紫外线诱导的Axin介导的细胞死亡需要PML的参与
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
体轴发育抑制因子Axin是一种多功能构架蛋白,在多条信号传导途径中发挥重要作用:在Wnt信号通路中,Axin作为负调控因子,下调β-catenin的水平;在JNK信号通路中,Axin与MEKK1或MEKK4相互结合,激活JNK,诱导细胞凋亡;在TGF-β信号通路中,Axin通过磷酸化Smad3增强转录活性;在p53信号通路中,Axin与p53,HIPK2形成三聚体复合物,调节p53的转录活性。这些信号途径对细胞的各种生理过程如细胞的生长,增殖,分化,癌变,凋亡及细胞周期起着重要的调控作用。
     PML是一个很重要的抑癌因子,最初是从急性早幼粒白血病(acute promyelocytic leukemia,APL)病人的细胞中,鉴定并克隆出来。细胞中,PML主要分布在nuclear body上。PML-NB的成分错综复杂,包含SUMO-1, Sp100, Sp140, CBP, BLM, Daxx, pRB, p53等多种重要的信号分子,可见PML-NB参与多条信号转导途径。在APL中,PML与RARα基因融合,融合蛋白与野生型的PML发生异源二聚化,引起PML的异常分布,破坏NB,导致肿瘤抑制,细胞增殖、分化、存活的紊乱。
     众所周知,Axin和PML都是抑癌因子,都参与p53诱导的凋亡,但两者之间的直接联系还不清楚。因此,本论文采用生物化学,分子生物学和细胞生物学的方法对Axin和PML之间的关系进行研究和阐述,初步揭示了PML在Axin诱导细胞死亡中的作用。本论文发现:( 1 ) UV刺激可促使Axin从细胞浆转移到细胞核,并定位于PML-NB。( 2 ) Axin可与PML相互作用。( 3 ) Axin诱导的p53的活化需要PML的参与,PML的显性负作用突变体及其siRNA都可强烈抑制Axin激活p53。( 4 ) PML和Axin均参与UV诱导的细胞死亡。( 5 ) Axin诱导的细胞死亡需要PML的参与,PML的显性负作用突变体及其siRNA可以抑制Axin引起的细胞死亡。
     综上所述,本论文发现,PML在UV引起的Axin介导的细胞死亡中发挥重要作用,对我们今后进一步认识Axin作为多功能构架蛋白,在多信号通路中的作用及生物学效应具有重要意义。
Axin (Axis inhibitor) is a scaffold protein which plays important roles in multiple signal-transduction pathways. In the Wnt signaling pathway, Axin stimulates degradation ofβ-catenin by forming a large multimeric protein complex with APC, GSK-3βandβ-catenin. In JNK signaling, Axin activates JNK by directly binding to MEKK1 or MEKK4. In TGF-βsignaling, Axin enhances the transcriptional activity of Smad3. Besides, Axin regulates the transcriptional activity of p53 by forming a protein complex with p53 and HIPK2. These different signaling pathways control cellular processes, including cell proliferation, differentiation, transformation, apoptosis and cell cycle arrest.
     PML, an important tumor suppressor, was originally cloned and identified from APL patient. It locates on the PML-NB, which is a multimetric complex containing SUMO-1, Sp100, Sp140, CBP, BLM, Daxx, pRB, p53 and so on. In APL patients, PML fuses with RARα, and the resulting fusion protein dimerizes with PML and interfere with the formation of nuclear body, leading to the disorder of survival, proliferation, differentiation of normal cell and tumor suppression.
     It has been shown that both Axin and PML are tumor suppressors and are involved in p53-induced apoptosis, but the relationship between them is not clear. In this study, taking advantage of the methods of biochemistry, molecular biology and cell biology, I focused on the relationship between Axin and PML, and discovered that PML plays an important role in Axin induced cell death. (1) UV irradiation stimulates redistribution of Axin from cytoplasm to PML-NB in the nucleus; (2) Axin interacts with PML; (3) PML is required for Axin-mediated p53 activation, and this activation can be blocked by its dominate forms and siRNA; (4) Both PML and Axin are involved in UV-induced cell death; (5) PML is required for Axin-induced cell death, both dominant negative forms and siRNA of PML can block the process.
     In conclusion, all data give evidence of the effect of PML on UV-induced, Axin-mediated cell death, as sheds a new light on our understanding of Axin.
引文
[1] Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation [J]. Cell,1997, 90: 181-192.
    [2] Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3β and β-catenin and promotes GSK-3β-dependent phosphorylation of β-catenin [J]. EMBO J, 1998, 17: 1371-1384.
    [3] Hedgepeth CM, Deardorff MA, Klein PS. Xenopus axin interacts with glycogen synthase kinase-3β and is expressed in the anterior midbrain [J]. Mech Dev, 1999, 80: 147-151.
    [4] Hamada F, Tomoyasu Y, Takatsu Y, Nakamura M, Nagai S, Suzuki A, Fujita F, Shibuya H, Toyoshima K, Ueno N, Akiyama T. Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin [J]. Science, 1999, 283: 1739-1742.
    [5] Kikuchi. A Roles of Axin in the Wnt signalling pathway [J]. Cell Signal, 1999, 11: 777-788.
    [6] Kikuchi. A Modulation of Wnt signaling by Axin and Axil [J]. Cytokine Growth Factor Rev, 1999, 10: 255-265.
    [7] Salashor S, Woodgett JR. The links between axin and carcinogenesis [J]. J Clin Pathol, 2005, 58: 225-236.
    [8] Druey KM, Blumer KJ, Kang VH, Kehrl JH. Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family [J]. Nature, 1996, 379: 742-746.
    [9] Burchett SA. Regulators of G protein signaling: a bestiary of modular protein binding domains [J]. J Neurochem, 2000, 75: 1335-1351.
    [10] Sussman DJ, Klingensmith J, Salinas P, Adams PS, Nusse R, Perrimon N. Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene disheveled [J]. Dev Biol, 1994, 166: 73-86.
    [11] Behrens J, Jerchow BA, Wurele M, Grimm J, Asbrand C, Wirtz R, Kuhl M, Wedlich D, Birchmeier W. Functional interaction of an axin homolog, conductin, with β-catenin, APC, and GSK3β [?J]. Science, 1998, 280: 596-599.
    [12] Yamamoto H, Kishida S, Uochi T, Ikeda S, Koyama S, Asashima M, Kikuchi A. Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta andbeta-catenin and inhibits axis formation of Xenopus embryos [J]. Mol Cell Biol, 1998, 18: 2867-2875.
    [13] Mai M, Qian C, Yokomizo A, Smith DI and Liu W. Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24 [J]. Genomics, 1999,55: 341-344.
    [14] Dong X, Seelan RS, Qian C, Mai M, Liu W. Genomic structure, chromosome mapping and expression analysis of the human AXIN2 gene [J]. Cytogenet Cell Genet, 2001; 93: 26-28.
    [15] Gumbiner BM, McCrea PD. Catenins as mediators of the cytoplasmic functions of cadherins[J]. J Cell Sci Suppl, 1993, 17: 155-158.
    [16] Peifer M, Orsulic S, Pai LM, Loureiro J. A model system for cell adhesion and signal transduction in Drosophila[J]. Dev Suppl, 1993, 163-176.
    [17] Schneider S, Herrenknecht K, Butz S, Kemler R, Hausen P. Catenins in Xenopus embryogenesis and their relation to the cadherin-mediated cell-cell adhesion system[J]. Development, 1993, 118: 629-640.
    [18] Wodarz A, Nusse R. Mechanisms of Wnt signaling in development[J]. Annu Rev Cell Dev Biol, 1998, 14: 59-88.
    [19] akanaka C, Weiss JB, Williams LT. Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription[J]. Proc Natl Acad Sci U S A, 1998, 95: 3020-3023.
    [20] Hamada F, Tomoyasu Y, Takatsu Y, Nakamura M, Nagai S, Suzuki A, Fujita F, Shibuya H, Toyoshima K, Ueno N, Akiyama T. Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin[J]. Science, 1999, 283: 1739-1742.
    [21] Willert K, Shibamoto S, Nusse R. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex[J]. Genes Dev, 1999, 13: 1768-1773.
    [22] Willert K, Logan CY, Arora A, Fish M, Nusse R. A Drosophila Axin homolog, Daxin, inhibits Wnt signaling[J]. Development, 1999, 126: 4165-4173.
    [23] Korswagen HC, Coudreuse DY, Betist MC, van de Water S, Zivkovic D, Clevers HC. The Axin-like Protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans[J]. Genes Dev, 2002, 16: 1291-1302.
    [24] Fagotto F, Jho E, Zeng L, Kurth T, Joos T, Kaufmann C, Costantini F. Domains of axininvolved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization[J]. J Cell Biol, 1999, 145: 741-756.
    [25] Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis-a look outside the nucleus[J]. Science, 2000, 287: 1606-1609.
    [26] Gao ZH, Seeling JM, Hill V, Yochum A, Virshup DM. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex[J]. Proc Natl Acad Sci U S A, 2002, 99: 1182-1187.
    [27] Hino S, Michiue T, Asashima M, Kikuchi A. Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin[J]. J Biol Chem, 2003, 278: 14066-14073.
    [28] Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta[J]. Curr Biol, 1998, 8: 573-581.
    [29] Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH. Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex[J]. EMBO J, 2003, 22: 494-501.
    [30] Sakanaka C, Williams LT. Functional domains of axin-importance of the C terminus as an oligomerization domain[J]. J Biol Chem, 1999, 274: 14090-14093.
    [31] Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3β and β-catenin and promotes GSK-3β-dependent phosphorylation of β-catenin [J]. EMBO J, 1998, 17: 1371-1384.
    [32] Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism [J]. Cell, 2002, 108: 837-847.
    [33] Aberle HA, Bauer A, Stappert J, Kispert A, Kemler R. β-catenin is a target for the ubiquitin-proteasome pathway [J]. EMBO J, 1997, 16: 3797-3804.
    [34] Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D. A β-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus [J]. Genes Dev, 1997, 11: 2359-2370.
    [35] Laurent MN, Biltz IL, Hashimoto C, Rothbacher U, Cho KW. The Xenopus homeobox genetwin mediates Wnt induction of goosecoid in establishment of Spemann′s organizer [J]. Development, 1997, 124: 4905-4916.
    [36] Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destree O, Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos [J]. Cell, 1996, 86: 391-399.
    [37] Mckendry R, Hsu SC, Harland RM, Grosschedl R. LEF-1/TCF proteins mediate Wnt-inducible transcription from the Xenopus nodal-related 3 promoter [J]. Dev Biol, 1997, 192; 420-431.
    [38] Tetsu O, McCormick F. Β-catenin regulates expression of cyclin D1 in colon carcinoma cells [J]. Nature, 1999, 398; 422-426.
    [39] He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-MYC as a target of the APC pathway [J]. Science, 1998, 281: 1509-1512.
    [40] Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH. Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex [J]. EMBO J, 2003, 22: 494-501.
    [41] Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR. Glycogen synthase kinase-3: functions in oncogenesis and development [J]. Biochim Biophys Acta, 1992, 1114: 147-162.
    [42] Mandelkow EM, Drewes G, Biernat J, Gustke N, Van Lint J, Vandenheede JR, Mandelkow E. Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau [J]. FEBS Lett, 1992, 314; 315-321.
    [43] Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. Binding of GSK-3β to the APC-β-catenin complex andregulation of complex assembly [J]. Science, 1996, 272: 1023-1026.
    [44] Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism [J]. Cell, 2002, 108: 837-847.
    [45] Lee E, Salic A, Kruger R, Heinrich R, Kirschner MW. The Roles of APC and Axin Derived from Experimental and Theoretical Analysis of the Wnt Pathway [J]. Plos Biol, 2003, 1: 116-132.
    [46] Kishida S, Yamamoto H, Ikeda S, Kishida M, Sakamoto I, Koyama S, Kikuchi A. Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin [J]. J Biol Chem, 1998, 273: 10823-10826.
    [47] Hinoi T, Yamamoto H, Kishida M, Takada S, Kishida S, Kikuchi A. Complex formation of adenomatous polyposis coli gene product and axin facilitates glycogen synthase kinase-3 beta-dependent phosphorylation of beta-catenin and down-regulates beta-catenin [J]. J Biol Chem, 2000, 275: 34399-34406.
    [48] Kawahara K, Morishita T, Nakamura T, Hamada F, Toyoshima K, Akiyama T. Down-regulation of beta-catenin by the colorectal tumor suppressor APC requires association with Axin and β-catenin [J]. J Biol Chem, 2000, 275: 8369-8374.
    [49] Rubinfeld B, Albert I, Porfiri E, Munemitsu S, Polakis P. Loss of beta-catenin regulation by the APC tumor suppressor protein correlates with loss of structure due to common somatic mutations of the gene [J]. Cancer Res, 1997, 57: 4624-4630.
    [50] Seeling JM, Miller JR, Gil R, Moon RT, White R, Virshup DM. Regulation of β-Catenin Signaling by the B56 Subunit of Protein Phosphatase 2A [J]. Science, 1999, 283: 2089-2091.
    [51] Peters JM, McKay RM, McKay JP, Graff JM. Casein kinase I transduces Wnt signals [J]. Nature, 1999, 401: 345-350.
    [52] Sakanaka C, Leong P, Xu L, Harrison SD, Williams LT. Casein kinase Iepsilon in the Wnt pathway: regulation of β-catenin function [J]. Proc Natl Acad Sci U S A, 1999, 96: 12548-12552.
    [53] Gao ZH, Seeling JM, Hill V, Yochum A, Virshup DM. Casein kinase I phosphorylates and destabilizes the β-catenin degradation complex [J]. Proc Natl Acad Sci U S A, 2002, 99; 1182-1187.
    [54] Ratcliffe MJ, Itoh K, Sokol SY. A Positive Role for the PP2A Catalytic Subunit in Wnt Signal Transduction [J]. J Biol Chem, 2000, 275: 35680-35683.
    [55] Yamamoto H, Hinoi T, Michiue T, Fukui A, Usui H, Janssens V, Van Hoof C, Goris J, Asashima M, Kikuchi A. Inhibition of the Wnt Signaling Pathway by the PR61 Subunit of Protein Phosphatase 2A [J]. J Biol Chem, 2001, 276: 26875-26882.
    [56] Li X, Yost HJ, Virshup DM, Seeling JM. Protein phosphatase 2A and its B56 regulatorysubunit inhibit Wnt signaling in Xenopus [J]. EMBO J, 2001, 20: 4122-4131.
    [57] Hino S, Michiue T, Asashima M, Kikuchi A. Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin [J]. J Biol Chem, 2003, 278: 14066-14073.
    [58] Wehrli M, Dougan ST, Caldwell K, O′Keefe L, Schwartz S, Vaizel D. Arrow encodes an LDL-receptor-related protein essential for Wingless signaling [J]. Nature, 2000, 407: 527-530.
    [59] Mao J, Wang J, Liu B, Pan W, Farr GH 3rd, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway [J]. Mol Cell, 2001, 7: 801-809.
    [60] Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X. LDL-receptor-related proteins in Wnt signal transduction [J]. Nature, 2000, 407: 530-535.
    [61] Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6 [J]. Curr Biol, 2001, 11: 951-961.
    [62] Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, He X. A mechanism for Wnt coreceptor activation [J]. Mol Cell, 2004, 13: 149-156.
    [63] Gluecksohn-Schoenheimer S. The effects of a lethal mutation responsible for duplications and twinning in mouse embryos [J]. J Exp Zool, 1949, 110: 47-76.
    [64] Jacobs-Cohen RJ, Spiegelman M, Cookingham JC, Bennett D. Knobbly, a new dominant mutation in the mouse that affects embryonic ectoderm organization [J]. Genet Res, 1984, 43: 43-50
    [65] Capelluto DG, Kutateladze TG, Habas R, Finkielstein CV, He X, Overduin M. The DIX domain targets dishevelled to actin stress fibres and vesicular membranes [J]. Nature, 2002, 419: 726-729.
    [66] Ciani L, Krylova O, Smalley MJ, Dale TC, and Salinas PC. A divergent canonical Wnt-signaling pathway regulates microtubule dynamic: disheveled signals locally to stabilize microtubules [J]. J Cell Biol, 2003, 164: 243-253.
    [67] Goold RG, Owen R, and Gordon-Weeks PR. Glycogen synthase kinase 3β phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones [J]. J Cell Sci, 1999, 112: 3373-3384.subunit inhibit Wnt signaling in Xenopus [J]. EMBO J, 2001, 20: 4122-4131.
    [57] Hino S, Michiue T, Asashima M, Kikuchi A. Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin [J]. J Biol Chem, 2003, 278: 14066-14073.
    [58] Wehrli M, Dougan ST, Caldwell K, O′Keefe L, Schwartz S, Vaizel D. Arrow encodes an LDL-receptor-related protein essential for Wingless signaling [J]. Nature, 2000, 407: 527-530.
    [59] Mao J, Wang J, Liu B, Pan W, Farr GH 3rd, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway [J]. Mol Cell, 2001, 7: 801-809.
    [60] Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X. LDL-receptor-related proteins in Wnt signal transduction [J]. Nature, 2000, 407: 530-535.
    [61] Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6 [J]. Curr Biol, 2001, 11: 951-961.
    [62] Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, He X. A mechanism for Wnt coreceptor activation [J]. Mol Cell, 2004, 13: 149-156.
    [63] Gluecksohn-Schoenheimer S. The effects of a lethal mutation responsible for duplications and twinning in mouse embryos [J]. J Exp Zool, 1949, 110: 47-76.
    [64] Jacobs-Cohen RJ, Spiegelman M, Cookingham JC, Bennett D. Knobbly, a new dominant mutation in the mouse that affects embryonic ectoderm organization [J]. Genet Res, 1984, 43: 43-50
    [65] Capelluto DG, Kutateladze TG, Habas R, Finkielstein CV, He X, Overduin M. The DIX domain targets dishevelled to actin stress fibres and vesicular membranes [J]. Nature, 2002, 419: 726-729.
    [66] Ciani L, Krylova O, Smalley MJ, Dale TC, and Salinas PC. A divergent canonical Wnt-signaling pathway regulates microtubule dynamic: disheveled signals locally to stabilize microtubules [J]. J Cell Biol, 2003, 164: 243-253.
    [67] Goold RG, Owen R, and Gordon-Weeks PR. Glycogen synthase kinase 3β phosphorylation of microtubule-associated protein 1B regulates the stability of microtubules in growth cones [J]. J Cell Sci, 1999, 112: 3373-3384.
    [79] Kuan CY, Yang DD, Roy DR, Davis RJ, Rakic P, Flavell RA. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development [J]. Neuron, 1999, 22: 667-676.
    [80] Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains [J]. Science, 1988, 241: 42-52.
    [81] Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner EF. Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2 [J]. Mech Dev, 1999, 89: 115-124.
    [82] Wada T, Nakagawa K, Watanabe T, Nishitai G, Seo J, Kishimoto H, Kitagawa D, Sasaki T, Penninger JM, Nishina H, Katada T. Impaired synergistic activation of stress activated protein kinase SAPK/JNK in mouse embryonic stem cells lacking SEK1/MKK4 [J]. J Biol Chem, 2001, 276: 30892-30897.
    [83] Deng T, Karin M. c-Fos transcriptional activity stimulated by H-Ras-activated protein kinase distinct from JNK and ERK [J]. Nature, 1994, 371: 171-175.
    [84] Gupta S, Campbell D, Derijard B, Davis RJ. Transcription factor ATF2 regulation by the JNK signal transduction pathway [J]. Science, 1995, 267: 389-393.
    [85] Atfi A, Buisine M, Mazars A, Gespach C. Induction of apoptosis by DPC4, a transcriptional factor regulated by transforming growth factor-beta through stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling pathway [J]. J Biol Chem, 1997, 272: 24731-24734.
    [86] Chow CW, Rincon M, Cavanagh J, Dickens M, Davis RJ. Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway [J]. Science, 1997, 278: 1638-1641.
    [87] Smith JL, Schaffiner AE, Hofmeister JK, Hartman M, Wei G, Forsthoefel D, Hume DA, Ostrowski MC. ets-2 is a target for an akt (Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice [J]. Mol Cell Biol, 2000, 20: 8026-8034.
    [88] Huang C, Jacobson K, Schaller MD. A role for JNK-paxillin signaling in cell migration [J]. Cell Cycle, 2004, 3: 4-6.
    [89] Ivanov VN, Krasilnikov M, Ronai Z. Regulation of Fas expression by STAT3 and c-Jun is mediated by phosphatidylinositol 3-kinase-AKT signaling [J]. J Biol Chem, 2000, 277: 4932-4944.
    [90] Milne DM, Campbell LE, Campbell DG, Meek DW. p53 is phosphorylated in vitro and in vivo by an ultraviolet radiation-induced protein kinase characteristic of the c-Jun kinase, JNK1 [J]. J Biol Chem, 1995, 270: 5511-5518.
    [91] Yu K, Ravera CP, Chen YN, McMahon G. Regulation of Myc-dependent apoptosis by p53, c-Jun N-terminal kinases/stress-activated protein kinases, and Mdm-2 [J]. Cell Growth Differ, 1997, 8: 731-742.
    [92] Hu MC, Qiu WR, Wang YP. JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases [J]. Oncogene, 1997, 15: 2277-2287.
    [93] Lee CM, Onesime C, Reddy CD, Dhanasekaran N, Reddy EP. JLP: A scaffolding protein that tethers JNK/p38 MAPK signaling modules and transcription factors [J]. Proc Natl Acad Sci U S A, 2002, 99: 14189-14194.
    [94] Dorow DS, Devereux L, Dietzsch E, Kretser de T. Purfication of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domain [J]. Eur J Biochem, 1993, 213: 701-710.
    [95] Tibbles LA, Ing YL, Kiefer F, Iscove N, Woodgett JR, Lassam N. MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3 [J]. EMBO J, 1996, 15: 7026–7035.
    [96] Tanaka S, Hanafusa H. Guanine-nucleotide exchange protein C3G activates JNK1 by a Ras-independent mechanism. JNK1 activation inhibited by kinase negative forms of MLK3 and DLK mixed lineage kinases [J]. J. Biol. Chem, 1998, 273: 1281-1284.
    [97] Salmeron A, Ahmad TB, Carlile GW, Pappin D, Narsimhan RP, Ley SC. Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase [J]. EMBO J, 1996, 15: 817-826.
    [98] Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K, Gotoh Y. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways [J]. Science, 1997, 275: 90-94.
    [99] Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, Irie K, Nishida E, Matsumoto K. TAB1: an activator of the TAK1 MAPKKK in TGF-β signal transduction [J].Science, 1996, 272: 1179-1182.
    [100] Su B, Jacinto E, Hibi M, Kallunki T, Karin M, Ben-Neriah Y. JNK is involved in signal integration during costimulation of T lymphocytes [J]. Cell, 1994, 77: 727-736.
    [101] DeSilva DR, Feeser WS, Tancula EJ, Scherle PA. Anergic T cells are defective in both jun NH2-terminal kinase and mitogen-activated protein kinase signaling pathways [J]. J Exp Med, 1996, 183: 2017-2023.
    [102] Wilson DJ, Fortner KA, Lynch DH, Mattingly RR, Macara IG, Posada JA, Budd RC. JNK, but not MAPK, activation is associated with Fas-mediated apoptosis in human T cells [J]. Eur J Immunol, 1996, 26: 989-994.
    [103] Yang X, Khosravi-Far R, Chang HY, Baltimore D. Daxx, a novel Fas-binding protein that activates JNK and apoptosis [J]. Cell, 1997, 89: 1067-1076.
    [104] Chang HY, Nishitoh H, Yang X, Ichijo H, Baltimore D. Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx [J]. Science, 1998, 281: 1860-1863.
    [105] Villunger A, Huang DC, Holler N, Tschopp J, Strasser A. Fas ligand-induced c-Jun kinase activation in lymphoid cells requires extensive receptor aggregation but is independent of DAXX, and Fas-mediated cell death does not involve DAXX, RIP, or RAIDD [J]. J Immunol, 2000, 165: 1337-1343.
    [106] Khelifi AF, D'Alcontres MS, Salomoni P. Daxx is required for stress-induced cell death and JNK activation [J].Cell Death Differ, 2005, 12: 724-733.
    [107] Hibi M, Lin A, Smeal T, Minden A, Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain [J]. Genes Dev, 1993, 7: 2135-2148.
    [108] Kennedy NJ, Davis RJ. Role of JNK in tumor development [J]. Cell Cycle, 2003, 2: 199-201.
    [109] Aguirre Ghiso JA, Alonso DF, Farias EF, Gomez DE, de Kier Joffe EB. Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype [J]. Eur J Biochem, 1999, 263: 295-304.
    [110] Davis RJ. Transcriptional regulation by MAP kinases [J]. Mol Reprod Dev, 1995, 42: 459-467.
    [111] Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A. DIX domains of Dvl and Axin are necessary for protein interactions and their ability to regulate beta-catenin stability [J]. Mol Cell Biol, 1999, 19: 4414-4422.
    [112] Zhang Y, Neo SY, Han J, Lin SC. Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase [J]. J Biol Chem, 2000; 275: 25008-25014.
    [113] Luo W, Zou H, Jin L, Lin S, Li Q, Ye Z, Rui H, Lin SC. Axin contains three separable domains that confer intramolecular, homodimeric, and heterodimeric interactions involved in distinct functions [J]. J Biol Chem, 2005, 280: 5054-5060.
    [114] Luo W, Ng WW, Jin LH, Ye Z, Han J, Lin SC. MEKK1 and MEKK4 bind to two distinct regions of Axin, and both require an additional common domain for JNK activation [J]. J Biol Chem, 2003, 278: 37451-37458.
    [115] Zhang Y, Neo SY, Wang X, Han J, Lin SC. Axin forms a complex with MEKK1 and activates c-Jun NH(2)-terminal kinase/stress-activated protein kinase through domains distinct from Wnt signaling [J]. J Biol Chem, 1999, 274: 35247-35254.
    [116] Rui HL, Fan E, Zhou HM, Xu Z, Zhang Y, Lin SC. SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling [J]. J Biol Chem, 2002, 277: 42981-42986.
    [117] Massague J. TGF-beta signal transduction [J]. Annu Rev Biochem, 1998, 67: 753-791.
    [118] Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins [J]. Nature, 1997, 390: 465-471.
    [119] Chakrabarty S, Fan D, Varani J. Modulation of differentiation and proliferation in human colon carcinoma cells by transforming growth factor beta 1 and beta 2 [J]. Int J Cancer, 1990, 46: 493-499.
    [120] Jass JR, Do KA, Simms LA, Iino H, Wynter C, Pillay SP, Searle J, Radford-Smith G, Young J, Leggett B. Morphology of sporadic colorectal cancer with DNA replication errors [J]. Gut, 1998, 42: 673-679.
    [121] Furuhashi M, Yagi K, Yamamoto H, Furukawa Y, Shimada S, Nakamura Y, Kikuchi A, Miyazono K, Kato M. Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway [J]. Mol Cell Biol, 2001, 21: 5132-5141.
    [122] Melnick A, Licht JD. Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia [J]. Blood, 1999, 93: 3167-3215.
    [123] Le XF, Yang P, Chang KS. Analysis of the growth and transformation suppressor domains of promyelocytic leukemia gene, PML [J]. J. Biol. Chem, 1996, 271:130-135.
    [124] Hodges M, Tissot C, Howe K, Grimwade D, Freemont PS. Structure, organization, and dynamics of promyelocytic leukaemia protein nuclear bodies [J]. Am. J. Hum. Genet, 1998, 63: 297-304.
    [125] LaMorte VJ, Dyck JA, Ochs RL, Evans RM. Localization of nascent RNA and CREB binding protein with the PML-containing nuclear body [J]. Proc. Natl Acad. Sci. USA, 1998, 95: 4991-4996.
    [126] Alcalay M, Tomassoni L, Colombo E, Stoldt S, Grignani F, Fagioli M, Szekely L, Helin K, Pelicci PG. The promyelocytic leukaemia gene product (PML) forms stable complexes with the retinoblastoma protein [J]. Mol Cell Biol, 1998, 18: 1084-1093.
    [127] Zhong S, Hu P, Ye TZ, Stan R, Ellis NA, Pandolfi PP. A role for PML and the nuclear body in genomic stability [J]. Oncogene, 1999, 18: 7941-7947.
    [128] Zhong S, Salomoni P, Ronchetti S, Guo A, Ruggero D, Pandolfi PP. PML and Daxx participate in a novel nuclear pathway for apoptosis [J]. J Exp Med, 2000, 191: 631-640. [129 Zhang Y, Xiong Y. Mutations in human ARF exon 2 disrupt its nucleolar localization and impairs its ability to block nuclear export of MDM 2 and p53 [J]. Mol Cell, 1999, 3: 579-591.
    [130] Chan JY, Li L, Fan YH, Mu ZM, Zhang WW, Chang KS. Cell-cycle regulation of DNA damage-induced expression of the suppressor gene PML [J]. Biochem Biophys Res Commun, 1997, 240: 640-646.
    [131] Stuurman N, de Graaf A, Floore A, Josso A, Humbel B, de Jong L, van Driel R. A monoclonal antibody recognizing nuclear matrixassociated nuclear bodies [J]. J Cell Sci, 1992, 101: 773-784.
    [132] Cohen N, Sharma M, Kentsis A, Perez JM, Strudwick S, Borden KL. PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA [J]. EMBO J, 2001, 20: 4547-4559.
    [133] Maul GG, Yu E, Ishov AM, Epstein AL. Nuclear domain 10 (ND10) associated proteins arealso present in nuclear bodies and redistribute to hundreds of nuclear sites after stress [J]. J Cell Biochem,1995, 59: 498-513.
    [134] Lavau C, Marchio A, Fagioli M, Jansen J, Falini B, Lebon P, Grosveld F, Pandolfi PP, Pelicci PG, Dejean A. The acute promyelocytic leukaemia-associated PML gene is induced by interferon [J]. Oncogene, 1995, 11: 871-876.
    [135] Borden KL, Campbell Dwyer EJ, Salvato MS. Salvato. An arenavirus RING (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the cytoplasm [J]. J Virol, 1998, 72: 758-766.
    [136] Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF 3rd, Maul GG. PML is critical for ND10 formation and recruits the PML-interacting protein Daxx to this nuclear structure when modified by SUMO-1[J]. J Cell Biol, 1999, 147: 221-234.
    [137] Boddy MN, Howe K, Etkin LD, Solomon E, Freemont PS. PIC1, a novel ubiquitin-like protein which interacts with the PML component of a multiprotein complex that is disrupted in acute promyelocytic leukaemia [J]. Oncogene, 1996, 13: 971-982.
    [138] Muller S, Matunis MJ, Dejean A. Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus [J]. EMBO J, 1998, 17: 61-70.
    [139] Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET. Identification of three major sentrinization sites in PML [J]. J Biol Chem, 1998, 273: 26675-26682.
    [140] Sternsdorf T, Jensen K, Will H. Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1 [J]. J Cell Biol, 1997, 139: 1621-1634.
    [141] Sternsdorf T, Jensen K, Reich B, Will H. The nuclear dot protein Sp100, characterization of domains necessary for dimerization, subcellular localization, and modification by small ubiquitinlike modifiers [J]. J Biol Chem, 1999, 274: 12555-12566.
    [142] Zhong S, Muller S, Freemont PS, Dejean A, Pandolfi PP. Role of SUMO-1 modified PML in nuclear body formation [J]. Blood, 2000, 95: 2748-2752.
    [143] Li SJ, Hochstrasser M. A new protease required for cell-cycle progression in yeast [J]. Nature, 1999, 398: 246-251.
    [144] Gong L, Millas S, Maul GG, Yeh ET. Differential regulation of sentrinized proteins by anovel sentrin-specific protease [J]. J Biol Chem, 2000, 275: 3355-3359.
    [145] Perez A, Kastner P, Sethi S, Lutz Y, Reibel C, Chambon P. PML/RAR homodimers: distinct DNA binding properties and heteromeric interactions with RAR [J]. EMBO J, 1993, 12: 3171-3182.
    [146] Vogelstein B, Lane D, Levine AJ. Surfing the p53 network [J]. Nature, 2000, 408: 307-310.
    [147] Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2 [J]. Nature, 1997, 387: 299-303.
    [148] Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53 [J]. Nature, 1997, 387: 296-299.
    [149] Caelles C, Helmberg A, Karin M. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes [J]. Nature, 1994, 370: 220-223.
    [150] Haupt Y, Rowan S, Shaulian E, Vousden KH and Oren M. Induction of apoptosis in HeLa cells by trans-activation-deficient p53 [J]. Genes Dev, 1995, 9: 2170-2183.
    [151] Marchenko ND, Zaika A, Moll UM. Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling [J]. J Biol Chem, 2000, 275: 16202-16212.
    [152] Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM. p53 has a direct apoptogenic role at the mitochondria [J]. Mol Cell, 2003, 11: 577-590.
    [153] Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP. The function of PML in p53-dependent apoptosis [J]. Nat Cell Biol, 2000, 2: 730-736.
    [154] Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, chneider C, Del Sal G. Regulation of p53 activity in nuclear bodies by a specific PML isoform [J]. EMBO J, 2000, 19: 6185-6195.
    [155] Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP and Pelicci PG. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature. 2000 Jul 13;406(6792):207-210.
    [156] Kim YH, Choi CY, Lee SJ, Conti MA and Kim Y. Homeodomain interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors [J]. J Biol Chem, 1998, 273: 25875-25879.
    [157] Hofmann TG, Mincheva A, Lichter P, Droge W and Lienhard Schmitz M. Humanhomeodomain-interacting protein kinase-2 (HIPK2) is a member of the DYRK family of protein kinases and maps to chromosome 7q32–q34 [J]. Biochimie, 2000, 82: 1123-1127.
    [158] Choi CY, Kim YH, Kwon HJ, Kim Y. The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription [J]. J Biol Chem, 1999, 274: 33194-33197.
    [159] Pierantoni GM, Fedele M, Pentimalli F, Benvenuto G, Pero R, Viglietto G, Santoro M, Chiariotti L, Fusco A. High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth [J]. Oncogene, 2001, 20: 6132-6341.
    [160] D’Orazi G, Cecchinelli B, Bruno T, Manni I, Higashimoto Y, Saito S, Gostissa M, Coen S, Marchetti A, Del Sal G, Piaggio G, Fanciulli M, Appella E and Soddu S. Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis [J]. Nat Cell Biol, 2002, 4: 11-19.
    [161] Hofmann TG, Moller A, Sirma H, Zentgraf H, Taya Y, Droge W, Will H, Schmitz ML. Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol, 2002, 4: 1-10.
    [162] Li X, Wang Y, Debatin KM, Hug H. The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells [J]. Biochem Biophys Res Commun, 2000, 277: 513-517.
    [163] Rochat-Steiner V, Becker K, Micheau O, Schneider P, Burns K, Tschopp J. FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits fas-mediated Jun NH(2)-terminal kinase activation [J]. J Exp Med, 2000, 192: 1165-1174.
    [164] Yang X, Khosravi-Far R, Chang HY, Baltimore D. Daxx, a novel Fas-binding protein that activates JNK and apoptosis [J]. Cell, 1997, 89: 1067-1076.
    [165] Chang HY, Nishitoh H, Yang X, Ichijo H and Baltimore D. Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx [J]. Science, 1998, 281: 1860-1863.
    [166] Gongora R, Stephan RP, Zhang Z, Cooper MD. An essential role for Daxx in the inhibition of B lymphopoiesis by type I interferons [J]. Immunity, 2001, 14: 727-737.
    [167] Raoul C, Estevez AG, Nishimune H, Cleveland DW, deLapeyriere O, Henderson CE, bHaase G, Pettmann B. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations [J]. Neuron, 2002, 35: 1067-1083.
    [168]Torii S, Egan DA, Evans RA, Reed JC. Human Daxx regulates Fasinduced apoptosis from nuclear PML oncogenic domains (PODs) [J]. EMBO J, 1999, 18: 6037-6049.
    [169] Li R, Pei H, Watson DK, Papas TS. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes [J]. Oncogene, 2000, 19: 745-753.
    [170] Lehembre F, Muller S, Pandolfi PP, Dejean A. Regulation of Pax3 transcriptional activity by SUMO-1-modified PML [J]. Oncogene, 2001, 20: 1-9.
    [171] Emelyanov AV, Kovac CR, Sepulveda MA, Birshtein BK. The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells [J]. J Biol Chem, 2002, 277: 11156-11164.
    [172] Ko YG, Kang YS, Park H, Seol W, Kim J, Kim T, Park HS, Choi EJ, Kim S. Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm [J]. J Biol Chem, 2001, 276: 39103-39106.
    [173] Charette SJ, Lambert H, Landry J. A kinase-independent function of Ask1 in caspase-independent cell death [J]. J Biol Chem, 2001, 276: 36071-36074.
    [174] Perlman R, Schiemann WP, Brooks MW, Lodish HF, Weinberg RA. TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation [J]. Nat Cell Biol, 2001, 3: 708-714.
    [175] Zhong S, Salomoni P, Pandolfi PP. The transcriptional role of PML and the nuclear body. Nat Cell Biol,. 2000, 2: E85-90.
    [176] Li H, Leo C, Zhu J, Wu X, O’Neil J, Park EJ, Chen JD. Sequestration and inhibition of Daxx-mediated transcriptional repression by PML [J]. Mol Cell Biol, 2000, 20:1784-1796.
    [177] Ecsedy JA, Michaelson JS, Leder P. Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity [J]. Mol Cell Biol, 2003, 23: 950-960.
    [178] Hofmann TG, Stollberg N, SchmitzML, Will H. HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells [J]. Cancer Res, 2003, 63: 8271-8277.
    [179] Stadler M, Chelbi-Alix MK, Koken MH, Venturini L, Lee C, Saib A, Quignon F, Pelicano L,Guillemin MC, Schindler C, et al. Transcriptional induction of the PML growth suppressor gene by interferons is mediated through an ISRE and GAS element [J]. Oncogene, 1995, 11: 2565-2573.
    [180] Guldner HH, Szostecki C, Grotzinger T, Will H. IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis [J]. J Immunol, 1992, 149, 4067-4073.
    [181] Gongora C, David G, Pintard L, Tissot C, Hua TD, Dejean A, Mechti N. Molecular cloning of a new interferon-induced PML nuclear body-associated protein [J]. J Biol Chem, 1997, 272: 19457-19463
    [182] Terris B, Baldin V, Dubois S, Degott C, Flejou JF, Henin D, Dejean A. PML nuclear bodies are general targets for inflammation and cell proliferation [J]. Can Res, 1995, 55: 1590-1597.
    [183] Zheng P, Guo Y, Niu Q, Levy DE, Dyck JA, Lu S, Sheiman LA, Liu Y. Proto-oncogene PML controls genes devoted to MHC class I antigen presentation [J]. Nature, 1998, 396: 373-376.
    [184] Larghero J, Zassadowski F, Rousselot P, Padua RA. Alteration of the PML proto-oncogene in leukemic cells does not abrogate expression of MHC class I antigens [J]. Leukaemia, 1999, 13: 1295-1296.
    [185] Wang ZG, Ruggero D, Ronchetti S, Zhong S, Gaboli M, RiviR, Pandolfi PP. PML is essential for multiple apoptotic pathways [J]. Nat Genet, 1998, 20: 266-272.
    [186] Wu WS, Xu ZX, Hittelman WN, Salomoni P, Pandolfi PP, Chang KS. Promyelocytic Leukemia Protein Sensitizes Tumor Necrosis Factorα-Induced Apoptosis by Inhibiting the NF-κB Survival Pathway [J]. J Biol Chem, 2003, 278: 12294-12304.
    [187] He LZ, Tribioli C, Rivi R, Peruzzi D, Soares V, Pelicci PG, Cattoretti G, Pandolfi PP. Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice [J]. Proc Natl Acad Sci USA, 1997, 94: 5302-5307.
    [188] Rego EM, Wang ZG, Peruzzi D, He LZ, Cordon-Cardo C, Pandolfi PP. Role of promyelocytic leukemia (PML) protein in tumor suppression [J]. J Exp Med, 2001, 23: 521-529.
    [189] Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC, de The′ H. PML induces a novel caspase-independent death process [J]. Nat Genet, 1998, 20: 259-265.
    [190] Rosa Bernardi1, Pier Paolo Pandolfi. Role of PML and the PML-nuclear body in the control of programmed cell death [J]. Oncogene, 2003, 22: 9048-9057
    [191] Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW. PML is induced by oncogenic ras and promotes premature senescence [J]. Genes Dev, 2000, 14: 2015-2027.
    [192] Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP, Pelicci PG. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras [J]. Nature, 2000, 406: 207-210.
    [193] Hanada K, Ukita T, Kohno Y, Saito K, Kato J, Ikeda H. Proc. RecQ DNA helicase is a suppressor of illegitimate recombination in Escherichia coli [J]. Proc Natl Acad Sci USA, 1997, 94: 3860-3865.
    [194] Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, Ciocci S, Proytcheva M, German J. The Bloom's syndrome gene product is homologous to RecQ helicases [J]. Cell, 1995, 83: 655-666.
    [195] Yankiwski V, Marciniak RA, Guarente L, Neff NF. Nuclear structure in normal and Bloom syndrome cells [J]. Proc Natl Acad Sci USA, 2000, 97: 5214-5219.
    [196] Bischof O, Kim SH, Irving J, Beresten S, Ellis NA, Campisi J. Regulation and localization of the Bloom syndrome protein in response to DNA damage [J]. J Cell Biol, 2001, 153: 367-380.
    [197] Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR. Telomere elongation in immortal human cells without detectable telomerase activity [J]. EMBO J, 1995,14: 4240-4248.
    [198] Yeager TR, Neumann AA, Englezou A, Huschtscha LI, Noble JR, Reddel RR. Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body [J]. Cancer Res, 1999, 59: 4175-4179.
    [199] Grobelny JV, Kulp-McEliece M, Broccoli D. Effects of reconstitution of telomerase activity on telomere maintenance by the alternative lengthening of telomeres (ALT) pathway [J]. Hum Mol Genet, 2001, 10: 1953-1961.
    [200] Dunham MA, Neumann AA, Fasching CL, Reddel RR. Telomere maintenance by recombination in human cells [J]. Nat Genet, 2000, 26: 447-450.
    [201] Rego E, Wang ZG, Peruzzi D, He LZ, Cordon-Cardo C, Pandolfi PP. Role of promyelocytic leukemia protein in tumor suppression [J]. J Exp Med, 2001, 193: 521-529.
    [202] Gurrieri C, Capodieci P, Bernardi R, Scaglioni PP, Nafa K, Rush LJ, Verbel DA, Cordon-Cardo C, Pandolfi PP. Loss of the tumor suppressor PML in human cancers of multiple histologic origins [J]. J Natl Cancer Inst, 2004, 96: 269-279.
    [203] ZimonjicDB, Pollok JL, Westervelt P, Popescu NC, Ley TJ. Acquired, nonrandom chromosomal abnormalities associated with the development of acute promyelocytic leukemia in transgenic mice [J]. PNAS USA, 2000, 97: 13306-13311
    [204] Le Beau MM, Davis EM, Patel B, Phan VT, Sohal J, Kogan SC. Recurring chromosomal abnormalities in leukemia in PML-RARA transgenic mice identify cooperating events and genetic pathways to acute promyelocytic leukemia [J]. Blood, 2003, 102: 1072-1074.
    [205] Liuh-Yow Chen, J. Don Chen. Daxx Silencing Sensitizes Cells to Multiple Apoptotic Pathways [J]. Mol Cel Bio, 2003, 23: 7108-7121.
    [206] Rui Y, Xu Z, Lin S, Li Q, Rui H, Luo W, Zhou HM, Cheung PY, Wu Z, Ye Z, Li P, Han J, Lin SC. Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation [J]. EMBO J, 2004, 23: 4583-4594.
    [207] Li Q, Wang X, Wu X, Rui Y, Liu W, Wang J, Wang X, Liou YC, Ye Z, Lin SC. Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death [J]. Cancer Res, 2007, 67: 66-74.
    [208] Hsu W, Shakya R, Costantini F. Impaired mammary gland and lymphoid development caused by inducible expression of Axin in transgenic mice [J]. J Cell Biol, 2001, 155: 1055-1064.
    [209] Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y, Nakamura Y. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1 [J]. Nat Genet, 2000, 24: 245-250.
    [210] el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent-JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a-potential mediator of p53 tumor suppression [J]. Cell, 1993, 75: 817-825.
    [211] Attardi LD, DePinho RA. Conquering the complexity of p53 [J]. Nat Genet, 2004, 36: 7-8.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700