Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Oda, Yukako, Okada, Tetsuya, Yoshida, Hiderou, Kaufman, Randal J., Nagata, Kazuhiro, Mori, Kazutoshi
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
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
_version_ 1782137359477768192
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
work_keys_str_mv AT odayukako derlin2andderlin3areregulatedbythemammalianunfoldedproteinresponseandarerequiredforerassociateddegradation
AT okadatetsuya derlin2andderlin3areregulatedbythemammalianunfoldedproteinresponseandarerequiredforerassociateddegradation
AT yoshidahiderou derlin2andderlin3areregulatedbythemammalianunfoldedproteinresponseandarerequiredforerassociateddegradation
AT kaufmanrandalj derlin2andderlin3areregulatedbythemammalianunfoldedproteinresponseandarerequiredforerassociateddegradation
AT nagatakazuhiro derlin2andderlin3areregulatedbythemammalianunfoldedproteinresponseandarerequiredforerassociateddegradation
AT morikazutoshi derlin2andderlin3areregulatedbythemammalianunfoldedproteinresponseandarerequiredforerassociateddegradation