P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint

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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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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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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
PubMed

Insights

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.
Keywords:
Cell divisionSumoylation

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