title: CSN5 binds to misfolded CFTR and promotes its degradation.
abstract: Cystic fibrosis is mainly caused by mutations that interfere with the biosynthetic folding of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The aim of this study was to find cellular proteins interacting with CFTR and regulating its processing. We have used a genetic screen in yeast to identify such proteins and identified CSN5 that interacted with the third cytoplasmic loop of CFTR. CSN5 is the 5th component of the COP9 signalosome, a complex of eight subunits that shares significant homologies to the lid subcomplex of the 26S proteasome and controls the stability of many proteins. The present study shows that CSN5 associates with the core-glycosylated form of CFTR and suggests that this association targets misfolded CFTR to the degradative pathway. Identifying CSN5 as a new component of the degradative pathway is an important step towards the goal of unraveling the sorting between misfolded and correctly folded CFTR proteins.
authors.affiliation: INSERM U841, Département de Génétique, Equipe 11, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, Créteil, F-94010, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Tanguy
authors.forename: Loïc
authors.initials: L
authors.lastname: Drévillon
authors.forename: Nicole
authors.initials: N
authors.lastname: Arous
authors.forename: Afia
authors.initials: A
authors.lastname: Hasnain
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hinzpeter
authors.forename: Janine
authors.initials: J
authors.lastname: Fritsch
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Pascale
authors.initials: P
authors.lastname: Fanen
mesh_terms: D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae; D013267:Stilbenes / Q000494:pharmacology; D013347:Subcellular Fractions; D020798:Two-Hybrid System Techniques
chemical_list: C505032:CFTR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D013267:Stilbenes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex