The deubiquitinase USP38 promotes cell proliferation through stabilizing c-Myc

Int J Biochem Cell Biol. 2021 Aug:137:106023. doi: 10.1016/j.biocel.2021.106023. Epub 2021 Jun 5.

Abstract

The oncoprotein c-Myc is a master transcription factor that regulates the expression of a large number of genes involved in cell cycle, cell growth, and cell metabolism. Hence, it is important to keep the level of c-Myc under control. There are many proteins responsible for the degradation of c-Myc. However, the deubiquitinase-mediated stabilization of c-Myc remains less well understood. In this study, we found that USP38, an ubiquitin-specific protease, regulates the levels and function of c-Myc. USP38 can inhibit the polyubiquitination of c-Myc, thereby increasing c-Myc stability. Functionally, USP38 is able to promote cell proliferation via a c-Myc dependent manner. Mechanistically, USP38 physically interacts with FBW7α and abolishes FBW7α-mediated degradation of c-Myc. Furthermore, USP38 can restore the inhibitory effect of FBW7α on proliferation. Taken together, our study uncovers a novel role for USP38 in the regulation of c-Myc abundance and stability.

Keywords: Deubiquitination; Stability; USP38; c-Myc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Proto-Oncogene Proteins c-myc / chemistry*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Tumor Cells, Cultured
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism*
  • Ubiquitination*

Substances

  • Biomarkers, Tumor
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • USP38 protein, human
  • Ubiquitin-Specific Proteases