasis. J Invest Dermatol 2001; 116:989- 90..
[278]Siolas D, Lemer C, Burchard J, Ge W, Linsley PS, Paddison PJ, Hannon GJ, and Cleary MA. 2005. Synthetic shRNAs as potent RNAi triggers. Nat. Biotechnol. 23:227-231.
[279]Sioud M. 2004. Therapeutic siRNAs. Trends Pharmacol. Sci. 25:22-28.
[280]Sioud M. 2005. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J. Mol. Biol. 348: 1079-1090.
[281]Sioud M. 2006. Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: A central role for 2'-hydroxyl uridines in immune responses. Eur. J. Immunol. 36: 1222-1230.
[282]Sohail M, Doran G, Riedemann J, Macaulay V, and Southern EM. 2003. A simple and cost-effective method for producing small interfering RNAs with high efficacy. Nucleic Acids Res. 31: e38.
[283]Song E, Lee SK, Dykxhoorn DM, Novina C, Zhang D, Crawford K, Cerny J, Sharp PA, Lieberman J, Manjunath N, Shankar P. 2003a. Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages. J. Virol. 77: 7174-7181.
[284]Song E, Lee SK, Wang J, Ince N, Ouyang N, Min J, Chen J, Shankar P, Lieberman J. 2003b. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat. Med. 9:347-351.
[285]Song E, Zhu P, Lee SK, Chowdhury D, Kussman S, Dykxhoom DM, Feng Y, Palliser D, Weiner DB, Shankar P, Marasco WA, Lieberman J. 2005. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat. Biotechnol. 23: 709-717.
[286]Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Moroy T, Bartek J, Massague J, Hanel F,
[287]Eilers M. Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol 2001; 3:392-9.
[288]Steinhoff M, Meinhardt A, Steinhoff A, Gemsa D, Bucala R, Bacher M . Evidence for a role of macrophage migration inhibitory factor in psoriatic skin disease. Br J Dermatol 1999; 141:1061-6.
[289]Su B, Karin M. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr Opin Immunol 1996; 8:402-11.
[290]Subramanya HS, Roper DI, Dauter D, Dodson EJ, Davies GJ, Wilson KS and Wigley DB (1996) Enzymaticketonization of 2-hydroxymuconate: specificity and mechanism investigated by the crystal structures of two isomerases. Biochemistry, 35,792-802
[291]Sugimoto H, Taniguchi M, Nakagawa A, Tanaka I, Suzuki M, Nishihira J.Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1.54 A resolution.Biochemistry. 1999 Mar 16;38(11):3268-79
[292]Sun B, Nishihira J, Yoshiki T, Kondo M, Sato Y, Sasaki F, Todo S. Macrophage migration inhibitory factor promotes tumor invasion and metastasis via the Rho-dependent pathway. Clin Cancer Res. 2005 Feb 1;11(3):1050-8.
[293]Sun HW, Bernhagen J, Bucala R, Lolis E.Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor.Proc Natl Acad Sci U S A. 1996 May 28;93(11):5191-6.
[294]Sun L, Chen C. Expression of transforming growth factor beta type III receptor suppresses tumorigenicity of human breast cancer MDA-MB-231 cells. J Biol Chem 1997; 272:25367-72.
[295]Sun B, Nishihira J, Suzuki M, Fukushima N, Ishibashi T, Kondo M, Sato Y, Todo S. (2003) Induction of macrophage migration inhibitory factor by lysophosphatidic acid: relevance to tumor growth and angiogenesis..Int J Mol Med. 12(4), 633-641.
[296] Suzuki M, Sugimoto H, Nakagawa A, Tanaka I, Nishihira J, Sakai M.Crystal structure of the macrophage migration inhibitory factor from rat liver.Nat Struct Biol. 1996 Mar;3(3):259-66.
[297]Swant JD, Rendon BE, Symons M, Mitchell RA. (2005) Rho GTPase-dependent Signaling Is Required for Macrophage Migration Inhibitory Factor-mediated Expression of Cyclin D1. J. Biol. Chem. 280,23066-23072
[298]Swant JD, Rendon BE, Symons M, Mitchell RA. Rho GTPase-dependent signaling is required for macrophage migration inhibitory factor-mediated expression of cyclin D1. J Biol Chem 2005; 280:23066-72.
[299]Swope MD, Lolis E. Macrophage migration inhibitory factor cytokine, hormone, or enzyme? Rev Physiol Biochem Pharmacol. 1999;139:1-32.
[300TTakekawa M, Saito H. A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell 1998; 95:521-30.
[301]Talos F, Mena P, Fingerle-Rowson G, Moll U, Petrenko O.MIF loss impairs Myc-induced lymphomagenesis. Cell Death Differ. 2005 Oct;12(10):1319-28
[302]Taniguchi Y, Yorioka N, Yamashita K, Masaki T, Yamakido M . Macrophage migration inhibitory factor in IgA nephropathy. Kidney Int 1998; 54:2245- 6.
[303]Tiscomia G, Singer O, Ikawa M, and Verma IM. 2003. A general method for gene knockdown in mice by using lentiviral vectors expressing small interfering RNA. Proc. Natl. Acad. Sci. 100:1844-1848.
[304]Toh ML, Aeberll D, Lacey D, Yang Y, Santos LL, Clarkson M, Sharma L, Clyne C, Morand EF. Regulation of IL-1 and TNF receptor expression and function by endogenous macrophage migration inhibitory factor. J Immunol. 2006 Oct 1;177(7):4818-25.
[305]Truhlar SM, Torpey JW, Komives EA. Regions of IkappaBalpha that are critical for its inhibition of NF-kappaB.DNA interaction fold upon binding to NF-kappaB. Proc Natl Acad Sci U S A 2006; 103:18951-6.
[306]Tsuneoka M, Teye K, Arima N, Soejima M, Otera H, Ohashi K, Koga Y, Fujita H, Shirouzu K, Kimura H,Koda Y. A novel Myc-target gene, mimitin, that is involved in cell proliferation of esophageal squamous cell carcinoma. J Biol Chem 2005; 280:19977-85.
[307]U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001 Nov 30;509(1):135-41
[308]Ui-Tei, K., Naito, Y., Takahashi, F., Haraguchi, T., Ohki-Hamazaki, H., Juni, A., Ueda, R., and Saigo, K. 2004. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res. 32: 936-948.
[309]Van Craenenbroeck, K., Vanhoenacker, P., Leysen, J.E., and Haegeman, G. 2001. Evaluation of the tetracycline- and ecdysone-inducible systems for expression of neurotransmitter receptors in mammalian cells. Eur. J. Neurosci. 14: 968-976.
[310]Van Der Heide LP, Hoekman MF, Smidt MP. The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation. Biochem J 2004; 380:297-309.
[311]Van Kuilenburg AB, Van Beeumen JJ, Demol H, Van den Bogert C, Schouten I, Muijsers AO. Subunit IV of human cytochrome c oxidase, polymorphism and a putative isoform. Biochim Biophys Acta. 1992 Feb 26;1119(2):218-24.
[312]Van Waes C. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res 2007; 13:1076-82.
[313]Vlach J, Hennecke S, Alevizopoulos K, Conti D, Amati B. Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c-Myc. EMBO J 1996 Dec 2;15(23):6595-604.
[314]Weiser WY, Temple PA, Witek-Giannotti JS, Remold HG, Clark SC, David JR. Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor.Proc Natl Acad Sci U S A. 1989 Oct;86(19):7522-6.
[315]Welford SM, Bedogni B, Gradin K, Poellinger L, Broome Powell M, Giaccia AJ. HIF1alpha delays premature senescence through the activation of MIF. Genes Dev 2006;20:3366-71.
[316]Welford SM, Bedogni B, Gradin K, Poellinger L, Powell MB, & Giaccia AJ. (2006) HIF1 delays premature senescence through the activation of MIF.Gene Dev.20,3366-3371
[317]White ES,Flaherty KR,Carskadon S,Brant A,lannettoni MD,Yee J,Orringer MB,Arenberg DA.Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer,role in angiogenesis and prognosis.Clin Cancer Res.2003 Feb;9(2):853-60
[318]Whitmarsh A J,Davis RJ.Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways.J Mol Med 1996;74:589-607.
[319]Wilson JM,Coletta PL,Cuthbert R J,Scott N,MacLennan K,Hawcroft G,Leng L,Lubetsky JB,Jin KK,Lolis E,Medina F,Brieva JA,Poulsom R,Markham AF,Bucala R,Hull MA.Macrophage migration inhibitory factor promotes intestinal tumorigenesis.Gastroenterology.2005 Nov;129(5):1485-503
[320]Wiznerowicz M.and Trono D.2003.Conditional suppression of cellular genes:Lentivirus vector-mediated drug-inducible RNA interference.J.Virol.77:8957-8961.
[321]Wohlschlegel JA,Dwyer BT,Dhar SK,Cvetic C,Walter JC,Dutta A.Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.Science 2000;290:2309-12.
[322]Wong LF,Ralph GS,Walmsley LE,Bienemann AS,Parham S,Kingsman SM,Uney JB,Mazarakis ND.2005.Lentiviral-mediated delivery of Bcl-2 or GDNF protects against excitotoxicity in the rat hippocampus.Mol.Ther.11:89-95.
[323]Wooddell Cl,Van Hout CV,Reppen T,Lewis DL,and Herweijer H.2005.Long-term RNA interference from optimized siRNA expression constructs in adult mice.Biochem.Biophys.Res.Commun.334:117-127.
[324]Wu X,Li Y,Crise B,and Burgess SM.2003.Transcription start regions in the human genome are favored targets for MLV integration.Science 300:1749-1751
[325]Xia H,Mao Q,Paulson HL,and Davidson BL.2002.siRNA-mediated gene silencing in vitro and in vivo.Nat.Biotechnol.20:1006-1010.
[326]Xie D,Yin D,Tong X,O'Kelly J,Mori A,Miller C,Black K,Gui D,Said JW,Koeffler HP.Cyr61 is overexpressed in gliomas and involved in integrin-linked kinase-mediated Akt and beta-catenin-TCF/Lef signaling pathways.Cancer Res 2004;64:1987-96.
[327]Yang BS,Hauser CA,Henkel G,Colman MS,Van Beveren C,Stacey KJ,Hume DA,Maki RA,Ostrowski MC.Ras-medlated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2.Mol Cell Biol 1996;16:538-47.
[328]Yang D,Buchholz F,Huang Z,Goga A,Chen CY,Brodsky FM,Bishop JM.2002.Shod RNA duplexes produced by hydrolysla with Eschedchia coli RNase Ⅲ mediate effective RNA interference in mammalian cells. Proc. Natl. Acad. Sci. 99: 9942-9947.
[329]Ye Z, Cheng K, Guntaka RV, and Mahato RI. 2005. Targeted delivery of a triplex-forming oligonucleotide to hepatic stellate cells. Biochemistry 44:4466-4476
[330]Yoshida Y, Tanaka S, Umemori H, Minowa O, Usui M, Ikematsu N, Hosoda E, Imamura T, Kuno J, Yamashita T, Miyazono K, Noda M, Noda T, Yamamoto T. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell 2000; 103:1085-97.
[331]Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 2000; 92:1472-89.
[332]Yuan B, Latek R, Hossbach M, Tuschl T, and Lewitter F. 2004. siRNA Selection Server: An automated siRNA oligonucleotide prediction server. Nucleic Acids Res. 32: W130-W134.
[333]Yudin AI, Goldberg E, Robertson KR, Overstreet JW. Calpain and calpastatin are located between the plasma membrane and outer acrosomal membrane of cynomolgus macaque spermatozoa. J Androl. 2000 Sep-Oct;21(5):721-9
[334]Zamore, P.D. and Haley, B. 2005. Ribo-gnome: The big world of small RNAs. Science 309:1519-1524.
[335]Zhang Y, Neo SY, Han J, Yaw LP, Lin SC. RGS16 attenuates galphaq-dependent p38 mitogen-activated protein kinase activation by platelet-activating factor. J Biol Chem 1999; 274:2851-7.
[336]Zhang, C., Tang, N., Liu, X., Liang, W., Xu, W., and Torchilin, V.P. 2006. siRNA-containing liposomes modified with polyarginine effectively silence the targeted gene. J. Control. Release 112:229-239