近日,，國際著名雜志EMBO reports在線刊登了中科院生物物理研究所袁增強研究組等的最新研究成果“Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell death”,，文章中,，研究者報道了轉錄因子FOXO3的一種新的翻譯后修飾—賴氨酸甲基化及其在在神經細胞凋亡過程中所起的作用,。

轉錄因子FOXO家族在氧化壓力介導的神經細胞凋亡過程中發(fā)揮著非常重要的作用,。當前已經發(fā)現(xiàn),，F(xiàn)OXO存在著磷酸化、乙?；⒎核鼗确g后修飾,，對其功能存在重要的調控作用,。本論文發(fā)現(xiàn)FOXO存在一種新的翻譯后修飾——賴氨酸甲基化。賴氨酸甲基轉移酶Set9可以甲基化FOXO3的270位賴氨酸,，抑制其DNA結合能力和轉錄活性,。賴氨酸甲基化修飾下調了FOXO3的下游促凋亡基因Bim的表達，從而抑制了神經細胞的凋亡,。

本研究首次發(fā)現(xiàn)FOXO3存在賴氨酸甲基化修飾,，并且闡明了這種修飾抑制了其介導的神經細胞凋亡,。

本論文由生物物理所袁增強研究組,、北京生命科學院董夢秋研究組以及廈門大學尤涵研究組合作完成。生物物理所袁增強研究員為本文的通訊作者,，士研究生謝琦博,、郝玉民為本文共同第一作者。（生物谷Bioon.com）

doi:10.1038/embor.2012.25
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Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell death

Qi Xie1,2,*, Yumin Hao1,2,*, Li Tao3, Shengyi Peng1,2, Chitong Rao4, Hong Chen1, Han You5, Meng-qiu Dong3 & Zengqiang Yuan1

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.