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. 2003 Feb 28;299(5611):1397-400.
doi: 10.1126/science.1079474.

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

Maurizio Molinari  1 , Verena Calanca, Carmela Galli, Paola Lucca, Paolo Paganetti
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Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle

Maurizio Molinari et al. Science. .

Abstract

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.

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