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PMID: 20935635 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Nature cell biology ·Vol. 12 ·No. 11 ·2010-11-00 ·Pages 1108-14

Chen S, Bohrer LR, Rai AN, Pan Y, Gan L, Zhou X, Bagchi A, Simon JA, Huang H

Abstract

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. This function of EZH2 is important for cell proliferation and inhibition of cell differentiation, and is implicated in cancer progression. 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.

MeSH Terms
CDC2 Protein Kinase/genetics,metabolism Cyclin-Dependent Kinase 2/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Enhancer of Zeste Homolog 2 Protein Epigenesis, Genetic/genetics Gene Silencing HEK293 Cells Humans Phosphorylation Polycomb Repressive Complex 2 Transcription Factors/genetics,metabolism Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins Transcription Factors EZH2 protein, human Enhancer of Zeste Homolog 2 Protein Polycomb Repressive Complex 2 CDC2 Protein Kinase CDK2 protein, human Cyclin-Dependent Kinase 2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chen Shuai
Masonic Cancer Center, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Bohrer Laura R
Rai Aswathy N
Pan Yunqian
Gan Lu
Zhou Xianzheng
Bagchi Anindya
Simon Jeffrey A
Huang Haojie
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2116
Published
2010-11-00
Epub
2010-00-10
Pages
1108-14
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3292434
Subset
IM
Grants
NIGMS NIH HHS · R01 GM049850 · United States
NIGMS NIH HHS · GM49850 · United States
NCI NIH HHS · CA130908 · United States
NCI NIH HHS · R01 CA130908-02 · United States
NCI NIH HHS · R01 CA134514-02 · United States
NCI NIH HHS · CA134514 · United States
NCI NIH HHS · R01 CA130908 · United States
NCI NIH HHS · R01 CA134514 · United States
External Links
PubMed source DOI: 10.1038/ncb2116 PMC Full Text View journal details
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