State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
EMBO Rep. 2012 Apr;13(4):371-7. doi: 10.1038/embor.2012.25.
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.
FOXO 转录因子在氧化应激诱导的神经元细胞死亡中具有关键作用。已经报道了 FOXO 家族蛋白的多种翻译后修饰，包括磷酸化、乙酰化、泛素化和最近的精氨酸甲基化。在这里，我们证明了甲基转移酶 Set9 在赖氨酸 270 处甲基化 FOXO3。FOXO3 的甲基化导致其 DNA 结合活性和转录激活的抑制。因此，赖氨酸甲基化减少了氧化应激诱导的和 FOXO3 介导的 Bim 表达和神经元凋亡。总的来说，这些发现定义了 FOXO3 的一种新的修饰方式，并表明赖氨酸甲基化负调控 FOXO3 介导的转录和神经元凋亡。
