EZH2

位於7號人類染色體的基因

組蛋白-離氨酸N-甲基轉移酶EZH2是一個由人類EZH2基因所編碼的[1][2]。已鑑定該基因轉錄出的兩種轉錄物變異體編碼不同的亞型[3]

zeste同源物2增強子(果蠅屬)
有效結構
PDB 直系同源檢索:PDBe, RCSB
標識
代號 EZH2; ENX-1; ENX1; EZH1; KMT6; KMT6A; WVS2
擴展標識 遺傳學601573 鼠基因107940 同源基因37926 GeneCards: EZH2 Gene
EC編號 2.1.1.43
RNA表達模式
更多表達數據
直系同源體
物種 人類 小鼠
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查詢 [1] [2]

功能

編輯

該基因編碼的蛋白屬於多梳家族(PcG)成員。PcG家族成員相互結合形成多聚蛋白複合物,這種複合物涉及到在細胞世代間維持基因的轉錄抑制狀態。EZH2主要通過將三個甲基基團加到組蛋白3的27號賴氨酸(H3K27)上行使基因沉默者的角色,三甲基化H3K27是維持染色質凝聚的一種重要修飾[4]

該蛋白與胚胎外胚層發育蛋白(EED)、癌蛋白VAV1和X連鎖核蛋白(XNP)之間關係密切。EZH2蛋白可能在造血系統和中樞神經系統中起到重要作用[3]

臨床意義

編輯

EZH2基因中的突變導致韋弗綜合症[5]miR-101在正常情況下阻止編碼EZH2的mRNA進入翻譯階段。因此這一微RNA的基因一旦缺失就會導致產生過量的EZH2[6]。EZH2過多表達可能導致癌症形成,這是因為過多地組蛋白甲基化抑癌基因將導致其表達沉默。一種靶向EZH2藥物的臨床前模型顯示其能夠抑制腦癌及前列腺癌的進展[7][8]

相互作用

編輯

EZH2與下列蛋白質有着蛋白質交互作用ATRX[9]EED[10][11]HDAC1[12]HDAC2引用錯誤:<ref>標籤有衝突或無效的屬性VAV1[13]

參考文獻

編輯
  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. PMID 8954776. doi:10.1006/geno.1996.0588. 
  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. PMID 17172412. doi:10.1158/1535-7163.MCT-06-0418. 
  3. ^ 3.0 3.1 Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila). (原始內容存檔於2019-10-16). 
  4. ^ 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. 
  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. PMID 22177091. doi:10.1016/j.ajhg.2011.11.018. 
  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. PMID 19934320. doi:10.1158/0008-5472.CAN-09-1622. 
  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. PMC 3100246 . PMID 21501485. doi:10.1186/1476-4598-10-40. 
  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. PMID 9499421. doi:10.1093/hmg/7.4.679. 
  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. ^ 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. 
  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. 

深入閱讀

編輯