N-terminal HCV core protein fragment decreases 20S proteasome activity in the presence of PA28γ

Biochem Biophys Res Commun. 2019 Feb 5;509(2):590-595. doi: 10.1016/j.bbrc.2018.12.167. Epub 2018 Dec 31.

Abstract

The Hepatitis C virus (HCV) core protein plays a crucial role in the development of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Its involvement in these diseases is reportedly abolished by a knockout of the proteasome activator PA28γ gene in transgenic mice, suggesting an interaction between the core protein and the PA28γ-proteasome system. This study found a direct interaction between the N-terminal 1-71 fragment of HCV core protein (Core71) and PA28γ in vitro, and that this interaction was found to enhance PA28γ-20S proteasome complex formation. While 20S proteasome activity was increased by PA28γ, it was significantly reduced by Core71 attachment in a dose-dependent manner. These results suggest that the Core-PA28γ interaction has an important role in regulating 20S proteasome activity and furthers our understanding of the pathogenesis of HCV.

Keywords: 20S-proteasome; HCV core protein; PA28γ.

MeSH terms

  • Autoantigens / chemistry
  • Autoantigens / metabolism*
  • Hepacivirus / chemistry
  • Hepacivirus / metabolism*
  • Hepatitis C / metabolism*
  • Hepatitis C / virology
  • Host-Pathogen Interactions
  • Humans
  • Models, Molecular
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Interaction Maps
  • Viral Core Proteins / chemistry
  • Viral Core Proteins / metabolism*

Substances

  • Autoantigens
  • Ki antigen
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus
  • Proteasome Endopeptidase Complex