JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 30 January 2006. doi:10.1083/jcb.200507057
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 3, 383-393
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2726K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oda, Y.
Right arrow Articles by Mori, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oda, Y.
Right arrow Articles by Mori, K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation



Yukako Oda1,2, Tetsuya Okada3, Hiderou Yoshida3,4, Randal J. Kaufman5,6, Kazuhiro Nagata1,2, and Kazutoshi Mori3

1 Department of Molecular and Cellular Biology Institute for Frontier Medical Sciences, and 3 Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
2 Core Research for Evolutional Science and Technology and 4 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 332-0012, Japan
5 Howard Hughes Medical Institute and 6 Department of Biological Chemistry and Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109

Correspondence to Kazutoshi Mori: kazu.mori{at}bio.mbox.media.kyoto-u.ac.jp

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 {alpha}-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.

Y. Oda and T. Okada contributed equally to this paper.

Abbreviations used in this paper: {alpha}1-PI, {alpha}1-proteinase inhibitor; BiP, binding protein; DIG, digoxigenin; EDEM, ER degradation enhancing {alpha}-mannosidase–like protein; ERAD, ER-associated degradation; GAPDH, glyceraldehyde- 3-phosphate dehydrogenase; HC, heavy chain; HEK, human embryonic kidney; MEF, mouse embryonic fibroblast; NHK, null Hong Kong; shRNA, short hairpin RNA; tv, transcriptional variant; UPR, unfolded protein response; VCP, vasolin-containing protein.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents