title: Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Travers
authors.forename: C K
authors.initials: CK
authors.lastname: Patil
authors.forename: L
authors.initials: L
authors.lastname: Wodicka
authors.forename: D J
authors.initials: DJ
authors.lastname: Lockhart
authors.forename: J S
authors.initials: JS
authors.lastname: Weissman
authors.forename: P
authors.initials: P
authors.lastname: Walter
mesh_terms: D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016681:Genome, Fungal; D016296:Mutagenesis; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D005656:Fungal Proteins