CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells

• Published in: Nature cell biology Vol. 13; no. 1; pp. 87 - 94
• Main Authors: Li, Long-Yuan, Hung, Mien-Chie, Wei, Yongkun, Chen, Ya-Huey, Lang, Jingyu, Yeh, Su-Peng, Shi, Bin, Yang, Cheng-Chieh, Yang, Jer-Yen, Lin, Chun-Yi, Lai, Chien-Chen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2011; Nature Publishing Group
• Subjects: 2-Aminopurine - analogs & derivatives; 2-Aminopurine - pharmacology; 631/136/1660; 631/80/458/1648; 631/80/458/1733; 631/80/86; Antibodies; Biology; Biomedical and Life Sciences; Cancer; Cancer Research; Carrier Proteins - genetics; Carrier Proteins - metabolism; Catalysis; CDC2 Protein Kinase - antagonists & inhibitors; CDC2 Protein Kinase - genetics; CDC2 Protein Kinase - metabolism; Cell Biology; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cyclin-dependent kinases; Developmental Biology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enhancer of Zeste Homolog 2 Protein; Gene expression; HEK293 Cells; HeLa Cells; Histone-Lysine N-Methyltransferase - metabolism; Histones - metabolism; Humans; Immunoblotting; Invasiveness; Kinases; letter; Life Sciences; Lysine - metabolism; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Methylation; Neoplasm Proteins; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncology; Osteoblasts - cytology; Osteoblasts - metabolism; Phosphorylation; Physiological aspects; Polycomb Repressive Complex 2; Protein Binding; Protein kinases; Proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA Interference; Stem Cells; Threonine - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; United States; Taiwan; United States > US; China
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb2139

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.