Role of EDEM in the Release of Misfolded Glycoproteins from the Calnexin Cycle
- 28 February 2003
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 299 (5611) , 1397-1400
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 α-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.Keywords
This publication has 13 references indexed in Scilit:
- Sequential assistance of molecular chaperones and transient formation of covalent complexes during protein degradation from the ERJournal of Cell Biology, 2002
- Dissecting glycoprotein quality control in the secretory pathwayTrends in Biochemical Sciences, 2001
- Htm1p, a mannosidase‐like protein, is involved in glycoprotein degradation in yeastEMBO Reports, 2001
- A novel ER α‐mannosidase‐like protein accelerates ER‐associated degradationEMBO Reports, 2001
- Mnl1p, an α-Mannosidase-like Protein in YeastSaccharomyces cerevisiae, Is Required for Endoplasmic Reticulum-associated Degradation of GlycoproteinsJournal of Biological Chemistry, 2001
- Protein Glucosylation and Its Role in Protein FoldingAnnual Review of Biochemistry, 2000
- Role of N-oligosaccharide endoplasmic reticulum processing reactions in glycoprotein folding and degradationBiochemical Journal, 2000
- Degradation of a Short-lived Glycoprotein from the Lumen of the Endoplasmic Reticulum: The Role of N-linked Glycans and the Unfolded Protein ResponseMolecular Biology of the Cell, 1999
- Oligosaccharide Modification in the Early Secretory Pathway Directs the Selection of a Misfolded Glycoprotein for Degradation by the ProteasomeJournal of Biological Chemistry, 1999
- Role of N-linked oligosaccharide recognition, glucose trimming, and calnexin in glycoprotein folding and quality control.Proceedings of the National Academy of Sciences, 1994