EZH2组蛋白甲基转移酶在肿瘤发生发展中的作用

Roles of EZH2 Histone Methyltransferase in Tumorigenesis

PcG(Polycomb group)蛋白家族是一组在胚胎发育中起作用的基因调控因子,根据其功能不同分为两种蛋白质复合物,即PRC1和PRC2。PRC2是一个作用于组蛋白H3赖氨酸位点K27的高度保守的组蛋白甲基转移酶,EZH2是构成PRC2蛋白复合物的一个催化亚基。大部分肿瘤研究表明,EZH2过表达于多种癌组织,如前列腺癌和乳腺癌。虽然目前关于EZH2在肿瘤发展中的作用机制还不明确,但是EZH2介导的组蛋白甲基化与DNA甲基化间的功能联系提示两者所致的基因沉默机制在肿瘤抑制因子的缺失中起作用。阐述EZH2的基本分子生物功能及其与多种不同肿瘤组织之间的密切关系,讨论EZH2与其他表观遗传修饰酶间的关系以及EZH2过表达的结果及其在肿瘤形成中的作用。

The Polycomb group（PcG）protein family is a group of gene regulatory elements playing roles in embryonic development,which functioning in tow distinct protein complexes termed Polycomb-repressive complex 1（PRC1） and Polycomb-repressive complex 2（PRC2）. EZH2 is the catalytic subunit of PRC2,which is a highly conserved histone methyltransferase that targets lysine-27 of histone H3. Most studies on human tumors show that EZH2 is over-expression in a variety of tumors,including prostate and breast. Although the mechanism of EZH2 with cancer progression is not determined,functional link between EZH2-mediated histone methylation and DNA methylation indicate which involved in the gene silencing machinery implicated in tumor suppressor loss. The authors review the basic molecular biology of EZH2 and the findings of EZH2 in different cancers. And also discuss EZH2 connections to other epigenetic modifying enzymes,as well as the consequences of EZH2 overabundance and its potential roles in tumorigenesis.