title: EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin.
abstract: Terminally misfolded proteins in the endoplasmic reticulum (ER) are retrotranslocated to the cytoplasm and degraded by proteasomes through a mechanism known as ER-associated degradation (ERAD). EDEM, a postulated Man8B-binding protein, accelerates the degradation of misfolded proteins in the ER. Here, EDEM was shown to interact with calnexin, but not with calreticulin, through its transmembrane region. Both binding of substrates to calnexin and their release from calnexin were required for ERAD to occur. Overexpression of EDEM accelerated ERAD by promoting the release of terminally misfolded proteins from calnexin. Thus, EDEM appeared to function in the ERAD pathway by accepting substrates from calnexin.
authors.affiliation: Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Oda
authors.forename: Nobuko
authors.initials: N
authors.lastname: Hosokawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Wada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D037281:Calnexin / Q000378:metabolism*; D037282:Calreticulin / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000378:metabolism*; D054836:Indolizidines
chemical_list: D000111:Acetylcysteine; D037281:Calnexin; D037282:Calreticulin; D006023:Glycoproteins; D007212:Indolizines; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D000515:alpha 1-Antitrypsin; C486654:EDEM1 protein, human; C067713:lactacystin; C037806:castanospermine; D054836:Indolizidines