Journal article
Cotranslocational Degradation Protects the Stressed Endoplasmic Reticulum from Protein Overload
Cell (Cambridge), Vol.126(4), pp.727-739
2006
Handle:
https://hdl.handle.net/2376/112503
PMID: 16923392
Abstract
The ER's capacity to process proteins is limited, and stress caused by accumulation of unfolded and misfolded proteins (ER stress) contributes to human disease. ER stress elicits the unfolded protein response (UPR), whose components attenuate protein synthesis, increase folding capacity, and enhance misfolded protein degradation. Here, we report that
P58
IPK/DNAJC3
, a UPR-responsive gene previously implicated in translational control, encodes a cytosolic cochaperone that associates with the ER protein translocation channel Sec61. P58
IPK recruits HSP70 chaperones to the cytosolic face of Sec61 and can be crosslinked to proteins entering the ER that are delayed at the translocon. Proteasome-mediated cytosolic degradation of translocating proteins delayed at Sec61 is cochaperone dependent. In
P58
IPK−/−
mice, cells with a high secretory burden are markedly compromised in their ability to cope with ER stress. Thus, P58
IPK is a key mediator of cotranslocational ER protein degradation, and this process likely contributes to ER homeostasis in stressed cells.
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Details
- Title
- Cotranslocational Degradation Protects the Stressed Endoplasmic Reticulum from Protein Overload
- Creators
- Seiichi Oyadomari - Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016 USAChi Yun - Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016 USAEdward A Fisher - Department of Medicine, New York University School of Medicine, New York, NY 10016 USANicola Kreglinger - Department of Medicine, New York University School of Medicine, New York, NY 10016 USAGert Kreibich - Department of Cell Biology, New York University School of Medicine, New York, NY 10016 USAMiho Oyadomari - Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016 USAHeather P Harding - Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016 USAAlan G Goodman - Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 USAHanna Harant - Novartis Institutes for BioMedical Research, A-1235 Vienna, AustriaJennifer L Garrison - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94107 USAJack Taunton - Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94107 USAMichael G Katze - Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 USADavid Ron - Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016 USA
- Publication Details
- Cell (Cambridge), Vol.126(4), pp.727-739
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- Elsevier Inc
- Identifiers
- 99900548167101842
- Language
- English
- Resource Type
- Journal article