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

Nature cell biology | Jan 21, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21131960

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.

Pubmed ID: 21131960 RIS Download

Mesh terms: 2-Aminopurine | CDC2 Protein Kinase | Carrier Proteins | Cell Differentiation | Cell Line | Cell Line, Tumor | Cell Movement | DNA-Binding Proteins | HEK293 Cells | HeLa Cells | Histone-Lysine N-Methyltransferase | Histones | Humans | Immunoblotting | Lysine | Mesenchymal Stromal Cells | Methylation | Nuclear Proteins | Osteoblasts | Phosphorylation | Polycomb Repressive Complex 2 | Protein Binding | RNA Interference | Repressor Proteins | Threonine | Transcription Factors

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Associated grants

  • Agency: NCI NIH HHS, Id: P01 CA099031
  • Agency: NCI NIH HHS, Id: R01 CA109311
  • Agency: NCI NIH HHS, Id: R01 CA109311
  • Agency: NCI NIH HHS, Id: R01 CA109311-08

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