新研究：哺乳動物細胞中SIRT3對賴氨酸苯甲酰化的調節存在差異

2024年10月，中國科學院大學杭州高等研究院藥學院；中國科學院上海藥物研究所化學生物學國家重點實驗室；南京中醫藥大學中藥學院 (School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China ；State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China；School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China) He Huang老師研究團隊在《iScience.》上發表論文：

“SIRT3 differentially regulates lysine benzoylation from SIRT2 in mammalian cells"

“哺乳動物細胞中SIRT3對賴氨酸苯甲酰化的調節存在差異"

Abstract：

Lysine benzoylation (Kbz), a new type of protein post-translational modification (PTM) we discovered, has garnered significant attention.  While we initially identified SIRT2 as a debenzoylase in mammalian cells, recent findings suggest its exclusivity may be questioned.  However, other debenzoylases in mammalian cells remain underexplored.  Here, our study reveals SIRT3 as an additional debenzoylase.  Through quantitative analysis, we identified 1,075 Kbz sites in mammalian cells, with 44 specifically mediated by SIRT3 and 66 influenced by SIRT2.  Notably, SIRT3 and SIRT2 regulate distinct Kbz substrates, indicating involvement in different cellular processes.  Functional investigations demonstrated SIRT3's regulation of benzoylated protein peptidyl-prolyl cis-trans isomerase F (PPIF), where K73bz and K197bz markedly diminished interactions with the tumor suppressor p53.  Additionally, K978bz on ATP-citrate lyase (ACLY) notably inhibited its enzymatic activity.  This study not only identifies a debenzoylase and its Kbz substrates but also enhances our understanding of Kbz's biological functions.

摘要：

賴氨酸苯甲酰化（Kbz）是我們發現的一種新的蛋白質翻譯后修飾（PTM），引起了人們的廣泛關注。雖然我們最初在哺乳動物細胞中確定SIRT2是一種脫苯甲酰酶，但最近的研究結果表明，它的專一性可能受到質疑。然而，哺乳動物細胞中的其他脫苯甲酰酶仍未得到充分研究。在這里，我們的研究表明SIRT3是另一種脫苯甲酰酶。通過定量分析，我們在哺乳動物細胞中確定了1,075個Kbz位點，其中44個是SIRT3特異性介導的，66個是受SIRT2影響的。值得注意的是，SIRT3和SIRT2調節不同的Kbz底物，表明參與不同的細胞過程。功能研究表明SIRT3調節苯甲酰化蛋白肽酰脯氨酸順式反式異構酶F (PPIF)，其中K73bz和K197bz顯著降低了與腫瘤抑制因子p53的相互作用。此外，K978bz對atp -檸檬酸裂解酶（ACLY）的酶活性有明顯的抑制作用。本研究不僅鑒定了一種脫苯甲酰酶及其Kbz底物，而且提高了我們對Kbz生物學功能的認識。

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