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The phosphorylation-deubiquitination positive feedback loop of the CHK2-USP7 axis stabilizes p53 under oxidative stress

Authors :
Jingwei Liu
Liangzi Cao
Yubang Wang
Yu Zou
Qiqiang Guo
Shu Chen
Bo Jiang
Xuan Wu
Lixia Zheng
Siyi Zhang
Songming Lu
Keshen Zhou
Pengcheng Jiang
Yutong Xiao
Ruohan Yang
Shiyuan Dong
Ziwei Li
Di Chen
Ying Zhang
Naijin Zhang
Guozhe Sun
Chengzhong Xing
Xiaoyu Song
Zhenning Wang
Liu Cao
Source :
Cell Reports, Vol 43, Iss 6, Pp 114366- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear. Here, we propose that DNA damage induces reactive oxygen species (ROS) production and activates ATM-CHK2, and CHK2 then phosphorylates USP7 at S168 and T231. USP7 phosphorylation is essential for its deubiquitination activity toward p53. USP7 also deubiquitinates CHK2 at K119 and K131, increasing CHK2 stability and creating a positive feedback loop between CHK2 and USP7. Compared to peri-tumor tissues, thyroid cancer and colon cancer tissues show higher CHK2 and phosphorylated USP7 (S168, T231) levels, and these levels are positively correlated. Collectively, our results uncover a phosphorylation-deubiquitination positive feedback loop involving the CHK2-USP7 axis that supports the stabilization of p53 and the maintenance of cell homeostasis.

Details

Language :
English
ISSN :
22111247
Volume :
43
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.065b697ade3469dbcfa880c2b16d7fd
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2024.114366