Functional and Genomic Analyses Reveal an Essential Coordination between the Unfolded Protein Response and ER-Associated Degradation

The unfolded protein response (UPR) regulates gene expression in response to stress in the endoplasmic reticulum (ER). We determined the transcriptional scope of the UPR using DNA microarrays. Rather than regulating only ER-resident chaperones and phospholipid biosynthesis, as anticipated from earli...

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Bibliographic Details
Published in:Cell 2000-04, Vol.101 (3), p.249-258
Main Authors: Travers, Kevin J, Patil, Christopher K, Wodicka, Lisa, Lockhart, David J, Weissman, Jonathan S, Walter, Peter
Format: Article
Language:English
Subjects:
Endoplasmic Reticulum, Rough - metabolism
Fungal Proteins - genetics
Fungal Proteins - metabolism
Genome, Fungal
Mutagenesis
Protein Folding
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae - physiology
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Summary:The unfolded protein response (UPR) regulates gene expression in response to stress in the endoplasmic reticulum (ER). We determined the transcriptional scope of the UPR using DNA microarrays. Rather than regulating only ER-resident chaperones and phospholipid biosynthesis, as anticipated from earlier work, the UPR affects multiple ER and secretory pathway functions. Studies of UPR targets engaged in ER-associated protein degradation (ERAD) reveal an intimate coordination between these responses: efficient ERAD requires an intact UPR, and UPR induction increases ERAD capacity. Conversely, loss of ERAD leads to constitutive UPR induction. Finally, simultaneous loss of ERAD and the UPR greatly decreases cell viability. Thus, the UPR and ERAD are dynamic responses required for the coordinated disposal of misfolded proteins even in the absence of acute stress.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80835-1