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Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation
Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be refolded or degraded to maintain the homeostasis of the ER. Components of both productive folding and ER-associated degradation (ERAD) mechanisms are known to be up-regulated by the unfolded protein response (UPR). We...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063648/ https://www.ncbi.nlm.nih.gov/pubmed/16449189 http://dx.doi.org/10.1083/jcb.200507057 |
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author | Oda, Yukako Okada, Tetsuya Yoshida, Hiderou Kaufman, Randal J. Nagata, Kazuhiro Mori, Kazutoshi |
author_facet | Oda, Yukako Okada, Tetsuya Yoshida, Hiderou Kaufman, Randal J. Nagata, Kazuhiro Mori, Kazutoshi |
author_sort | Oda, Yukako |
collection | PubMed |
description | Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be refolded or degraded to maintain the homeostasis of the ER. Components of both productive folding and ER-associated degradation (ERAD) mechanisms are known to be up-regulated by the unfolded protein response (UPR). We describe two novel components of mammalian ERAD, Derlin-2 and -3, which show weak homology to Der1p, a transmembrane protein involved in yeast ERAD. Both Derlin-2 and -3 are up-regulated by the UPR, and at least Derlin-2 is a target of the IRE1 branch of the response, which is known to up-regulate ER degradation enhancing α-mannosidase–like protein (EDEM) and EDEM2, receptor-like molecules for misfolded glycoprotein. Overexpression of Derlin-2 or -3 accelerated degradation of misfolded glycoprotein, whereas their knockdown blocked degradation. Derlin-2 and -3 are associated with EDEM and p97, a cytosolic ATPase responsible for extraction of ERAD substrates. These findings indicate that Derlin-2 and -3 provide the missing link between EDEM and p97 in the process of degrading misfolded glycoproteins. |
format | Text |
id | pubmed-2063648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20636482007-11-29 Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation Oda, Yukako Okada, Tetsuya Yoshida, Hiderou Kaufman, Randal J. Nagata, Kazuhiro Mori, Kazutoshi J Cell Biol Research Articles Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be refolded or degraded to maintain the homeostasis of the ER. Components of both productive folding and ER-associated degradation (ERAD) mechanisms are known to be up-regulated by the unfolded protein response (UPR). We describe two novel components of mammalian ERAD, Derlin-2 and -3, which show weak homology to Der1p, a transmembrane protein involved in yeast ERAD. Both Derlin-2 and -3 are up-regulated by the UPR, and at least Derlin-2 is a target of the IRE1 branch of the response, which is known to up-regulate ER degradation enhancing α-mannosidase–like protein (EDEM) and EDEM2, receptor-like molecules for misfolded glycoprotein. Overexpression of Derlin-2 or -3 accelerated degradation of misfolded glycoprotein, whereas their knockdown blocked degradation. Derlin-2 and -3 are associated with EDEM and p97, a cytosolic ATPase responsible for extraction of ERAD substrates. These findings indicate that Derlin-2 and -3 provide the missing link between EDEM and p97 in the process of degrading misfolded glycoproteins. The Rockefeller University Press 2006-01-30 /pmc/articles/PMC2063648/ /pubmed/16449189 http://dx.doi.org/10.1083/jcb.200507057 Text en Copyright © 2006, The Rockefeller University Press 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.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Oda, Yukako Okada, Tetsuya Yoshida, Hiderou Kaufman, Randal J. Nagata, Kazuhiro Mori, Kazutoshi Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation |
title | Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation |
title_full | Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation |
title_fullStr | Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation |
title_full_unstemmed | Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation |
title_short | Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation |
title_sort | derlin-2 and derlin-3 are regulated by the mammalian unfolded protein response and are required for er-associated degradation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063648/ https://www.ncbi.nlm.nih.gov/pubmed/16449189 http://dx.doi.org/10.1083/jcb.200507057 |
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