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

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

Authors

  • Wei Y
  • Chen YH
  • Li LY
  • Lang J
  • Yeh SP
  • Shi B
  • Yang CC
  • Yang JY
  • Lin CY
  • Lai CC
  • Hung MC

Journal

Nature cell biology

Publication Data

January 21, 2011

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

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