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- Title
CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells.
- Authors
Yongkun Wei; Ya-Huey Chen; Long-Yuan Li; Jingyu Lang; Su-Peng Yeh; Bin Shi; Cheng-Chieh Yang; Jer-Yen Yang; Chun-Yi Lin; Chien-Chen Lai; Mien-Chie Hung
- Abstract
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.
- Publication
Nature Cell Biology, 2011, Vol 13, Issue 1, p87
- ISSN
1465-7392
- Publication type
Academic Journal
- DOI
10.1038/ncb2139