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Title: EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step.
Authors: Ninagawa, Satoshi  kyouindb  KAKEN_id
Okada, Tetsuya
Sumitomo, Yoshiki
Kamiya, Yukiko
Kato, Koichi
Horimoto, Satoshi
Ishikawa, Tokiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-1718-6764 (unconfirmed)
Takeda, Shunichi
Sakuma, Tetsushi
Yamamoto, Takashi
Mori, Kazutoshi  kyouindb  KAKEN_id
Author's alias: 蜷川, 暁
岡田, 徹也
森, 和俊
Issue Date: 4-Aug-2014
Publisher: Rockefeller University Press
Journal title: The Journal of cell biology
Volume: 206
Issue: 3
Start page: 347
End page: 356
Abstract: Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation (gpERAD) in which Htm1-mediated mannose trimming from the oligosaccharide Man8GlcNAc2 to Man7GlcNAc2 is the rate-limiting step in yeast. In contrast, the roles of the three Htm1 homologues (EDEM1/2/3) in mammalian gpERAD have remained elusive, with a key controversy being whether EDEMs function as mannosidases or as lectins. We therefore conducted transcription activator-like effector nuclease-mediated gene knockout analysis in human cell line and found that all endogenous EDEMs possess mannosidase activity. Mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1. Most surprisingly, the upstream mannose trimming from Man9GlcNAc2 to Man8GlcNAc2 is conducted mainly by EDEM2, which was previously considered to lack enzymatic activity. Based on the presence of two rate-limiting steps in mammalian gpERAD, we propose that mammalian cells double check gpERAD substrates before destruction by evolving EDEM2, a novel-type Htm1 homologue that catalyzes the first mannose trimming step from Man9GlcNAc2.
Description: 構造異常糖タンパク質の分解に必須な糖鎖刈り込み機構を解明 -最新ゲノム編集解析により醜いアヒルの子が美しい白鳥に変身-. 京都大学プレスリリース. 2014-09-02.
Rights: © 2014 by 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
URI: http://hdl.handle.net/2433/189557
DOI(Published Version): 10.1083/jcb.201404075
PubMed ID: 25092655
Related Link: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2014/140902_1.htm
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