title: A luminal flavoprotein in endoplasmic reticulum-associated degradation.
abstract: The quality control system of the endoplasmic reticulum (ER) discriminates between native and nonnative proteins. The latter are degraded by the ER-associated degradation (ERAD) pathway. Whereas many cytosolic and membrane components of this system are known, only few luminal players have been identified. In this study, we characterize ERFAD (ER flavoprotein associated with degradation), an ER luminal flavoprotein that functions in ERAD. Upon knockdown of ERFAD, the degradation of the ERAD model substrate ribophorin 332 is delayed, and the overall level of polyubiquitinated cellular proteins is decreased. We also identify the ERAD components SEL1L, OS-9 and ERdj5, a known reductase of ERAD substrates, as interaction partners of ERFAD. Our data show that ERFAD facilitates the dislocation of certain ERAD substrates to the cytosol, and we discuss the findings in relation to a potential redox function of the protein.
authors.affiliation: Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Riemer
authors.forename: Christian
authors.initials: C
authors.lastname: Appenzeller-Herzog
authors.forename: Linda
authors.initials: L
authors.lastname: Johansson
authors.forename: Bernd
authors.initials: B
authors.lastname: Bodenmiller
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
authors.forename: Lars
authors.initials: L
authors.lastname: Ellgaard
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005420:Flavoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D037102:Lectins; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D016415:Sequence Alignment; D054875:Ubiquitination
chemical_list: C471179:DNAJC10 protein, human; D005420:Flavoproteins; D050956:HSP40 Heat-Shock Proteins; D037102:Lectins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C098898:OS9 protein, human; D011506:Proteins; C117384:SEL1L protein, human
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