EZH2

组蛋白-離氨酸N-甲基转移酶EZH2是一个由人类EZH2基因所编码的酶。已鉴定该基因转录出的两种转录物变异体编码不同的亚型。 该基因编码的蛋白属于多梳家族（PcG）成员。PcG家族成员相互结合形成多聚蛋白复合物，这种复合物涉及到在细胞世代间维持基因的转录抑制状态。EZH2主要通过将三个甲基基团加到组蛋白3的27号赖氨酸（H3K27）上行使基因沉默者的角色，三甲基化H3K27是维持染色质凝聚的一种重要修饰。 该蛋白与胚胎外胚层发育蛋白（EED）、癌蛋白VAV1和X连锁核蛋白（XNP）之间关系密切。EZH2蛋白可能在造血系统和中枢神经系统中起到重要作用。 EZH2基因中的突变导致韦弗综合征。miR-101在正常情况下阻止编码EZH2的mRNA进入翻译阶段。因此这一微RNA的基因一旦缺失就会导致产生过量的EZH2。EZH2过多表达可能导致癌症形成，这是因为过多地组蛋白甲基化抑癌基因将导致其表达沉默。一种靶向EZH2药物的临床前模型显示其能够抑制脑癌及前列腺癌的进展。 EZH2与下列蛋白质有着蛋白質交互作用：ATRX、EED、HDAC1、HDAC2引用错误：<ref>标签有衝突或無效的属性和VAV1。 Chen H, Rossier C, Antonarakis SE. Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2. Genomics. Mar 1997, 38 (1): 30–7. PMID 8954776. doi:10.1006/geno.1996.0588.  Fiskus W, Pranpat M, Balasis M, Herger B, Rao R, Chinnaiyan A, Atadja P, Bhalla K. Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells. Mol Cancer Ther. Dec 2006, 5 (12): 3096–104. PMID 17172412. doi:10.1158/1535-7163.MCT-06-0418.  Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila). （原始内容存档于2019-10-16）.  Ru Cao, Liangjun Wang, Hengbin Wang, Li Xia, Hediye Erdjument-Bromage, Paul Tempst, Richard S Jones, Yi Zhang. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. NOV 2002, 298 (5595): 1039–43. PMID 12351676. doi:10.1126/science.1076997.  请检查|date=中的日期值 (帮助) Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA, Chitayat D, Boycott KM, Weaver DD, Jones SJ. Mutations in EZH2 Cause Weaver Syndrome. Am J Hum Genet. December 2011, 90 (1): 110–8. PMID 22177091. doi:10.1016/j.ajhg.2011.11.018.  Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, Noske DP, Tannous BA, Würdinger T. miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget. December 2010, 1 (8): 710–20. PMC 3124376 . PMID 21321380.  Suvà ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L, Marquez VE, Clément V, Stamenkovic I. EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res. December 2009, 69 (24): 9211–8. PMID 19934320. doi:10.1158/0008-5472.CAN-09-1622.  Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, Danesi R, Farrar WL. Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. Mol. Cancer. 2011, 10: 40. PMC 3100246 . PMID 21501485. doi:10.1186/1476-4598-10-40.  Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L. Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein. Hum. Mol. Genet. April 1998, 7 (4): 679–84. PMID 9499421. doi:10.1093/hmg/7.4.679.  van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E. Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes. Mol. Cell. Biol. June 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.  Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. Point mutations in the WD40 domain of Eed block its interaction with Ezh2. Mol. Cell. Biol. October 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.  van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat. Genet. December 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.  Hobert O, Jallal B, Ullrich A. Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression. Mol. Cell. Biol. June 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.  Zeidler M, Kleer CG. The Polycomb group protein Enhancer of Zeste 2: its links to DNA repair and breast cancer.. J. Mol. Histol. 2007, 37 (5-7): 219–23. PMID 16855786. doi:10.1007/s10735-006-9042-9.  De Haan G, Gerrits A. Epigenetic control of hematopoietic stem cell aging the case of Ezh2.. Ann. N. Y. Acad. Sci. 2007, 1106 (1): 233–9. PMID 17332078. doi:10.1196/annals.1392.008.  Hobert O, Jallal B, Ullrich A. Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression.. Mol. Cell. Biol. 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.  Bonaldo MF, Lennon G, Soares MB. Normalization and subtraction: two approaches to facilitate gene discovery.. Genome Res. 1997, 6 (9): 791–806. PMID 8889548. doi:10.1101/gr.6.9.791.  Abel KJ, Brody LC, Valdes JM; et al. Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1.. Genomics. 1997, 37 (2): 161–71. PMID 8921387. doi:10.1006/geno.1996.0537.  引文格式1维护：显式使用等标签 (link) Laible G, Wolf A, Dorn R; et al. Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres.. EMBO J. 1997, 16 (11): 3219–32. PMC 1169939 . PMID 9214638. doi:10.1093/emboj/16.11.3219.  引文格式1维护：显式使用等标签 (link) Cardoso C, Timsit S, Villard L; et al. Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein.. Hum. Mol. Genet. 1998, 7 (4): 679–84. PMID 9499421. doi:10.1093/hmg/7.4.679.  引文格式1维护：显式使用等标签 (link) van Lohuizen M, Tijms M, Voncken JW; et al. Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes.. Mol. Cell. Biol. 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.  引文格式1维护：显式使用等标签 (link) Sewalt RG, van der Vlag J, Gunster MJ; et al. Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes.. Mol. Cell. Biol. 1998, 18 (6): 3586–95. PMC 108940 . PMID 9584199.  引文格式1维护：显式使用等标签 (link) Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. Point mutations in the WD40 domain of Eed block its interaction with Ezh2.. Mol. Cell. Biol. 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.  van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation.. Nat. Genet. 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.  Cardoso C, Mignon C, Hetet G; et al. The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.. Eur. J. Hum. Genet. 2000, 8 (3): 174–80. PMID 10780782. doi:10.1038/sj.ejhg.5200439.  引文格式1维护：显式使用等标签 (link) Raaphorst FM, Otte AP, van Kemenade FJ; et al. Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation.. J. Immunol. 2001, 166 (10): 5925–34. PMID 11342607.  引文格式1维护：显式使用等标签 (link) O'Connell S, Wang L, Robert S; et al. Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein.. J. Biol. Chem. 2001, 276 (46): 43065–73. PMID 11571280. doi:10.1074/jbc.M104294200.  引文格式1维护：显式使用等标签 (link) Varambally S, Dhanasekaran SM, Zhou M; et al. The polycomb group protein EZH2 is involved in progression of prostate cancer.. Nature. 2002, 419 (6907): 624–9. PMID 12374981. doi:10.1038/nature01075.  引文格式1维护：显式使用等标签 (link) Strausberg RL, Feingold EA, Grouse LH; et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.. Proc. Natl. Acad. Sci. U.S.A. 2003, 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.  引文格式1维护：显式使用等标签 (link) Scherer SW, Cheung J, MacDonald JR; et al. Human chromosome 7: DNA sequence and biology.. Science. 2003, 300 (5620): 767–72. PMC 2882961 . PMID 12690205. doi:10.1126/science.1083423.  引文格式1维护：显式使用等标签 (link) Hillier LW, Fulton RS, Fulton LA; et al. The DNA sequence of human chromosome 7.. Nature. 2003, 424 (6945): 157–64. PMID 12853948. doi:10.1038/nature01782.  引文格式1维护：显式使用等标签 (link) Kleer CG, Cao Q, Varambally S; et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells.. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (20): 11606–11. PMC 208805 . PMID 14500907. doi:10.1073/pnas.1933744100.  引文格式1维护：显式使用等标签 (link)