Proteasome Inhibition Leads to the Activation of All Members of the Heat-Shock-Factor Family

Eur J Biochem. 1998 Jul 15;255(2):356-62. doi: 10.1046/j.1432-1327.1998.2550356.x.

Abstract

Heat-shock proteins and molecular chaperones are involved in various cellular metabolic processes including protein synthesis and degradation. These expressions are elevated at the level of transcription by the accumulation of abnormal proteins when these metabolic processes are disturbed. Recent works suggest the induction of heat-shock proteins by the inhibiton of proteasome. To elucidate the mechanism of this induction, we examined the activation of heat-shock transcription factors by proteasome inhibitors in avian cells. Activation of the two heat-shock-inducible factors, HSF1 and HSF3, was produced by the treatment of cells with proteasome inhibitors. This activation was not produced by treatment with various other protease inhibitors. The HSF activation by proteasome inhibitors was completely blocked in the presence of the protein synthesis inhibitor cycloheximide. Unexpectedly, the development-related factor HSF2 was also activated by proteasome inhibitors, with an increase in its protein level. These results suggest that the ubiqutin-proteasome pathway may regulate all of the three HSFs by controlling the level of some regulatory factor for HSF or HSF itself, as well as controlling abnormal proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins*
  • Cell Nucleus / metabolism
  • Chickens
  • Cycloheximide / pharmacology
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • DNA-Binding Proteins / metabolism*
  • Erythroblasts
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / biosynthesis*
  • Heat-Shock Proteins / metabolism*
  • Kinetics
  • Leupeptins / pharmacology*
  • Multienzyme Complexes / metabolism*
  • Proteasome Endopeptidase Complex
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Tunicamycin / pharmacology

Substances

  • Avian Proteins
  • Cysteine Proteinase Inhibitors
  • DNA-Binding Proteins
  • HSF1 protein, human
  • HSF3 protein, Gallus gallus
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Leupeptins
  • Multienzyme Complexes
  • Trans-Activators
  • Transcription Factors
  • Tunicamycin
  • HSF2 protein, human
  • Cycloheximide
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde