The SUMO-specific protease SENP1 deSUMOylates p53 and regulates its activity

Krishna M. Chauhan, Yingxiao Chen, Yiyi Chen, Andrew T. Liu, Xiao Xin Sun, Mu Shui Dai

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The stability and activity of the p53 tumor suppressor protein are tightly regulated by various posttranslational modifications, including SUMOylation. p53 can be modified by both SUMO1 and SUMO2, although how SUMOylation regulates p53 activity is still obscure. Whether p53 activity is directly regulated by deSUMOylation is also unclear. Here, we show that SENP1, a SUMO-specific protease implicated in pro-oncogenic roles, is a p53 deSUMOylating enzyme. SENP1 interacts with p53 and deSUMOylates p53 in cells and in vitro. Knockdown of SENP1 markedly induced p53 transactivation activity. We further show that SENP1 depletion synergizes with DNA damage-inducing agent etoposide to induce p53 activation and the expression of p21, leading to synergistic growth inhibition of cancer cells. Our results reveal that SENP1 is a critical p53 deSUMOylating enzyme and a promising therapeutic target in wild-type p53 containing cancer cells.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalJournal of cellular biochemistry
Issue number2
StatePublished - Feb 2021


  • SENP1
  • SUMO
  • SUMO protease
  • SUMOylation
  • p53

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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