title: The Fanconi anemia group C protein interacts with uncoordinated 5A and delays apoptosis.
abstract: The Fanconi anemia group C protein (FANCC) is one of the several proteins that comprise the Fanconi anemia (FA) network involved in genomic surveillance. FANCC is mainly cytoplasmic and has many functions, including apoptosis suppression through caspase-mediated proteolytic processing. Here, we examined the role of FANCC proteolytic fragments by identifying their binding partners. We performed a yeast two-hybrid screen with caspase-mediated FANCC cleavage products and identified the dependence receptor uncoordinated-5A (UNC5A) protein. Here, we show that FANCC physically interacts with UNC5A, a pro-apoptotic dependence receptor. FANCC interaction occurs through the UNC5A intracellular domain, specifically via its death domain. FANCC modulates cell sensitivity to UNC5A-mediated apoptosis; we observed reduced UNC5A-mediated apoptosis in the presence of FANCC and increased apoptosis in FANCC-depleted cells. Our results show that FANCC interferes with UNC5A's functions in apoptosis and suggest that FANCC may participate in developmental processes through association with the dependence receptor UNC5A.
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
authors.forename: FengFei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
authors.forename: Manel
authors.initials: M
authors.lastname: Ben Aissa
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Magron
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Huard
authors.affiliation: Department of Psychiatry and Neurosciences, Université Laval, Cité Universitaire, Québec, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Godin
authors.affiliation: Department of Psychiatry and Neurosciences, Université Laval, Cité Universitaire, Québec, Canada.
authors.forename: Georges
authors.initials: G
authors.lastname: Lévesque
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Carreau
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm; D052218:Fanconi Anemia Complementation Group C Protein / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D000075386:Netrin Receptors; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D052218:Fanconi Anemia Complementation Group C Protein; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; C000603585:UNC5A protein, human