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Lysine methylation of FOXO3 regulates oxidative stress‐induced neuronal cell death
Author(s) -
Xie Qi,
Hao Yumin,
Tao Li,
Peng Shengyi,
Rao Chitong,
Chen Hong,
You Han,
Dong Mengqiu,
Yuan Zengqiang
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.25
Subject(s) - transactivation , foxo3 , methylation , oxidative stress , microbiology and biotechnology , transcription factor , acetylation , biology , lysine , dna methylation , programmed cell death , apoptosis , phosphorylation , gene expression , biochemistry , dna , protein kinase b , gene , amino acid
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.