The unfolded protein response regulates multiple aspects of secretory and membrane protein biogenesis and endoplasmic reticulum quality control

Davis T W Ng, Eric Spear, Peter Walter

Research output: Contribution to journalArticle

Abstract

The unfolded protein response (UPR) is an intracellular signaling pathway that relays signals from the lumen of the ER to activate target genes in the nucleus. We devised a genetic screen in the yeast Saccharomyces cerevisiae to isolate mutants that are dependent on activation of the pathway for viability. Using this strategy, we isolated mutants affecting various aspects of ER function, including protein translocation, folding, glycosylation, glycosylphosphatidylinositol modification, and ER-associated protein degradation (ERAD). Extending results gleaned from the genetic studies, we demonstrate that the UPR regulates trafficking of proteins at the translocon to balance the needs of biosynthesis and ERAD. The approach also revealed connections of the UPR to other regulatory pathways. In particular, we identified SON1/RPN4, a recently described transcriptional regulator for genes encoding subunits of the proteasome. Our genetic strategy, therefore, offers a powerful means to provide insight into the physiology of the UPR and to identify novel genes with roles in many aspects of secretory and membrane protein biogenesis.

Original languageEnglish (US)
Pages (from-to)77-88
Number of pages12
JournalJournal of Cell Biology
Volume150
Issue number1
DOIs
StatePublished - Jul 10 2000
Externally publishedYes

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Unfolded Protein Response
Endoplasmic Reticulum
Quality Control
Membrane Proteins
Protein Transport
Proteolysis
Glycosylphosphatidylinositols
Protein Folding
Proteasome Endopeptidase Complex
Regulator Genes
Glycosylation
Genes
Saccharomyces cerevisiae
Signal Transduction
Yeasts

Keywords

  • Gene regulation
  • Glycosylation
  • Protein degradation
  • Protein maturation
  • Protein translocation

ASJC Scopus subject areas

  • Cell Biology

Cite this

The unfolded protein response regulates multiple aspects of secretory and membrane protein biogenesis and endoplasmic reticulum quality control. / Ng, Davis T W; Spear, Eric; Walter, Peter.

In: Journal of Cell Biology, Vol. 150, No. 1, 10.07.2000, p. 77-88.

Research output: Contribution to journalArticle

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