Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle

被引:366
作者
Molinari, M [1 ]
Calanca, V
Galli, C
Lucca, P
Paganetti, P
机构
[1] Inst Res Biomed, CH-6500 Bellinzona, Switzerland
[2] Novartis Pharma AG, Nervous Syst, CH-4002 Basel, Switzerland
关键词
D O I
10.1126/science.1079474
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanisms that determine how folding attempts are interrupted to target folding-incompetent proteins for endoplasmic reticulum-associated degradation (ERAD) are poorly defined. Here the alpha-mannosidase I-like protein EDEM was shown to extract misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. EDEM overexpression resulted in faster release of folding-incompetent proteins from the calnexin cycle and earlier onset of degradation, whereas EDEM down-regulation prolonged folding attempts and delayed ERAD. Up-regulation of EDEM during ER stress may promote cell recovery by clearing the calnexin cycle and by accelerating ERAD of terminally misfolded polypeptides.
引用
收藏
页码:1397 / 1400
页数:5
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