A genetic link between the unfolded protein response and vesicle formation from the endoplasmic reticulum

Biochem Biophys Res Commun. 2002 Aug 23;296(3):568-74. doi: 10.1016/s0006-291x(02)00923-3.


Protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus is mediated by transport vesicles coated with the coat protein complex II (COPII). In the process of searching for novel factors that participate in the formation of COPII-coated vesicles (COPII vesicles), we isolated high-copy suppressors of a sec24-20 mutant defective in COPII vesicle formation from the ER at the restrictive temperature. Unexpectedly, one of them was identified as HAC1, a gene encoding the basic leucine-zipper type transcription factor Hac1p. Hac1p is essential for a signaling cascade activated by ER stress, termed the unfolded protein response (UPR) pathway, that leads from the ER to the nucleus. Overexpression of another UPR-related gene IRE1, which encodes an ER-resident transmembrane protein kinase/ribonuclease, also suppressed the growth defect of the sec24-20 mutant in a HAC1-dependent manner. Moreover, overexpression of IRE1 specifically suppressed growth defects of other sec mutants defective in COPII vesicle formation. These findings suggest that the activation of the UPR affects ER-to-Golgi transport via stimulation of COPII vesicle formation from the ER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors
  • COP-Coated Vesicles / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Genes, Suppressor
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation
  • Protein Folding
  • Protein Transport
  • Protein-Serine-Threonine Kinases*
  • RNA, Fungal / biosynthesis
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction
  • Transcription Factors*


  • Basic-Leucine Zipper Transcription Factors
  • Fungal Proteins
  • HAC1 protein, S cerevisiae
  • Membrane Glycoproteins
  • Membrane Proteins
  • RNA, Fungal
  • Repressor Proteins
  • SEC24 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • IRE1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases