...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation
【24h】

Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation

机译：小分子抑制剂对Ezh2的选择性抑制可阻止肿瘤细胞增殖

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component of the Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 were identified in diffused large B-cell lymphomas and follicular lymphomas. To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor. Ell, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine. El 1-treated cells exhibit genome-wide loss of H3K27 methylation and activation of PRC2 target genes. Furthermore, inhibition of Ezh2 by EI1 in diffused large B-cell lymphomas cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest, and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer.
机译：Ezh2（zeste同源物2的增强剂）蛋白是Polycomb阻抑复合物2（PRC2）的酶成分，它通过使组蛋白H3（H3K27）的赖氨酸27甲基化来抑制基因表达，并在胚胎发育过程中调节细胞增殖和分化。最近，在弥漫性大B细胞淋巴瘤和滤泡性淋巴瘤中发现了Ezh2的热点突变。为了研究肿瘤的生长是否依赖于Ezh2的酶促活性，我们开发了一种有效的选择性小分子抑制剂。 Ell通过直接与酶结合并与甲基供体S-腺苷甲硫氨酸竞争而抑制Ezh2的酶活性。 El 1处理的细胞表现出全基因组H3K27甲基化的丧失和PRC2目标基因的激活。此外，在携带Y641突变的弥漫性大B细胞淋巴瘤细胞中，EI1对Ezh2的抑制作用导致增殖减少，细胞周期停滞和凋亡。这些结果提供了强有力的验证，证明Ezh2是治疗癌症的潜在治疗靶标。

著录项

  • 来源
  • 作者

    Wei Qi; HoMan Chan; Lin Teng; Ling Li; Shannon Chuai; Ruipeng Zhang; Jue Zeng; Min Li; Hong Fan; Ying Lin; Justin Gu; Ophelia Ardayfio; Ji-Hu Zhang; Xiaoxia Yan; Jialuo Fang; Yuan Mi; Man Zhang; Tao Zhou; Grace Feng; Zijun Chen; Guobin Li; Teddy Yang; Kehao Zhao; Xianghui Liu; Zhengtian Yu; Chris X. Lu; Peter Atadja; En Li;

  • 作者单位

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China,Oncology, Novartis Institutes for BioMedical Research, Cambridge,MA 02739;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    Center for Proteomic Chemistry, Novartis Institutes for BioMedical Research, Cambridge, MA 02139;

    Center for Proteomic Chemistry, Novartis Institutes for BioMedical Research, Cambridge, MA 02139;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

    China Novartis Institutes for BioMedical Research, Shanghai 201203, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号