BCL10调控粒—巨噬细胞集落刺激因子（GM-CSF）转录水平的研究
摘要
粒·巨噬细胞集落刺激因子(Granulocyte macrophage colony-stimulating factor,GM-CSF)是主要的造血生长因子之一,在造血调控和免疫调节中发挥重要作用。GM-CSF基因表达受转录水平和转录后水平调控,但主要受转录水平的调控。bcl10是从粘膜相关淋巴组织(mucosa-associated lymphoid tissue,MALT)淋巴瘤的染色体转位中发现的基因,这种染色体转位使整个bc110基因在染色体上受到Ig增强子的控制,进而导致其超量表达。BCL10在淋巴细胞抗原受体介导的NF-κB激活过程中是必需的,能调节细胞凋亡和NF-κB信号转导。本论文在构建含bcl10基因哺乳动物表达载体、构建GM-CSF启动子/增强子与luciferase嵌合载体、以及构建基于GM-CSF基础启动子的突变体(对GM-CSF基础启动子AP1、ETS1、NFAT、ETS1/NFAT转录因子作用位点的突变)的基础上,通过对白血病细胞株K526的转染,发现:
1)在K562细胞中,BCL10激活GM-CSF转录,Ionomycin促进BCL10对GM-CSF转录激活。
2)ETS1位点对于BCL10对GM-CSF的转录激活是必须的,细胞中正常水平的ETS1和AP1对GM-CSF的转录激活作用十分必要和重要,但细胞中过量的ETS1蛋白抑制BCL10对GM-CSF转录激活作用。
3)BCL10对GM-CSF的转录激活可能是通过一个独立于NF-κB途径进行的。
我们选取atxl基因的启动子作为研究对象。通过对启动子区域的5'和3'方向的缺失,构建了一系列表达载体,并转化Chlamydomonas reinharditii。通过对转化子的检测,确定了2处铁反应元件(FeREs)。即:AtxFeRE1在-529/-515(GTCGCACTGGCATGT)和AtxFeRE2在-300/-286(GCAGCGATGGCATTT)。二者有共同的序列:TGGCA.
Granulocyte macrophage colony-stimulating factor(GM-CSF)is a multipotent cytokine involved in the production and function of the hematopoietic cell.GM-CSF plays a major role in response to infection and physiological and pathological inflammatory processes.The expression of GM-CSF gene is controlled both in transcriptional and translational level,but primary regulated at transcriptional state.B-cell lymphoma 10(BCL10)gene was found in chromosomal dislocation in the cell of mucosa-associated lymphoid tissue(MALT)lymphoma. The chromosomal dislocation makes the bcl10 gene under the control of the enhancer of Ig, leading to over expression of bcl10.previous studies have shown that BCL10 involved in the activation of NF-κB signal pathway,and induce the cell apoptosis.In this study,on the base of producing the constructs including pcDNA1-BCL10,pGL2-GMCSFpr,pGL2-GMCSFpr/en, pGL2-GMCSFpr-basic,pGL2-GMCSFpr-mNFAT,pGL2-GMCSFpr-mETS1, pGL2-GMCSFpr-mAP1,and pGL2-GMCSFpr-mETS1/mNFAT,We transfer these plasmids to the cell of K562.The results demonstrate,
1)BCL10 activates the transcription of GM-CSF in K562,and improved by ionomycin.
2)The binding site of ETS1 is necessary for the transcriptional activation of GM-CSF by BCL10.The normal concentration of the ETS1 and AP1 are essential to the transcriptional activation of GM-CSF by BCL10,however,the over expression of ETS1 lead to repression of the transcriptional activation of GM-CSF by BCL10.
3)The transcriptional activation of GM-CSF by BCL10 is in a way independent from the NF-κB signal pathway.
We investigated the promoter region of atxl,which encodes a copper chaperone in response to iron deficiency induction.Deletion analysis of the promoter region from 5' and 3' ends revealed that the -532/-461 and -320 /-276 regions were necessary and sufficient for iron deficiency-inducible expression.Further deletion analysis showed that two of the Fe deficiency responsive elements(FeREs)localized within the -532/-511 and -306/-276 regions, in which AtxFeRE1 at -529/-515(GTCGCACTGGCATGT)and AtxFeRE2 at -300/-286 (GCAGCGATGGCATTT)had been identified respectively,with a conserved sequence of GNNGCNNTGGCATNT,differing from all known FeREs found in other organisms.
1)在K562细胞中,BCL10激活GM-CSF转录,Ionomycin促进BCL10对GM-CSF转录激活。
2)ETS1位点对于BCL10对GM-CSF的转录激活是必须的,细胞中正常水平的ETS1和AP1对GM-CSF的转录激活作用十分必要和重要,但细胞中过量的ETS1蛋白抑制BCL10对GM-CSF转录激活作用。
3)BCL10对GM-CSF的转录激活可能是通过一个独立于NF-κB途径进行的。
我们选取atxl基因的启动子作为研究对象。通过对启动子区域的5'和3'方向的缺失,构建了一系列表达载体,并转化Chlamydomonas reinharditii。通过对转化子的检测,确定了2处铁反应元件(FeREs)。即:AtxFeRE1在-529/-515(GTCGCACTGGCATGT)和AtxFeRE2在-300/-286(GCAGCGATGGCATTT)。二者有共同的序列:TGGCA.
Granulocyte macrophage colony-stimulating factor(GM-CSF)is a multipotent cytokine involved in the production and function of the hematopoietic cell.GM-CSF plays a major role in response to infection and physiological and pathological inflammatory processes.The expression of GM-CSF gene is controlled both in transcriptional and translational level,but primary regulated at transcriptional state.B-cell lymphoma 10(BCL10)gene was found in chromosomal dislocation in the cell of mucosa-associated lymphoid tissue(MALT)lymphoma. The chromosomal dislocation makes the bcl10 gene under the control of the enhancer of Ig, leading to over expression of bcl10.previous studies have shown that BCL10 involved in the activation of NF-κB signal pathway,and induce the cell apoptosis.In this study,on the base of producing the constructs including pcDNA1-BCL10,pGL2-GMCSFpr,pGL2-GMCSFpr/en, pGL2-GMCSFpr-basic,pGL2-GMCSFpr-mNFAT,pGL2-GMCSFpr-mETS1, pGL2-GMCSFpr-mAP1,and pGL2-GMCSFpr-mETS1/mNFAT,We transfer these plasmids to the cell of K562.The results demonstrate,
1)BCL10 activates the transcription of GM-CSF in K562,and improved by ionomycin.
2)The binding site of ETS1 is necessary for the transcriptional activation of GM-CSF by BCL10.The normal concentration of the ETS1 and AP1 are essential to the transcriptional activation of GM-CSF by BCL10,however,the over expression of ETS1 lead to repression of the transcriptional activation of GM-CSF by BCL10.
3)The transcriptional activation of GM-CSF by BCL10 is in a way independent from the NF-κB signal pathway.
We investigated the promoter region of atxl,which encodes a copper chaperone in response to iron deficiency induction.Deletion analysis of the promoter region from 5' and 3' ends revealed that the -532/-461 and -320 /-276 regions were necessary and sufficient for iron deficiency-inducible expression.Further deletion analysis showed that two of the Fe deficiency responsive elements(FeREs)localized within the -532/-511 and -306/-276 regions, in which AtxFeRE1 at -529/-515(GTCGCACTGGCATGT)and AtxFeRE2 at -300/-286 (GCAGCGATGGCATTT)had been identified respectively,with a conserved sequence of GNNGCNNTGGCATNT,differing from all known FeREs found in other organisms.
引文
Bertin J., Lin W., Yin G., Jacobson M.D. et al. CARD11 and CARD14 are novel caspase recruitment domain(CARD)/membrane-associated guanylate kinase(MAGUK) family members that interact with BCLIO and activated NF-kB. J. Biol. Chem. 2001, 276:11877-11882
Du M. Q., Peng H., Liu H., Hamoudi R.A. et al. BCLIO gene mutation in lymohona. Blood. 2000, 95:3885-3890
Eliyahu D., Michalovitz D., Eliyahu S. et al. Wild type p53 can inhibit oncogene-mediated focus formation. Proc. Natl. Acad. Sci. USA. 1989, 86:8763-8767
Gaide O., Martinon F., Micheau O. et al. Carmal, a CARD-containing binding partner of BCL10, induces BCL10 phosphorylation and NF-kB activation. FEBS lett. 2001,496:121-127
Gasson J. C. Molecular Physiology of GranulocyteMacrophage Colony-Stimulating Factor. Blood. 1991,77:1131-1142.
Gerondakis S., Strasser A., Metca F. D. et al. Rel-deficient T Cells Exhibit Defects in Production of lnterleukin 3 and Granulocyte-Macrophage Colon)'-Stimulating Factor. Proc Natl Acad Sci USA.1996, 93: 3405 3409.
Gill S., Broni J., Jefferies S. et al. BCL10 is rarely mutated in human prostate carcinoma, small-cell lung cancer, head and necks tumors, renal carcinoma and sarcomas. British journal of cancer. 1999, 80:1565-1568
Hliang T., Ren-Feng Guo, Kari A., Dilley. et al. Molecular cloning and characterization of DEFCA-land-s, two isoforms of a novel member of the mammalian ced-4 family of apoptosis proteins. J. Biol. Chem. 2001, 276:9230-9238
Hofmann K., Bucher P., Tschopp J. et al. The CARD domain: a new apoptotic signaling motif. Trends Biochem. Science. 1997,22:155-156
Isaacson P.G. and Spencer J. The biology of low-grade MALT lymphomas. J. Clin. Pathol. 1995, 48:395-397
Lambers A.R., Gumbs C., Ali S. et al. BCL10 is not a target for frequent mutation in human carcinomas. British journal of cancer. 1999, 80:1575-1576
Lee S. H., Shin M. S, Kim H. S. et al. Point mutations and deletions of the BCL10 gene in solid tumors and malignant lymphomas. Cancer research. 1999,59:5674-5677
Lucas P.C., yonezumi M., Inohara N., et al. Nunes G. BCLIO and MALT1. Independent Targets of Chromosomal Translacation in MALT lymphoma, Cooperate in a Novel NF-κB signaling pathway. J. Biol. Chem. 2001, 276:19012-19019
Magrath, I. T. The pathogenesis of Burkitt's lymphoma. Adv. Cancer Res. 1990, 50:133-270
Rabbitts T. H., Hamlym P. H., Baer R. et al. Altered nucleotide sequences of a translocatin c-myc. gene in Burkitt lymphoma. Nature. 1983, 306:760-765
Ruland J., Gordon S., Duncan A. E. et al. Regulatory mechanisms of TRAF2-mediated signal transduction by BCL10, a MALT lymphoma-associated protein. J. Biol. Chem. 2000, 275:11114-11120
Sen R., Baltimore D. Inducibility of t he immunuglobulin enhanc2 erbinding protein NF - kB by a posit ranslational mechanism. Cell.1986 ,47 :921 - 928
Thompson J. E., Phillips R. J., Erdjument B. H. et al. 1 kappa B - beta regulates t he persistent response in a biphasic activation of NF - kappa B. Cell.1995 ,80 (4) :573 - 582
Tsujimoto Y., Finger L. R., Yunis J. et al. Cloning of the chromosome breakpoint of neoplasitic B cells with the 1114:181 chromosome translocation. Science. 1984, 226: 1097-1099
Vaandrager J. W., Schuuring E., Zwikstra E. et al. Direct visulization of dispersed 11q13 chromosomal translocation in mantle cell lymphoma by multicolour DNA fiber fluorescene in situ hybridization. Blood. 1996, 88:1172-1182
Wang L., Guo Y., Huang W. J. et al. CARD10 is a novel caspase recruiment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kB. J. Biol. Chem. 2001,276:19012-19019
Willis T.G., Dalai M., Du M. Q. et al. BCL10 is involved in t(1:14Xp22:q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell. 1999,96:35-45
Wotherspoon A.C., Pan L. X., Diss T. C. et al. Cytogenetic study of B-cell lymophoma of mucosa-associated lymphoma tissue. Cancer genet. Cytogenet. 1992, 58;35-38
Xue L. Q., Morris S. W., Oribuela C. et al. Defective development and function of BCL10 deficient follicular, marginal zone and B1 B cells. Nat. Immunol. 2003,4:857-865
Yan M, Lee J., Schilbach S. et al. mE10, a novel caspase recruiment domain-containing proapoptotic molecule. J. Biol. Chem. 1999, 274 :10.287
Ye.H.T.,Dogan A.,Karran L.et al.BCL10 expression in normal and neoplastic lymphoid tissue.Amrican Journal of Pathology.2000,157:1147-1154
Yui D.,Yoneda T.,Oono K.et al.Interohargeable binding of BCL10 to TRAF2 and clAPs regulates apoptosis signaling.Oncogenge.2001,20:4317-4323
Zhang M.Y.,Sun S.C.,Bell L.et al.NF-κB Transcription Factors Are in Normal Erythropoiesis.Blood.1998,91:4136-4144
蒋叶。核转录因子-κB信号通路在内毒素致急性肺损伤中的作用。中国急救医学,2004,24:902-904
林振和。核因子-κB信号转导途径的调节研究进展。国外医学免疫学分册,2004,27:234-238
毛华,陈秘森,粱植权。GM CSF基因调控及其功能研究进展。国外医学免疫学手册,1998,21:249-252
王绮如,汪保和,夏晖。粒巨噬细胞集落刺激目子对小鼠骨髓内皮细胞坩殖的刺激作用。中华血液学杂志,1998,19:320 321
王文珊。TNF-a信号转导通路的研究进展。福建医科大学学报,2005,39:27-31
吴丽娟,蒋建新,朱佩芳等。NF-κB信号转导途径研究进展。国外医学临床生物化学与检验学分册,2002,23:260-262
邢飞跃,赵克森,姜勇。NF-κB的信号通路与阻断策略。中国病理生理杂志,2003,19:849-855
尹会男,柴家科。Toll样受体/核因子κB信号通路与脓毒症的研究进展。中华实验外科杂志,2003,20:1 051-1 052
张劲松,王兴宇,单佑安等。转录因子NF-κB的研究进展。科学通报,2002,47:323-329
Askwith C., and Kaplan J. (1997) An oxidase-permease-based iron transport system in Schizosaccharomyces pombe and its expression in Saccharomyces cerevisiae. Journal of Biological Chemistry 272, 401-405.
Askwith C., Eide D., Van Ho A., Bernard P.S., Li L., Davis-Kaplan S., Sipe D.M., and Kaplan J. (1994). The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake. Cell 76, 403-410.
Brumbarova T. and Bauer P. (2005) Iron-mediated control of the basic helix-loop-helix protein FER, a regulator of iron uptake in tomato. Plant Physiology 137,1018-1026.
Davies J. P., Grossman A. R. (1994) Sequences controlling transcription of the Chlamydomonas reinhardtii beta 2-tubulin gene after deflagellation and during the cell cycle. Molecular Cell Biology 14,5165-5174.
Davies J. P., Weeks D. P., & Grossman A. R. (1992) Expression of the arylsulfatase gene from the beta 2-tubulin promoter in Chlamydomonas reinhardtii. Nucleic Acids Research 20, 2959-2965.
Debuchy R., Purton S.& Rochaix J. D. (1989) The argininosuccinate lyase gene of Chlamydomonas reinhardtii: an important tool for nuclear transformation and for correlating the genetic and molecular maps of the ARG7 locus. EMBO Journal 8,2803-2809.
De Hostos E. L., Togasaki R. K. & Grossman A. (1988) Purification and biosynthesis of a derepressible periplasmic arylsulfatase from Chlamydomonas reinhardtii.The Journal of Cell Biology 106,29-37.
De Lorenzo V.,Wee,S.,Herrero,M.& Neilands,J.B.(1987)Operator sequences of the aerobactin operon of plasmid ColV-K30 binding the ferric uptake regulation(fur)repressor.The Journal of Bacteriology 169,2624-2630.
Dix D.R.,Bridgham J.T.,Broderius M.A.,Byersdorfer C.A.& Eide,D.J.(1994)The FET4 gene encodes the low affinity Fe(Ⅱ)transport protein of Saccharomyces cerevisiae.Journal of Biological Chemistry 269,26092-26099.
Dix D.,Bridgham J.,Broderius M.& Eide D.(1997)Characterization of the FET4 protein of yeast.Evidence for a direct role in the transport of iron.Journal of Biological Chemistry 272,11770-11777.
Eckhardt U.& Buckhout T.J.(1998)Iron assimilation in Chlamydomonas reinhardtii involves ferric reduction and is similar to Strategy I higher plants.Journal of Experimental Botany 49,1219-1226.
Eide D.,Broderius M.,Fett J.& Guerinot M.L.(1996)A novel ironregulated metal transporter from plants identified by functional expression in yeast.Proceedings of the National Academy of Sciences 93,5624-5628.
Guerinot M.L.(2000)The ZIP family of metal transporters.Biochimica et Biophysica Acta 1465,190-198.
Hanikenne M.,Kramer U.,Demoulin V.& Baurain D.(2005)A comparative inventory of metal transporters in the green alga Chlamydomonas reinhardtii and the red alga Cyanidioschizon merolae.Plant Physiology 137,428-446.
Hassett R.,Dix D.R.,Eide D.J.& Kosman D.J.(2000)The Fe(Ⅱ)permease Fet4p functions as a low affinity copper transporter and supports normal copper trafficking in accharomyces cerevisiae.Biochemical Journal 351,477-484.
Herbik A.,Boiling C.,& Buckhout T.J.(2002)The involvement of a multicopper oxidase in iron uptake by the green algae Chlamydomonas reinhardtii.Plant Physiology 130,2039-2048.
Kindle K.L.(1990)High frequency nuclear transformation of Chlamydomonas reinhardtii.Proceedings of the National Academy of Sciences 87,1228-1232.
Kobayashi T.,Nakayama Y.,Itai R.N.,Nakanishi H.,Yoshihara T.,Mori S.& Nishizawa N.K.(2003)Identification of novel cis-acting elements,IDE1 and IDE2,of the barley IDS2 gene promoter conferring iron-deficiency-inducible,root-specific expression in heterogeneous tobacco plants.Plant Journal 36,780-793.
Korshunova Y.,Eide D.,Clark W.G.,Guerinot M.L & Pakrasi H.B.(1999)The IRT1 protein from Arabidopsis thaliana is a metal transporter with a broad substrate range.Plant Molecular Biology 40,37-44.
La Fontaine S.,Quinn J.M.,Nakamoto S.S.,Page M.D.,Gohre V.,Moseley J.L.,Kropat J.& Merchant S.(2002)Copper-Dependent Iron Assimilation Pathway in the Model Photosynthetic Eukaryote Chlamydomonas reinhardtii.Eukaryotic Cell 1,736-757.
Lin S.J.,Pufahl R.A.,Dancis A.,O'Halloran T.V.& Culotta V.C.(1997).A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport.Journal of Biological Chemistry 272,9215-9220.
Ling H.Q.,Bauer P.,Bereczky Z.,Keller B.& Ganal M.(2002)The tomato fer gene encoding a bHLH protein controls iron-uptake responses in roots.Proceedings of the National Academy of Sciences 99,13938-13943.
Livak K.J.& Schmittgen T.D.(2001)Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))Method.Methods 25,402-408.
Martins L.J.,Jensen L.T.,Simons J.R.,Keller G.L.& Winge D.R.(1998)Metalloregulation of FRE1 and FRE2homologs in Saccharomyces cerevisiae.Journal of Biological Chemistry 273,23716-23721.
Okumura N.,Nishizawa N.K.,Umehara Y.& Mori S.(1991)An iron deficiency-specific cDNA from barley roots having two homologous cysteine-rich MT domains.Plant Molecular Biology 17,531-533.
Okumura N.,Nishizawa N.K.,Umehara Y.,Ohata T.,Nakanishi H.,Yamaguchi H.,Chino M.& Mori S.(1994)A dioxygenase gene(Ids2)expressed under iron deficiency conditions in the roots of Hordeum vulgate.Plant Molecular Biology 25,705-719.
Petit J.M.,van Wuytswinkel O.,Briat J.F & Lobréaux S.(2001)Characterization of an iron-dependent regulatory sequence involved in the transcriptional control of Atfer1 and Zmfer1 plant ferritin genes by iron.Journal of Biological Chemistry 276,5584-5590.
Radisky D.& Kaplan J.(1999)Regulation of transition metal transport across the yeast plasma membrane.Journal of Biological Chemistry 274,4481-4484.
Robinson N.J.,Procter C.M.,Connolly E.L.& Guerinot M.L.(1999)A ferric-chelate reductase for iron uptake from soils.Nature 397,694-697.
Romheld V.& Marchner H.(1986)Evidence for a specific uptake system for iron phytosiderophores in roots of grasses.Plant Physiology 80,175-180.
Rubinelli P.,Siripornadulsil S.,Gao-Rubinelli F.& Sayre R.T.(2002)Cadmium- and iron-stress-inducible gene expression in the green alga Chlamydomonas reinhardtii:evidence for H43 protein function in iron assimilation.Planta 215,1-13.
Rutherford J.C.,Jaron S.& Winge D.R.(2003)Aft1p and Aft2p mediate iron-responsive gene expression in yeast through related promoter elements.Journal of Biological Chemistry 278,27636-27643.
Rutherford J.C.& A.J.Bird.(2004).Metal-responsive transcription factors that regulate iron,zinc,and copper homeostasis in eukaryotic cells.Eukaryotic Cell 3,1-13.
Stearman R.,Yuan D.S.,Yamaguchi-Iwai Y.,Klausner R.D.& Dancis A.(1996)A permease-oxidase complex involved in high-affinity iron uptake in yeast.Science 271,1552-1557.
Straus N.A.(1994)Iron deprivation:physiology and gene regulation.In The Molecular Biology of Cyanobacteria (Briant,D.A.,ed.).Dordrecht,the Netherlands:Kluwer Academic Publishers,pp.731-750.
Takagi S.,Nomoto K.& Takemoto T.(1984)Physiologican aspects of muginic acid,a possible phytosiderophore graminaceous plants.Journal of Plant Nutrition 7,469-477.
Theil E.C.(1990)Regulation of ferritin and transferin receptor mRNAs.Journal of Biological Chemistry 265,4771-4774.
Vert G.,Briat J.F.& Curie C.(2001).Arabidopsis IRT2 gene encodes a root-periphery iron transporter.Plant Journal 26,181-189.
Wei J.& Theil E.C.(2000)Identification and characterization of the iron regulatory element in the ferritin gene of a plant(soybean).Journal of Biological Chemistry 275,17488-17493.
Du M. Q., Peng H., Liu H., Hamoudi R.A. et al. BCLIO gene mutation in lymohona. Blood. 2000, 95:3885-3890
Eliyahu D., Michalovitz D., Eliyahu S. et al. Wild type p53 can inhibit oncogene-mediated focus formation. Proc. Natl. Acad. Sci. USA. 1989, 86:8763-8767
Gaide O., Martinon F., Micheau O. et al. Carmal, a CARD-containing binding partner of BCL10, induces BCL10 phosphorylation and NF-kB activation. FEBS lett. 2001,496:121-127
Gasson J. C. Molecular Physiology of GranulocyteMacrophage Colony-Stimulating Factor. Blood. 1991,77:1131-1142.
Gerondakis S., Strasser A., Metca F. D. et al. Rel-deficient T Cells Exhibit Defects in Production of lnterleukin 3 and Granulocyte-Macrophage Colon)'-Stimulating Factor. Proc Natl Acad Sci USA.1996, 93: 3405 3409.
Gill S., Broni J., Jefferies S. et al. BCL10 is rarely mutated in human prostate carcinoma, small-cell lung cancer, head and necks tumors, renal carcinoma and sarcomas. British journal of cancer. 1999, 80:1565-1568
Hliang T., Ren-Feng Guo, Kari A., Dilley. et al. Molecular cloning and characterization of DEFCA-land-s, two isoforms of a novel member of the mammalian ced-4 family of apoptosis proteins. J. Biol. Chem. 2001, 276:9230-9238
Hofmann K., Bucher P., Tschopp J. et al. The CARD domain: a new apoptotic signaling motif. Trends Biochem. Science. 1997,22:155-156
Isaacson P.G. and Spencer J. The biology of low-grade MALT lymphomas. J. Clin. Pathol. 1995, 48:395-397
Lambers A.R., Gumbs C., Ali S. et al. BCL10 is not a target for frequent mutation in human carcinomas. British journal of cancer. 1999, 80:1575-1576
Lee S. H., Shin M. S, Kim H. S. et al. Point mutations and deletions of the BCL10 gene in solid tumors and malignant lymphomas. Cancer research. 1999,59:5674-5677
Lucas P.C., yonezumi M., Inohara N., et al. Nunes G. BCLIO and MALT1. Independent Targets of Chromosomal Translacation in MALT lymphoma, Cooperate in a Novel NF-κB signaling pathway. J. Biol. Chem. 2001, 276:19012-19019
Magrath, I. T. The pathogenesis of Burkitt's lymphoma. Adv. Cancer Res. 1990, 50:133-270
Rabbitts T. H., Hamlym P. H., Baer R. et al. Altered nucleotide sequences of a translocatin c-myc. gene in Burkitt lymphoma. Nature. 1983, 306:760-765
Ruland J., Gordon S., Duncan A. E. et al. Regulatory mechanisms of TRAF2-mediated signal transduction by BCL10, a MALT lymphoma-associated protein. J. Biol. Chem. 2000, 275:11114-11120
Sen R., Baltimore D. Inducibility of t he immunuglobulin enhanc2 erbinding protein NF - kB by a posit ranslational mechanism. Cell.1986 ,47 :921 - 928
Thompson J. E., Phillips R. J., Erdjument B. H. et al. 1 kappa B - beta regulates t he persistent response in a biphasic activation of NF - kappa B. Cell.1995 ,80 (4) :573 - 582
Tsujimoto Y., Finger L. R., Yunis J. et al. Cloning of the chromosome breakpoint of neoplasitic B cells with the 1114:181 chromosome translocation. Science. 1984, 226: 1097-1099
Vaandrager J. W., Schuuring E., Zwikstra E. et al. Direct visulization of dispersed 11q13 chromosomal translocation in mantle cell lymphoma by multicolour DNA fiber fluorescene in situ hybridization. Blood. 1996, 88:1172-1182
Wang L., Guo Y., Huang W. J. et al. CARD10 is a novel caspase recruiment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kB. J. Biol. Chem. 2001,276:19012-19019
Willis T.G., Dalai M., Du M. Q. et al. BCL10 is involved in t(1:14Xp22:q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell. 1999,96:35-45
Wotherspoon A.C., Pan L. X., Diss T. C. et al. Cytogenetic study of B-cell lymophoma of mucosa-associated lymphoma tissue. Cancer genet. Cytogenet. 1992, 58;35-38
Xue L. Q., Morris S. W., Oribuela C. et al. Defective development and function of BCL10 deficient follicular, marginal zone and B1 B cells. Nat. Immunol. 2003,4:857-865
Yan M, Lee J., Schilbach S. et al. mE10, a novel caspase recruiment domain-containing proapoptotic molecule. J. Biol. Chem. 1999, 274 :10.287
Ye.H.T.,Dogan A.,Karran L.et al.BCL10 expression in normal and neoplastic lymphoid tissue.Amrican Journal of Pathology.2000,157:1147-1154
Yui D.,Yoneda T.,Oono K.et al.Interohargeable binding of BCL10 to TRAF2 and clAPs regulates apoptosis signaling.Oncogenge.2001,20:4317-4323
Zhang M.Y.,Sun S.C.,Bell L.et al.NF-κB Transcription Factors Are in Normal Erythropoiesis.Blood.1998,91:4136-4144
蒋叶。核转录因子-κB信号通路在内毒素致急性肺损伤中的作用。中国急救医学,2004,24:902-904
林振和。核因子-κB信号转导途径的调节研究进展。国外医学免疫学分册,2004,27:234-238
毛华,陈秘森,粱植权。GM CSF基因调控及其功能研究进展。国外医学免疫学手册,1998,21:249-252
王绮如,汪保和,夏晖。粒巨噬细胞集落刺激目子对小鼠骨髓内皮细胞坩殖的刺激作用。中华血液学杂志,1998,19:320 321
王文珊。TNF-a信号转导通路的研究进展。福建医科大学学报,2005,39:27-31
吴丽娟,蒋建新,朱佩芳等。NF-κB信号转导途径研究进展。国外医学临床生物化学与检验学分册,2002,23:260-262
邢飞跃,赵克森,姜勇。NF-κB的信号通路与阻断策略。中国病理生理杂志,2003,19:849-855
尹会男,柴家科。Toll样受体/核因子κB信号通路与脓毒症的研究进展。中华实验外科杂志,2003,20:1 051-1 052
张劲松,王兴宇,单佑安等。转录因子NF-κB的研究进展。科学通报,2002,47:323-329
Askwith C., and Kaplan J. (1997) An oxidase-permease-based iron transport system in Schizosaccharomyces pombe and its expression in Saccharomyces cerevisiae. Journal of Biological Chemistry 272, 401-405.
Askwith C., Eide D., Van Ho A., Bernard P.S., Li L., Davis-Kaplan S., Sipe D.M., and Kaplan J. (1994). The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake. Cell 76, 403-410.
Brumbarova T. and Bauer P. (2005) Iron-mediated control of the basic helix-loop-helix protein FER, a regulator of iron uptake in tomato. Plant Physiology 137,1018-1026.
Davies J. P., Grossman A. R. (1994) Sequences controlling transcription of the Chlamydomonas reinhardtii beta 2-tubulin gene after deflagellation and during the cell cycle. Molecular Cell Biology 14,5165-5174.
Davies J. P., Weeks D. P., & Grossman A. R. (1992) Expression of the arylsulfatase gene from the beta 2-tubulin promoter in Chlamydomonas reinhardtii. Nucleic Acids Research 20, 2959-2965.
Debuchy R., Purton S.& Rochaix J. D. (1989) The argininosuccinate lyase gene of Chlamydomonas reinhardtii: an important tool for nuclear transformation and for correlating the genetic and molecular maps of the ARG7 locus. EMBO Journal 8,2803-2809.
De Hostos E. L., Togasaki R. K. & Grossman A. (1988) Purification and biosynthesis of a derepressible periplasmic arylsulfatase from Chlamydomonas reinhardtii.The Journal of Cell Biology 106,29-37.
De Lorenzo V.,Wee,S.,Herrero,M.& Neilands,J.B.(1987)Operator sequences of the aerobactin operon of plasmid ColV-K30 binding the ferric uptake regulation(fur)repressor.The Journal of Bacteriology 169,2624-2630.
Dix D.R.,Bridgham J.T.,Broderius M.A.,Byersdorfer C.A.& Eide,D.J.(1994)The FET4 gene encodes the low affinity Fe(Ⅱ)transport protein of Saccharomyces cerevisiae.Journal of Biological Chemistry 269,26092-26099.
Dix D.,Bridgham J.,Broderius M.& Eide D.(1997)Characterization of the FET4 protein of yeast.Evidence for a direct role in the transport of iron.Journal of Biological Chemistry 272,11770-11777.
Eckhardt U.& Buckhout T.J.(1998)Iron assimilation in Chlamydomonas reinhardtii involves ferric reduction and is similar to Strategy I higher plants.Journal of Experimental Botany 49,1219-1226.
Eide D.,Broderius M.,Fett J.& Guerinot M.L.(1996)A novel ironregulated metal transporter from plants identified by functional expression in yeast.Proceedings of the National Academy of Sciences 93,5624-5628.
Guerinot M.L.(2000)The ZIP family of metal transporters.Biochimica et Biophysica Acta 1465,190-198.
Hanikenne M.,Kramer U.,Demoulin V.& Baurain D.(2005)A comparative inventory of metal transporters in the green alga Chlamydomonas reinhardtii and the red alga Cyanidioschizon merolae.Plant Physiology 137,428-446.
Hassett R.,Dix D.R.,Eide D.J.& Kosman D.J.(2000)The Fe(Ⅱ)permease Fet4p functions as a low affinity copper transporter and supports normal copper trafficking in accharomyces cerevisiae.Biochemical Journal 351,477-484.
Herbik A.,Boiling C.,& Buckhout T.J.(2002)The involvement of a multicopper oxidase in iron uptake by the green algae Chlamydomonas reinhardtii.Plant Physiology 130,2039-2048.
Kindle K.L.(1990)High frequency nuclear transformation of Chlamydomonas reinhardtii.Proceedings of the National Academy of Sciences 87,1228-1232.
Kobayashi T.,Nakayama Y.,Itai R.N.,Nakanishi H.,Yoshihara T.,Mori S.& Nishizawa N.K.(2003)Identification of novel cis-acting elements,IDE1 and IDE2,of the barley IDS2 gene promoter conferring iron-deficiency-inducible,root-specific expression in heterogeneous tobacco plants.Plant Journal 36,780-793.
Korshunova Y.,Eide D.,Clark W.G.,Guerinot M.L & Pakrasi H.B.(1999)The IRT1 protein from Arabidopsis thaliana is a metal transporter with a broad substrate range.Plant Molecular Biology 40,37-44.
La Fontaine S.,Quinn J.M.,Nakamoto S.S.,Page M.D.,Gohre V.,Moseley J.L.,Kropat J.& Merchant S.(2002)Copper-Dependent Iron Assimilation Pathway in the Model Photosynthetic Eukaryote Chlamydomonas reinhardtii.Eukaryotic Cell 1,736-757.
Lin S.J.,Pufahl R.A.,Dancis A.,O'Halloran T.V.& Culotta V.C.(1997).A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport.Journal of Biological Chemistry 272,9215-9220.
Ling H.Q.,Bauer P.,Bereczky Z.,Keller B.& Ganal M.(2002)The tomato fer gene encoding a bHLH protein controls iron-uptake responses in roots.Proceedings of the National Academy of Sciences 99,13938-13943.
Livak K.J.& Schmittgen T.D.(2001)Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))Method.Methods 25,402-408.
Martins L.J.,Jensen L.T.,Simons J.R.,Keller G.L.& Winge D.R.(1998)Metalloregulation of FRE1 and FRE2homologs in Saccharomyces cerevisiae.Journal of Biological Chemistry 273,23716-23721.
Okumura N.,Nishizawa N.K.,Umehara Y.& Mori S.(1991)An iron deficiency-specific cDNA from barley roots having two homologous cysteine-rich MT domains.Plant Molecular Biology 17,531-533.
Okumura N.,Nishizawa N.K.,Umehara Y.,Ohata T.,Nakanishi H.,Yamaguchi H.,Chino M.& Mori S.(1994)A dioxygenase gene(Ids2)expressed under iron deficiency conditions in the roots of Hordeum vulgate.Plant Molecular Biology 25,705-719.
Petit J.M.,van Wuytswinkel O.,Briat J.F & Lobréaux S.(2001)Characterization of an iron-dependent regulatory sequence involved in the transcriptional control of Atfer1 and Zmfer1 plant ferritin genes by iron.Journal of Biological Chemistry 276,5584-5590.
Radisky D.& Kaplan J.(1999)Regulation of transition metal transport across the yeast plasma membrane.Journal of Biological Chemistry 274,4481-4484.
Robinson N.J.,Procter C.M.,Connolly E.L.& Guerinot M.L.(1999)A ferric-chelate reductase for iron uptake from soils.Nature 397,694-697.
Romheld V.& Marchner H.(1986)Evidence for a specific uptake system for iron phytosiderophores in roots of grasses.Plant Physiology 80,175-180.
Rubinelli P.,Siripornadulsil S.,Gao-Rubinelli F.& Sayre R.T.(2002)Cadmium- and iron-stress-inducible gene expression in the green alga Chlamydomonas reinhardtii:evidence for H43 protein function in iron assimilation.Planta 215,1-13.
Rutherford J.C.,Jaron S.& Winge D.R.(2003)Aft1p and Aft2p mediate iron-responsive gene expression in yeast through related promoter elements.Journal of Biological Chemistry 278,27636-27643.
Rutherford J.C.& A.J.Bird.(2004).Metal-responsive transcription factors that regulate iron,zinc,and copper homeostasis in eukaryotic cells.Eukaryotic Cell 3,1-13.
Stearman R.,Yuan D.S.,Yamaguchi-Iwai Y.,Klausner R.D.& Dancis A.(1996)A permease-oxidase complex involved in high-affinity iron uptake in yeast.Science 271,1552-1557.
Straus N.A.(1994)Iron deprivation:physiology and gene regulation.In The Molecular Biology of Cyanobacteria (Briant,D.A.,ed.).Dordrecht,the Netherlands:Kluwer Academic Publishers,pp.731-750.
Takagi S.,Nomoto K.& Takemoto T.(1984)Physiologican aspects of muginic acid,a possible phytosiderophore graminaceous plants.Journal of Plant Nutrition 7,469-477.
Theil E.C.(1990)Regulation of ferritin and transferin receptor mRNAs.Journal of Biological Chemistry 265,4771-4774.
Vert G.,Briat J.F.& Curie C.(2001).Arabidopsis IRT2 gene encodes a root-periphery iron transporter.Plant Journal 26,181-189.
Wei J.& Theil E.C.(2000)Identification and characterization of the iron regulatory element in the ferritin gene of a plant(soybean).Journal of Biological Chemistry 275,17488-17493.