Degradation of proteins from the ER of S. cerevisiae requires an intact unfolded protein response pathway

Mol Cell. 2000 Apr;5(4):729-35. doi: 10.1016/s1097-2765(00)80251-8.

Abstract

To dissect the requirements of membrane protein degradation from the ER, we expressed the mouse major histocompatibility complex class I heavy chain H-2K(b) in yeast. Like other proteins degraded from the ER, unassembled H-2K(b) heavy chains are not transported to the Golgi but are degraded in a proteasome-dependent manner. The overexpression of H-2K(b) heavy chains induces the unfolded protein response (UPR). In yeast mutants unable to mount the UPR, H-2K(b) heavy chains are greatly stabilized. This defect in degradation is suppressed by the expression of the active form of Hac1p, the transcription factor that upregulates UPR-induced genes. These results indicate that induction of the UPR is required for the degradation of protein substrates from the ER.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Endoplasmic Reticulum / metabolism*
  • Fungal Proteins / metabolism
  • Gene Expression Regulation
  • H-2 Antigens / genetics
  • H-2 Antigens / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Molecular Chaperones / biosynthesis*
  • Oligonucleotide Array Sequence Analysis
  • Protein Denaturation
  • Protein Folding*
  • Protein-Serine-Threonine Kinases*
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction

Substances

  • Fungal Proteins
  • H-2 Antigens
  • H-2Kb protein, mouse
  • HSP70 Heat-Shock Proteins
  • KAR2 protein, yeast
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • IRE1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases