SIRT3 differentially regulates lysine benzoylation from SIRT2 in mammalian cells

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2024-10-16 DOI:10.1016/j.isci.2024.111176

Panpan Peng , Ying Lu , Xuelian Ren , Cong Yan , Xinlong Guo , Ruilong Liu , Xiaohan Song , He Huang

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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.

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SIRT3 对哺乳动物细胞中 SIRT2 的赖氨酸苯甲酰化具有不同的调节作用

赖氨酸苯甲酰化（Kbz）是我们发现的一种新型蛋白质翻译后修饰（PTM），引起了广泛关注。虽然我们最初发现 SIRT2 是哺乳动物细胞中的脱苯甲酰化酶，但最近的研究结果表明其排他性可能受到质疑。然而，哺乳动物细胞中的其他脱苯甲酰化酶仍未得到充分探索。在这里，我们的研究揭示了 SIRT3 是另一种脱苯甲酰基酶。通过定量分析，我们在哺乳动物细胞中发现了 1,075 个 Kbz 位点，其中 44 个由 SIRT3 特异性介导，66 个受 SIRT2 影响。值得注意的是，SIRT3 和 SIRT2 调节不同的 Kbz 底物，表明它们参与了不同的细胞过程。功能研究表明，SIRT3 可调控苯甲酰基化蛋白肽基脯氨酰顺反异构酶 F（PPIF），其中 K73bz 和 K197bz 明显减少了与肿瘤抑制因子 p53 的相互作用。此外，ATP-柠檬酸酶（ACLY）上的 K978bz 显著抑制了其酶活性。这项研究不仅发现了一种去苯甲酰化酶及其 Kbz 底物，还增进了我们对 Kbz 生物功能的了解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.