Repression of p53 function by SIRT5-mediated desuccinylation at Lysine 120 in response to DNA damage

被引：41

作者：

Liu, Xing ^{[1
,2
]}

Rong, Fangjing ^{[1
,2
]}

Tang, Jinhua ^{[1
,2
]}

Zhu, Chunchun ^{[1
,2
]}

Chen, Xiaoyun ^{[1
,2
]}

Jia, Shuke ^{[1
,2
]}

Wang, Zixuan ^{[1
,2
]}

Sun, Xueyi ^{[1
,2
]}

Deng, Hongyan ^{[3
]}

Zha, Huangyuan ^{[1
]}

Ouyang, Gang ^{[1
]}

Xiao, Wuhan ^{[1
,2
,4
,5
,6
]}

机构：

[1] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

[4] Chinese Acad Sci, Innovat Acad Seed Design, Wuhan, Peoples R China

[5] Hubei Hongshan Lab, Wuhan 430070, Peoples R China

[6] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China

来源：

CELL DEATH AND DIFFERENTIATION | 2022年 / 29卷 / 04期

基金：

中国国家自然科学基金;

关键词：

CELL-CYCLE ARREST; MUTANT P53; SUCCINYLATION; ACETYLATION; ACTIVATION; CANCER; SIRT5; APOPTOSIS; IDENTIFICATION; MALONYLATION;

D O I：

10.1038/s41418-021-00886-w

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

p53 is a classic tumor suppressor that functions in maintaining genome stability by inducing either cell arrest for damage repair or cell apoptosis to eliminate damaged cells in response to different types of stress. Posttranslational modifications (PTMs) of p53 are thought to be the most effective way for modulating of p53 activation. Here, we show that SIRT5 interacts with p53 and suppresses its transcriptional activity. Using mass spectrometric analysis, we identify a previously unknown PTM of p53, namely, succinylation of p53 at Lysine 120 (K120). SIRT5 mediates desuccinylation of p53 at K120, resulting in the suppression of p53 activation. Moreover, using double knockout mice (p53(-/-)Sirt5(-/-)), we validate that the suppression of p53 target gene expression and cell apoptosis upon DNA damage is dependent on cellular p53. Our study identifies a novel PTM of p53 that regulates its activation as well as reveals a new target of SIRT5 acting as a desuccinylase.

引用

页码：722 / 736

页数：15

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