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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Wei Y,Chen YH,Li LY,Lang J,Yeh SP,Shi B,Yang CC,Yang JY,Lin CY,Lai CC,Hung MCdoi
10.1038/ncb2139subject
Has Abstractpub_date
2011-01-01 00:00:00pages
87-94issue
1eissn
1465-7392issn
1476-4679pii
ncb2139journal_volume
13pub_type
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