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Publication : Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell death.

First Author  Xie Q Year  2012
Journal  EMBO Rep Volume  13
Issue  4 Pages  371-7
PubMed ID  22402663 Mgi Jnum  J:200481
Mgi Id  MGI:5508710 Doi  10.1038/embor.2012.25
Citation  Xie Q, et al. (2012) Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell death. EMBO Rep 13(4):371-7
abstractText  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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