EZH2

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zeste同源物2增强子(果蝇属)
有效结构
PDB 直系同源检索:PDBe, RCSB
标识
代号 EZH2; ENX-1; ENX1; EZH1; KMT6; KMT6A; WVS2
扩展标识 遗传学601573 鼠基因107940 同源基因37926 GeneCards: EZH2 Gene
EC編號 2.1.1.43
RNA表达模式
PBB GE EZH2 203358 s at tn.png
更多表达数据
直系同源体
物种 人类 鼠类
Entrez 2146 14056
Ensembl ENSG00000106462 ENSMUSG00000029687
UniProt Q15910 Q61188
mRNA序列 NM_001203247 NM_001146689
蛋白序列 NP_001190176 NP_001140161
基因位置 Chr 7:
148.5 – 148.58 Mb
Chr 6:
47.53 – 47.6 Mb
PubMed查询 [1] [2]

组蛋白-赖氨酸N-甲基转移酶EZH2是一个由人类EZH2基因所编码的[1][2]。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[3]

功能[编辑]

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[4]

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[3]

临床意义[编辑]

EZH2基因中的突变导致韦弗综合征[5]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[6]。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[7][8]

相互作用[编辑]

EZH2与下列蛋白质有着蛋白質交互作用ATRX[9]EED[10][11]HDAC1[12]HDAC2[12]VAV1[13]

参考文献[编辑]

  1. ^ 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. doi:10.1006/geno.1996.0588. PMID 8954776. 
  2. ^ 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. doi:10.1158/1535-7163.MCT-06-0418. PMID 17172412. 
  3. ^ 3.0 3.1 Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila). 
  4. ^ Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. NOV 2002, 298 (5595): 1039–43. doi:10.1126/science.1076997. PMID 12351676. 
  5. ^ 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. doi:10.1016/j.ajhg.2011.11.018. PMID 22177091. 
  6. ^ 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. 
  7. ^ 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. doi:10.1158/0008-5472.CAN-09-1622. PMID 19934320. 
  8. ^ 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. doi:10.1186/1476-4598-10-40. PMC 3100246. PMID 21501485. 
  9. ^ 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. doi:10.1093/hmg/7.4.679. PMID 9499421. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 12.0 12.1 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. doi:10.1038/70602. PMID 10581039. 
  13. ^ 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. 

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