Akt-mediated phsophorylationof EZH2 suppresses methylation of lysine 27 in histone H3
Akt-mediated phsophorylationof EZH2 suppresses methylation of lysine 27 in histone H3
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DOI：
10.1126/science.1118947
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发表时间：
2005-10-14
期刊：
影响因子：
56.9
通讯作者：
Hung, MC
中科院分区：
文献类型：
--
作者：
Cha, TL;Zhou, BHP;Hung, MC
Zeste增强子同源物2（EZH2）是一种甲基转移酶，其通过使组蛋白H3中的赖氨酸27三甲基化的能力在许多生物过程中发挥重要作用。在这里，我们发现Akt磷酸化EZH2的丝氨酸21和抑制其甲基转移酶的活性，通过阻碍EZH2结合组蛋白H3，这导致赖氨酸27三甲基化和沉默基因的去抑制的减少。我们的研究结果表明Akt通过EZH2的磷酸化调节甲基化活性，这可能有助于肿瘤的发生。
Enhancer of Zeste homolog 2 (EZH2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone H3. Here, we show that Akt phosphorylates EZH2 at serine 21 and suppresses its methyltransferase activity by impeding EZH2 binding to histone H3, which results in a decrease of lysine 27 trimethylation and derepression of silenced genes. Our results imply that Akt regulates the methylation activity, through phosphorylation of EZH2, which may contribute to oncogenesis.