Yeast unfolded protein response pathway regulates expression of genes for anti-oxidative stress and for cell surface proteins

Genes Cells. 2006 Jan;11(1):59-69. doi: 10.1111/j.1365-2443.2005.00921.x.


The unfolded protein response (UPR) is a cellular protective event against endoplasmic reticulum (ER) stress. In the yeast UPR signaling pathway, the ER-located transmembrane protein Ire1 promotes splicing of the HAC1 premRNA (HAC1(u)) to produce the translatable transcription factor mRNA (HAC1i). We generated a HAC1i gene-bearing strain, in which the UPR pathway was constitutively activated, and compared its gene expression profile with that of a Deltaire1 HAC1u strain using cDNA microarray technology. Comparison of the gene expression profile was also performed between non-stressed wild-type cells and those exposed to ER stress. Genes for which the expression level was significantly changed in both of these experiments were categorized as targets of the Ire1-HAC1 signaling pathway. This analysis revealed that in addition to the previously known UPR targets, some anti-oxidative stress genes were up-regulated by the Ire1-HAC1 pathway, possibly in order to reduce reactive oxygen species produced during the cellular response to ER stress. Moreover, we categorized 15 genes as those down-regulated by the UPR, most of which seem to encode cell surface or extracellular proteins. This UPR-mediated gene repression may alleviate the load of client proteins targeted to the ER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Down-Regulation
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Profiling
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Oxidative Stress*
  • Peroxidases / metabolism
  • Protein Folding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation


  • Basic-Leucine Zipper Transcription Factors
  • HAC1 protein, S cerevisiae
  • Membrane Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • YAP1 protein, S cerevisiae
  • Peroxidases
  • Tsa1 protein, S cerevisiae