Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2

被引：211

作者：

Chen, Shuai ^{[1
,2
]}

Bohrer, Laura R. ^{[1
,2
]}

Rai, Aswathy N. ^{[1
,3
]}

Pan, Yunqian ^{[1
,2
]}

Gan, Lu ^{[1
,2
]}

Zhou, Xianzheng ^{[1
,4
]}

Bagchi, Anindya ^{[1
,5
]}

Simon, Jeffrey A. ^{[1
,3
,5
]}

Huang, Haojie ^{[1
,2
]}

机构：

[1] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[3] Univ Minnesota, Biochem Mol Biol & Biophys Grad Program, Minneapolis, MN 55455 USA

[4] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA

[5] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA

来源：

NATURE CELL BIOLOGY | 2010年 / 12卷 / 11期

基金：

美国国家卫生研究院;

关键词：

HISTONE METHYLTRANSFERASE ACTIVITY; H3; LYSINE-27; METHYLATION; DEVELOPMENTAL REGULATORS; POLYCOMB; EXPRESSION; CANCER; COMPLEXES; DIFFERENTIATION; PROLIFERATION; MECHANISMS;

D O I：

10.1038/ncb2116

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), has an essential role in promoting histone H3 lysine 27 trimethylation (H3K27me3) and epigenetic gene silencing(1-4). This function of EZH2 is important for cell proliferation and inhibition of cell differentiation, and is implicated in cancer progression(5-10). Here, we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif. Phosphorylation of Thr 350 is important for recruitment of EZH2 and maintenance of H3K27me3 levels at EZH2-target loci. Blockage of Thr 350 phosphorylation not only diminishes the global effect of EZH2 on gene silencing, it also mitigates EZH2-mediated cell proliferation and migration. These results demonstrate that CDK-mediated phosphorylation is a key mechanism governing EZH2 function and that there is a link between the cell-cycle machinery and epigenetic gene silencing.

引用

页码：1108 / U118

页数：19

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