Journal
EMBO REPORTS
Volume 13, Issue 4, Pages 371-377Publisher
WILEY
DOI: 10.1038/embor.2012.25
Keywords
apoptosis; FOXO3; methylation; signal transduction
Categories
Funding
- National Science Foundation of China [30870792, 81030025, 81125010]
- Ministry of Science and Technology of China [973-2009CB918704, 2012CB910701]
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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.
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