| Literature DB >> 34642466 |
Xing Liu1,2, Fangjing Rong1,2, Jinhua Tang1,2, Chunchun Zhu1,2, Xiaoyun Chen1,2, Shuke Jia1,2, Zixuan Wang1,2, Xueyi Sun1,2, Hongyan Deng3, Huangyuan Zha1, Gang Ouyang1, Wuhan Xiao4,5,6,7,8.
Abstract
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.Entities:
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Year: 2021 PMID： 34642466 PMCID： PMC8989948 DOI： 10.1038/s41418-021-00886-w
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 12.067