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Science 28 February 2003:
Vol. 299. no. 5611, pp. 1397 - 1400
DOI: 10.1126/science.1079474
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Reports

Role of EDEM in the Release of Misfolded Glycoproteins from the Calnexin Cycle

Maurizio Molinari,1* Verena Calanca,1 Carmela Galli,1 Paola Lucca,1 Paolo Paganetti2

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.

1 Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
2 Nervous System, Novartis Pharma AG, CH-4002 Basel, Switzerland.
*   To whom correspondence should be addressed. E-mail: Maurizio.molinari{at}irb.unisi.ch

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