Up-regulated oxidized USP2a can increase Mdm2-p60-p53 to promote cell apoptosis

Hanqing Zhu; Hongliang Zhang; Jiahui Guo; Chao Zhang; Quanwu Zhang; Fenghou Gao

doi:10.1016/j.yexcr.2023.113597

Up-regulated oxidized USP2a can increase Mdm2-p60-p53 to promote cell apoptosis

Exp Cell Res. 2023 Jun 1;427(1):113597. doi: 10.1016/j.yexcr.2023.113597. Epub 2023 Apr 10.

Authors

Hanqing Zhu¹, Hongliang Zhang², Jiahui Guo³, Chao Zhang⁴, Quanwu Zhang⁵, Fenghou Gao⁶

Affiliations

¹ Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. Electronic address: zhuhanqing1123@163.com.
² Department of Blood Transfusion of Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, 450053, China. Electronic address: 1477494845@qq.com.
³ Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, China. Electronic address: 12211010040@fudan.edu.cn.
⁴ Department of Geriatrics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, China. Electronic address: 2953982857@qq.com.
⁵ Department of Pathology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, China. Electronic address: zxyyzqw@163.com.
⁶ Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, China; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, China. Electronic address: fenghougao@163.com.

PMID: 37044314
DOI: 10.1016/j.yexcr.2023.113597

Abstract

Mdm2 promotes the ubiquitination and degradation of p53, while Mdm2-p60 can bind to p53 and reduce the Mdm2-induced p53 ubiquitination to improve its stability. USP2a can deubiquitinate and stabilize Mdm2, whether USP2a can regulate Mdm2-p60 needs to be further confirmed and elucidated. We found that oxidative stress can up-regulate USP2a at the post-transcriptional level and induce USP2a to be oxidized by forming inter-subunit disulfide bonds. The oxidized USP2a is closely related with cell apoptosis. In apoptotic cells, oxidized USP2a has enhanced protein stability and further stabilizes Mdm2-p60 through deubiquitination, and the USP2a-Mdm2-p60-p53 axis plays a role in cell apoptosis. Altogether USP2a is oxygen sensitive, oxidized USP2a exerts apoptotic effects through the Mdm2-p60-p53 axis, which provides an experimental basis for regulating p53 apoptotic signaling by targeting USP2a.

Keywords: Apoptosis; Mdm2-p60; Oxidative stress; Oxidized; USP2a.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Endopeptidases* / genetics
Proto-Oncogene Proteins c-mdm2 / genetics
Proto-Oncogene Proteins c-mdm2 / metabolism
Tumor Suppressor Protein p53* / genetics
Tumor Suppressor Protein p53* / metabolism
Ubiquitination

Substances

Tumor Suppressor Protein p53
Endopeptidases
Proto-Oncogene Proteins c-mdm2