title: Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Tai-Lung
authors.initials: TL
authors.lastname: Cha
authors.forename: Binhua P
authors.initials: BP
authors.lastname: Zhou
authors.forename: Weiya
authors.initials: W
authors.lastname: Xia
authors.forename: Yadi
authors.initials: Y
authors.lastname: Wu
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Yang
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Ping
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002522:Chlorocebus aethiops; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation; D063151:Polycomb Repressive Complex 2; D011485:Protein Binding; D011496:Protein Methyltransferases; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D002867:Chromones; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D018398:Homeodomain Proteins; D009025:Morpholines; D011506:Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C097899:homeobox protein HOXA9; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D012694:Serine; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D008239:Lysine