P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint

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

doi:10.1038/s41421-020-0154-2

P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint

Cell Discov. 2020 Apr 21:6:21. doi: 10.1038/s41421-020-0154-2. eCollection 2020.

Authors

Yang Wang^{1

2

3}, Jing Tian^{1

2

3}, Chao Huang⁴, Jiao Ma^{1

2

3}, Gaolei Hu^{1

2

3}, Yalan Chen^{1

2

3}, Tianshi Wang^{1

2

3}, Rong Cai^{1

2

3}, Yong Zuo^{1

2

3}, Hongsheng Tan⁵, Qiuju Fan^{1

2

3}, Baijun Dong^{1

3}, Wei Xue^{1

3}, Jing Yi^{1

2

3}, Guoqiang Chen², Jun Tu^{1

2

3}, Jinke Cheng^{1

2

3}

Affiliations

¹ 1Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
² 2Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
³ 3Department of Urology, Renji Hospital affiliated Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
⁴ 4Thoracic Oncology Institute at Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁵ 5School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China.

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^Cdh1 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^Cdh1-Plk1 axis to control DNA damage-induced G2 checkpoint.

Keywords: Cell division; Sumoylation.

Abstract

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