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PMID: 18315532 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The recognition and retrotranslocation of misfolded proteins from the endoplasmic reticulum.

Traffic (Copenhagen, Denmark) ·Vol. 9 ·No. 6 ·2008-06-00 ·Pages 861-70

Nakatsukasa K, Brodsky JL

Abstract

Secretory and membrane proteins that fail to fold in the endoplasmic reticulum (ER) are retained and may be sorted for ER-associated degradation (ERAD). During ERAD, ER-associated components such as molecular chaperones and lectins recognize folding intermediates and specific oligosaccharyl modifications on ERAD substrates. Substrates selected for ERAD are then targeted for ubiquitin- and proteasome-mediated degradation. Because the catalytic steps of the ubiquitin-proteasome system reside in the cytoplasm, soluble ERAD substrates that reside in the ER lumen must be retrotranslocated back to the cytoplasm prior to degradation. In contrast, it has been less clear how polytopic, integral membrane substrates are delivered to enzymes required for ubiquitin conjugation and to the proteasome. In this review, we discuss recent studies addressing how ERAD substrates are recognized, ubiquitinated and delivered to the proteasome and then survey current views of how soluble and integral membrane substrates may be retrotranslocated.

MeSH Terms
Animals Endoplasmic Reticulum/metabolism Proteasome Endopeptidase Complex/metabolism Protein Folding Protein Transport Proteins/metabolism Solubility Substrate Specificity Ubiquitin/metabolism
Chemicals
Proteins Ubiquitin Proteasome Endopeptidase Complex
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Nakatsukasa Kunio
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Brodsky Jeffrey L
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Article Info
Journal
Traffic (Copenhagen, Denmark)
Abbr.
Traffic
ISSN
1600-0854
DOI
10.1111/j.1600-0854.2008.00729.x
Published
2008-06-00
Epub
2008-00-24
Pages
861-70
Language
English
Region
England
NLM ID
100939340
PMCID
PMC2754126
Subset
IM
Grants
NCRR NIH HHS · P41 RR006009-13S10160 · United States
NHLBI NIH HHS · HL58541 · United States
NHLBI NIH HHS · R01 HL058541 · United States
NIGMS NIH HHS · R01 GM075061 · United States
NIGMS NIH HHS · R01 GM075061-02 · United States
NIGMS NIH HHS · GM075061 · United States
External Links
PubMed source DOI: 10.1111/j.1600-0854.2008.00729.x PMC Full Text View journal details
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