title: The Role of Lectin-Carbohydrate Interactions in the Regulation of ER-Associated Protein Degradation.
abstract: Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER) membrane in an unfolded form. In the ER they are restricted to a quality control system that ensures correct folding or eventual degradation of improperly folded polypeptides. Mannose trimming of N-glycans on newly synthesized proteins plays an important role in the recognition and sorting of terminally misfolded glycoproteins for ER-associated protein degradation (ERAD). In this process misfolded proteins are retrotranslocated into the cytosol, polyubiquitinated, and eventually degraded by the proteasome. The mechanism by which misfolded glycoproteins are recognized and recruited to the degradation machinery has been extensively studied during last decade. In this review, we focus on ER degradation-enhancing α-mannosidase-like protein (EDEM) family proteins that seem to play a key role in the discrimination between proteins undergoing a folding process and terminally misfolded proteins directed for degradation. We describe interactions of EDEM proteins with other components of the ERAD machinery, as well as with various protein substrates. Carbohydrate-dependent interactions together with N-glycan-independent interactions seem to regulate the complex process of protein recognition and direction for proteosomal degradation.
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland. monika.slominska@biol.ug.edu.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Słomińska-Wojewódzka
authors.affiliation: Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, Norway. kirsten.sandvig@ibv.uio.no.|Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway. kirsten.sandvig@ibv.uio.no.|Department of Biosciences, University of Oslo, 0316 Oslo, Norway. kirsten.sandvig@ibv.uio.no.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sandvig
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation / Q000235:genetics*; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D021381:Protein Transport; D059748:Proteolysis; D015398:Signal Transduction; D054875:Ubiquitination; D043323:alpha-Mannosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: C486654:EDEM1 protein, human; D006023:Glycoproteins; D037102:Lectins; D008565:Membrane Proteins; D011134:Polysaccharides; C497155:EDEM2 protein, human; D043323:alpha-Mannosidase; D046988:Proteasome Endopeptidase Complex
keywords: EDEM chaperone proteins; ERAD; N-glycan