新研究：哺乳動(dòng)物細(xì)胞中SIRT3對(duì)賴氨酸苯甲酰化的調(diào)節(jié)存在差異

2024年10月，中國(guó)科學(xué)院大學(xué)杭州高等研究院藥學(xué)院；中國(guó)科學(xué)院上海藥物研究所化學(xué)生物學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室；南京中醫(yī)藥大學(xué)中藥學(xué)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(tuán)隊(duì)在《iScience.》上發(fā)表論文：

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

“哺乳動(dòng)物細(xì)胞中SIRT3對(duì)賴氨酸苯甲酰化的調(diào)節(jié)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(fā)現(xiàn)的一種新的蛋白質(zhì)翻譯后修飾（PTM），引起了人們的廣泛關(guān)注。雖然我們最初在哺乳動(dòng)物細(xì)胞中確定SIRT2是一種脫苯甲酰酶，但最近的研究結(jié)果表明，它的專一性可能受到質(zhì)疑。然而，哺乳動(dòng)物細(xì)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?cè)诓溉閯?dòng)物細(xì)胞中確定了1,075個(gè)Kbz位點(diǎn)，其中44個(gè)是SIRT3特異性介導(dǎo)的，66個(gè)是受SIRT2影響的。值得注意的是，SIRT3和SIRT2調(diào)節(jié)不同的Kbz底物，表明參與不同的細(xì)胞過程。功能研究表明SIRT3調(diào)節(jié)苯甲酰化蛋白肽酰脯氨酸順式反式異構(gòu)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(duì)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(duì)Kbz生物學(xué)功能的認(rèn)識(shí)。

該論文中，293T和HepG2細(xì)胞的體外培養(yǎng)是使用Ausbian特級(jí)胎牛血清完成的。