P53 Suppresses SENP3 Phosphorylation to Mediate G2 Checkpoint

Overview

Journal Cell Discov

Date 2020 May 1

PMID 32351703

Citations 9

Authors

Yang Wang

Jing Tian

Chao Huang

Jiao Ma

Gaolei Hu

Yalan Chen

Tianshi Wang

Rong Cai

Yong Zuo

Hongsheng Tan

Qiuju Fan

Baijun Dong

Wei Xue

Jing Yi

Guoqiang Chen

Jun Tu

Jinke Cheng

Affiliations

Soon will be listed here.

Abstract

In response to DNA damage, p53-mediated signaling is regulated by protein phosphorylation and ubiquitination to precisely control G2 checkpoint. Here we demonstrated that protein SUMOylation also engaged in regulation of p53-mediated G2 checkpoint. We found that G2 DNA damage suppressed SENP3 phosphorylation at G2/M phases in p53-dependent manner. We further found that the suppression of SENP3 phosphorylation was crucial for efficient DNA damage/p53-induced G2 checkpoint and G2 arrest. Mechanistically, we identified Cdh1, a subunit of APC/C complex, was a SUMOylated protein at G2/M phase. SENP3 could de-SUMOylate Cdh1. DNA damage/p53-induced suppression of SENP3 phosphorylation activated SENP3 de-SUMOylation of Cdh. De-SUMOylation promoted Cdh1 de-phosphorylation by phosphatase Cdc14B, and then activated APC/C E3 ligase activity to ubiquitate and degrade Polo-like kinase 1 (Plk1) in process of G2 checkpoint. These data reveal that p53-mediated inhibition of SENP3 phosphorylation regulates the activation of Cdc14b-APC/C-Plk1 axis to control DNA damage-induced G2 checkpoint.

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