title: Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell death.
abstract: FOXO transcription factors have a critical role in oxidative stress-induced neuronal cell death. A variety of post-translational modifications of FOXO family proteins have been reported, including phosphorylation, acetylation, ubiqutination and recently arginine methylation. Here, we demonstrate that the methyltransferase Set9 methylates FOXO3 at lysine 270. Methylation of FOXO3 leads to the inhibition of its DNA-binding activity and transactivation. Accordingly, lysine methylation reduces oxidative stress-induced and FOXO3-mediated Bim expression and neuronal apoptosis in neurons. Collectively, these findings define a novel modification of FOXO3 and show that lysine methylation negatively regulates FOXO3-mediated transcription and neuronal apoptosis.
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.forename: Yumin
authors.initials: Y
authors.lastname: Hao
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Shengyi
authors.initials: S
authors.lastname: Peng
authors.forename: Chitong
authors.initials: C
authors.lastname: Rao
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Han
authors.initials: H
authors.lastname: You
authors.forename: Meng-qiu
authors.initials: MQ
authors.lastname: Dong
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D004247:DNA / Q000378:metabolism; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; D008239:Lysine