Targeting EZH2 for cancer therapy: progress and perspective.
Targeting EZH2 for cancer therapy: progress and perspective.
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以 EZH2 为靶点的癌症治疗：进展与展望
DOI：
10.2174/1389203716666150409100233
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发表时间：
2015
影响因子：
2.8
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Han Li C;Chen Y
Zeste增强子同源物2（Enhancer of Zeste Homolog 2，EZH 2）是多梳抑制复合物2（polycomb repressive complex 2，PRC 2）的核心组分，具有在组蛋白H3中产生二/三甲基化赖氨酸27的酶活性。EZH 2在早期发育过程中具有重要作用，其失调与各种组织类型中的肿瘤发生密切相关。越来越多的证据表明，通过靶向癌细胞中的EZH 2具有显著的治疗潜力。第一部分回顾了目前针对癌症中EZH 2的策略，并评估了用于破坏EZH 2功能的可用化合物和药物。然后，我们提供了对不同癌症类型中靶向EZH 2研究的未来方向的见解。我们全面讨论了目前对EZH 2的结构和生物活性的理解，2）它在PRC 2组装和其他蛋白组分的募集中的作用，3）指导EZH 2靶向基因组区域的分子事件，以及4）EZH 2蛋白的翻译后修饰。该讨论为激发开发新策略以消除癌细胞中EZH 2相关效应提供了基础。
Enhancer of Zeste Homolog 2 (EZH2) is the core component of the polycomb repressive complex 2 (PRC2), possessing the enzymatic activity in generating di/tri-methylated lysine 27 in histone H3. EZH2 has important roles during early development, and its dysregulation is heavily linked to oncogenesis in various tissue types. Accumulating evidences suggest a remarkable therapeutic potential by targeting EZH2 in cancer cells. The first part reviews current strategies to target EZH2 in cancers, and evaluates the available compounds and agents used to disrupt EZH2 functions. Then we provide insight to the future direction of the research on targeting EZH2 in different cancer types. We comprehensively discuss the current understandings of the 1) structure and biological activity of EZH2, 2) its role during the assembling of PRC2 and recruitment of other protein components, 3) the molecular events directing EZH2 to target genomic regions, and 4) post-translational modification at EZH2 protein. The discussion provides the basis to inspire the development of novel strategies to abolish EZH2-related effects in cancer cells.