CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells.
Journal:
Nat. Cell Biol. 2011 JanAuthors:
Wei Y, Chen YH, Li LY, Lang J, Yeh SP, Shi B, Yang CC, Yang JY, Lin CY, Lai CC, Hung MC
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 SUZ
...[more]12 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.[less]
Mesh Headings:
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