Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle |
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Authors: | Molinari Maurizio Calanca Verena Galli Carmela Lucca Paola Paganetti Paolo |
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Affiliation: | Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland. Maurizio.molinari@irb.unisi.ch |
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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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