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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint
Yang Wang1,2,3, Jing Tian1,2,3, Chao Huang4
11Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China.
Cell Discovery
|May 1, 2020
Summary
DNA damage triggers a p53-dependent pathway where SUMOylation regulates the G2 checkpoint. Suppressed SENP3 phosphorylation activates de-SUMOylation of Cdh1, controlling cell cycle arrest.
Area of Science:
- Cellular biology
- Molecular oncology
- DNA damage response
Background:
- p53-mediated signaling controls the G2 checkpoint via phosphorylation and ubiquitination.
- The role of protein SUMOylation in this process remains largely unexplored.
Purpose of the Study:
- To investigate the role of protein SUMOylation in p53-mediated G2 checkpoint regulation following DNA damage.
- To elucidate the molecular mechanisms linking SUMOylation to G2 arrest.
Main Methods:
- Western blotting to detect protein phosphorylation and SUMOylation.
- Immunoprecipitation to analyze protein interactions.
- Cell cycle analysis to assess G2 arrest.
- Ubiquitination assays to measure protein degradation.
Main Results:
- G2 DNA damage suppressed SENP3 phosphorylation in a p53-dependent manner.
- Suppression of SENP3 phosphorylation was essential for G2 checkpoint activation.
- SENP3 de-SUMOylated Cdh1, promoting its de-phosphorylation by Cdc14B.
- This activated the APC/CCdh1 ligase to degrade Plk1, facilitating G2 arrest.
Conclusions:
- p53-mediated inhibition of SENP3 phosphorylation is a key regulatory step in the DNA damage-induced G2 checkpoint.
- The study reveals a novel SUMOylation-dependent pathway involving SENP3, Cdh1, Cdc14B, and Plk1 in G2 checkpoint control.
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