Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3.
Enhancer of Zeste homolog 2 (EZH2) is a methyltransferase that plays an important role in many biological processes through its ability to trimethylate lysine 27 in histone H3. Here, we show that Akt phosphorylates EZH2 at serine 21 and suppresses its methyltransferase activity by impeding EZH2 binding to histone H3, ... which results in a decrease of lysine 27 trimethylation and derepression of silenced genes. Our results imply that Akt regulates the methylation activity, through phosphorylation of EZH2, which may contribute to oncogenesis.
Mesh Terms:
3T3 Cells, Animals, COS Cells, Cell Line, Cell Transformation, Neoplastic, Cercopithecus aethiops, Chromones, DNA-Binding Proteins, Enzyme Inhibitors, Gene Expression Regulation, Hela Cells, Histone-Lysine N-Methyltransferase, Histones, Homeodomain Proteins, Humans, Lysine, Methylation, Mice, Molecular Sequence Data, Morpholines, Phosphorylation, Protein Binding, Protein Methyltransferases, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Serine, Transcription Factors
3T3 Cells, Animals, COS Cells, Cell Line, Cell Transformation, Neoplastic, Cercopithecus aethiops, Chromones, DNA-Binding Proteins, Enzyme Inhibitors, Gene Expression Regulation, Hela Cells, Histone-Lysine N-Methyltransferase, Histones, Homeodomain Proteins, Humans, Lysine, Methylation, Mice, Molecular Sequence Data, Morpholines, Phosphorylation, Protein Binding, Protein Methyltransferases, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Serine, Transcription Factors
Science
Date: Oct. 14, 2005
PubMed ID: 16224021
View in: Pubmed Google Scholar
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