DNAJC5 promotes hepatocellular carcinoma cells proliferation though regulating SKP2 mediated p27 degradation

Biochim Biophys Acta Mol Cell Res. 2021 May;1868(6):118994. doi: 10.1016/j.bbamcr.2021.118994. Epub 2021 Mar 2.

Abstract

DNAJC5 (DnaJ heat shock protein family (Hsp40) member C5), also known as cysteine tandem protein (CSPα), is important for maintaining the normal function of nerve tissues, but its oncogenic function remains unknown. Here, we report a unique mechanism underlying the oncogenic function of DNAJC5. DNAJC5 protein expression is highly detectable in human hepatocellular carcinoma (HCC) tissues and is strongly related to a poor prognosis among HCC patients. DNAJC5 overexpression promotes HCC cell proliferation and reduced the ratio of cells in G1 phase of the cell cycle. Furthermore, DNAJC5 interacts with SKP2 and enhances the degradation of p27 (a cyclin-dependent kinase inhibitor1B) by promoting formation of the SKP2-p27 complex. In contrast, DNAJC5 knockdown rescues the SKP2-mediated decrease in p27 protein levels. These results reveal that the DNAJC5-SKP2-p27 pathway is a novel mechanism for the oncogenic function of DNAJC5 in HCC.

Keywords: Cell proliferation; DNAJC5; HCC; SKP2; p27.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HEK293 Cells
  • HSP40 Heat-Shock Proteins / genetics
  • HSP40 Heat-Shock Proteins / metabolism*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Prognosis
  • Proteolysis
  • S-Phase Kinase-Associated Proteins / metabolism*
  • Up-Regulation*

Substances

  • CDKN1B protein, human
  • HSP40 Heat-Shock Proteins
  • Membrane Proteins
  • S-Phase Kinase-Associated Proteins
  • SKP2 protein, human
  • cysteine string protein
  • Cyclin-Dependent Kinase Inhibitor p27