The deubiquitinating enzyme USP24 is a regulator of the UV damage response

Ling Zhang, Leah Nemzow, Hua Chen, Abigail Lubin, Xi Rong, Zhongyi Sun, Thomas K. Harris, Feng Gong

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Regulation of p53 by ubiquitination and deubiquitination is important for its function. In this study, we demonstrate that USP24 deubiquitinates p53 in human cells. Functional USP24 is required for p53 stabilization, and p53 destabilization in USP24-depleted cells can be corrected by the forced expression of USP24. We show that USP24 depletion renders cells resistant to apoptosis after UV irradiation, consistent with the requirement of USP24 for p53 stabilization and PUMA activation invivo. Additionally, purified USP24 protein is able to cleave ubiquitinated p53 invitro. Importantly, cells with USP24 depletion exhibited significantly elevated mutation rates at the endogenous HPRT locus, implying an important role for USP24 in maintaining genome stability. Our data reveal that the USP24 deubiquitinase regulates the DNA damage response by directly targeting the p53 tumor suppressor.

Original languageEnglish (US)
Pages (from-to)140-147
Number of pages8
JournalCell Reports
Volume10
Issue number2
DOIs
StatePublished - Jan 13 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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