Nature cell biology, 2011-01, Vol.13 (1), p.87-94
2011
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- Autor(en) / Beteiligte
- Titel
- CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells
- Ist Teil von
- Nature cell biology, 2011-01, Vol.13 (1), p.87-94
- Ort / Verlag
- England
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1465-7392eISSN: 1476-4679DOI: 10.1038/ncb2139Titel-ID: cdi_crossref_primary_10_1038_ncb2139
- Format
- –
- Schlagworte
- 2-Aminopurine - analogs & derivatives, 2-Aminopurine - pharmacology, Carrier Proteins - genetics, Carrier Proteins - metabolism, CDC2 Protein Kinase - antagonists & inhibitors, CDC2 Protein Kinase - genetics, CDC2 Protein Kinase - metabolism, Cell Differentiation, Cell Line, Cell Line, Tumor, Cell Movement, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Enhancer of Zeste Homolog 2 Protein, HEK293 Cells, HeLa Cells, Histone-Lysine N-Methyltransferase - metabolism, Histones - metabolism, Humans, Immunoblotting, Lysine - metabolism, Mesenchymal Stem Cells - cytology, Mesenchymal Stem Cells - metabolism, Methylation, Neoplasm Proteins, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Osteoblasts - cytology, Osteoblasts - metabolism, Phosphorylation, Polycomb Repressive Complex 2, Protein Binding, Repressor Proteins - genetics, Repressor Proteins - metabolism, RNA Interference, Threonine - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism