USP3 stabilizes p53 protein through its deubiquitinase activity

Biochem Biophys Res Commun. 2017 Oct 14;492(2):178-183. doi: 10.1016/j.bbrc.2017.08.036. Epub 2017 Aug 12.

Abstract

p53 is the guardian of the genome integrity and the degradation of p53 protein is mediated by MDM2. Here we report that USP3 interacts with p53 and regulates p53 stability. Depletion of USP3 lead to accelerated degradation of p53 in normal cells thereby enhanced cell proliferation and transformation. Reconstitution of wildtype USP3, but not the USP3 C168S mutant, restored the stability of p53 protein and inhibited cell proliferation and transformation. These findings suggest that USP3 is an important regulator of p53 and regulates normal cell transformation.

Keywords: Cell proliferation; Cell transformation; Deubiquitination; USP3; p53.

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cell Transformation, Neoplastic
  • Humans
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Interaction Maps
  • Protein Stability
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin-Specific Proteases / analysis
  • Ubiquitin-Specific Proteases / metabolism*
  • Ubiquitination*

Substances

  • Tumor Suppressor Protein p53
  • USP3 protein, human
  • Ubiquitin-Specific Proteases