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標題: CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells
作者: Wei, Y.K.
Chen, Y.H.
Li, L.Y.
Lang, J.Y.
Yeh, S.P.
Shi, B.
Yang, C.C.
Yang, J.Y.
Lin, C.Y.
Lai, C.C.
Hung, M.C.
關鍵字: cyclin-dependent kinases;developmental regulators;histone h3;polycomb;breast;cancer;proliferation;lysine-27;prostate;receptor
Project: Nature Cell Biology
期刊/報告no:: Nature Cell Biology, Volume 13, Issue 1, Page(s) 87-U211.
Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyses the trimethylation of histone H3 on Lys 27 (H3K27), which represses gene transcription. EZH2 enhances cancer-cell invasiveness and regulates stem cell differentiation. Here, we demonstrate that EZH2 can be phosphorylated at Thr 487 through activation of cyclin-dependent kinase 1 (CDK1). The phosphorylation of EZH2 at Thr 487 disrupted EZH2 binding with the other PRC2 components SUZ12 and EED, and thereby inhibited EZH2 methyltransferase activity, resulting in inhibition of cancer-cell invasion. In human mesenchymal stem cells, activation of CDK1 promoted mesenchymal stem cell differentiation into osteoblasts through phosphorylation of EZH2 at Thr 487. These findings define a signalling link between CDK1 and EZH2 that may have an important role in diverse biological processes, including cancer-cell invasion and osteogenic differentiation of mesenchymal stem cells.
ISSN: 1465-7392
DOI: 10.1038/ncb2139
Appears in Collections:分子生物學研究所

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