HSC90 is required for nascent hepatitis C virus core protein stability in yeast cells

FEBS Lett. 2012 Jul 30;586(16):2318-25. doi: 10.1016/j.febslet.2012.05.023. Epub 2012 May 31.

Abstract

Hepatitis C virus core protein (Core) contributes to HCV pathogenicity. Here, we demonstrate that Core impairs growth in budding yeast. We identify HSP90 inhibitors as compounds that reduce intracellular Core protein level and restore yeast growth. Our results suggest that HSC90 (Hsc82) may function in the protection of the nascent Core polypeptide against degradation in yeast and the C-terminal region of Core corresponding to the organelle-interaction domain was responsible for Hsc82-dependent stability. The yeast system may be utilized to select compounds that can direct the C-terminal region to reduce the stability of Core protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor / virology
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Viral*
  • Green Fluorescent Proteins / metabolism
  • Hepacivirus / metabolism*
  • Humans
  • Microscopy, Confocal / methods
  • Microscopy, Fluorescence / methods
  • Peptides / chemistry
  • Plasmids / metabolism
  • Protein Conformation
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / virology*
  • Time Factors
  • Viral Core Proteins / metabolism*

Substances

  • Fungal Proteins
  • Peptides
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus
  • Green Fluorescent Proteins