A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response

Cell. 1996 Nov 1;87(3):391-404. doi: 10.1016/s0092-8674(00)81360-4.


Cells respond to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing transcription of genes encoding ER-resident proteins. The information is transmitted from the ER lumen to the nucleus by an intracellular signaling pathway, the unfolded protein response (UPR). We have identified a basic-leucine zipper transcription factor, Hac1p, that is required for the UPR and binds to the UPR element in the promoter of UPR-regulated genes. Surprisingly, Hac1p is found in UPR-activated cells only, and its level is controlled by regulated splicing of its mRNA. Splicing replaces the C-terminal tail of Hac1p with a different peptide that renders Hac1p more resistant to an otherwise extremely rapid ubiquitin-dependent degradation. We propose that the complex regulation of Hac1p expression serves to provide multiple levels at which the UPR can be controlled.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Basic-Leucine Zipper Transcription Factors
  • DNA, Fungal / genetics
  • Endopeptidases / metabolism
  • Endoplasmic Reticulum / physiology*
  • Fungal Proteins / genetics*
  • Fungal Proteins / physiology
  • Gene Expression Regulation, Fungal*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Molecular Chaperones / biosynthesis*
  • Molecular Chaperones / genetics
  • Molecular Sequence Data
  • Phenotype
  • Protein Folding*
  • Protein-Serine-Threonine Kinases*
  • RNA Splicing*
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / genetics*
  • Repressor Proteins / physiology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors*
  • Transcription, Genetic
  • Ubiquitins / metabolism


  • Basic-Leucine Zipper Transcription Factors
  • DNA, Fungal
  • Fungal Proteins
  • HAC1 protein, S cerevisiae
  • Membrane Glycoproteins
  • Molecular Chaperones
  • RNA, Fungal
  • RNA, Messenger
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Ubiquitins
  • IRE1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • Endopeptidases