Cargando…
Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins
Misfolded proteins in the endoplasmic reticulum (ER) are identified and degraded by the ER-associated degradation pathway (ERAD), a component of ER quality control. In ERAD, misfolded proteins are removed from the ER by retrotranslocation into the cytosol where they are degraded by the ubiquitin–pro...
Autores principales: | , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442213/ https://www.ncbi.nlm.nih.gov/pubmed/18573918 http://dx.doi.org/10.1083/jcb.200804053 |
_version_ | 1782156695039901696 |
---|---|
author | Scott, Daniel C. Schekman, Randy |
author_facet | Scott, Daniel C. Schekman, Randy |
author_sort | Scott, Daniel C. |
collection | PubMed |
description | Misfolded proteins in the endoplasmic reticulum (ER) are identified and degraded by the ER-associated degradation pathway (ERAD), a component of ER quality control. In ERAD, misfolded proteins are removed from the ER by retrotranslocation into the cytosol where they are degraded by the ubiquitin–proteasome system. The identity of the specific protein components responsible for retrotranslocation remains controversial, with the potential candidates being Sec61p, Der1p, and Doa10. We show that the cytoplasmic N-terminal domain of a short-lived transmembrane ERAD substrate is exposed to the lumen of the ER during the degradation process. The addition of N-linked glycan to the N terminus of the substrate is prevented by mutation of a specific cysteine residue of Sec61p, as well as a specific cysteine residue of the substrate protein. We show that the substrate protein forms a disulfide-linked complex to Sec61p, suggesting that at least part of the retrotranslocation process involves Sec61p. |
format | Text |
id | pubmed-2442213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-24422132008-12-30 Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins Scott, Daniel C. Schekman, Randy J Cell Biol Research Articles Misfolded proteins in the endoplasmic reticulum (ER) are identified and degraded by the ER-associated degradation pathway (ERAD), a component of ER quality control. In ERAD, misfolded proteins are removed from the ER by retrotranslocation into the cytosol where they are degraded by the ubiquitin–proteasome system. The identity of the specific protein components responsible for retrotranslocation remains controversial, with the potential candidates being Sec61p, Der1p, and Doa10. We show that the cytoplasmic N-terminal domain of a short-lived transmembrane ERAD substrate is exposed to the lumen of the ER during the degradation process. The addition of N-linked glycan to the N terminus of the substrate is prevented by mutation of a specific cysteine residue of Sec61p, as well as a specific cysteine residue of the substrate protein. We show that the substrate protein forms a disulfide-linked complex to Sec61p, suggesting that at least part of the retrotranslocation process involves Sec61p. The Rockefeller University Press 2008-06-30 /pmc/articles/PMC2442213/ /pubmed/18573918 http://dx.doi.org/10.1083/jcb.200804053 Text en © 2008 Scott and Schekman This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Scott, Daniel C. Schekman, Randy Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins |
title | Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins |
title_full | Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins |
title_fullStr | Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins |
title_full_unstemmed | Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins |
title_short | Role of Sec61p in the ER-associated degradation of short-lived transmembrane proteins |
title_sort | role of sec61p in the er-associated degradation of short-lived transmembrane proteins |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442213/ https://www.ncbi.nlm.nih.gov/pubmed/18573918 http://dx.doi.org/10.1083/jcb.200804053 |
work_keys_str_mv | AT scottdanielc roleofsec61pintheerassociateddegradationofshortlivedtransmembraneproteins AT schekmanrandy roleofsec61pintheerassociateddegradationofshortlivedtransmembraneproteins |