title: Fanconi anemia proteins interact with CtBP1 and modulate the expression of the Wnt antagonist Dickkopf-1.
abstract: Fanconi anemia (FA) is a genetic disorder characterized by congenital abnormalities, bone marrow failure, and increased susceptibility to cancer. Of the fifteen FA proteins, Fanconi anemia group C (FANCC) is one of eight FA core complex components of the FA pathway. Unlike other FA core complex proteins, FANCC is mainly localized in the cytoplasm, where it is thought to function in apoptosis, redox regulation, cytokine signaling, and other processes. Previously, we showed that regulation of FANCC involved proteolytic processing during apoptosis. To elucidate the biological significance of this proteolytic modification, we searched for molecular interacting partners of proteolytic FANCC fragments. Among the candidates obtained, the transcriptional corepressor protein C-terminal binding protein-1 (CtBP1) interacted directly with FANCC and other FA core complex proteins. Although not required for stability of the FA core complex or ubiquitin ligase activity, CtBP1 is essential for proliferation, cell survival, and maintenance of chromosomal integrity. Expression profiling of CtBP1-depleted and FA-depleted cells revealed that several genes were commonly up- and down-regulated, including the Wnt antagonist Dickkopf-1 (DKK1). These findings suggest that FA and Wnt signaling via CtBP1 could share common effectors.
authors.affiliation: Centre hospitalier universitaire de Québec Research Center, Québec, QC, Canada.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Huard
authors.forename: Cédric S
authors.initials: CS
authors.lastname: Tremblay
authors.forename: Kathrin
authors.initials: K
authors.lastname: Helsper
authors.forename: Marie-Chantal
authors.initials: MC
authors.lastname: Delisle
authors.forename: Detlev
authors.initials: D
authors.lastname: Schindler
authors.forename: Georges
authors.initials: G
authors.lastname: Lévesque
authors.forename: Madeleine
authors.initials: M
authors.lastname: Carreau
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D043171:Chromosomal Instability; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D051856:Fanconi Anemia Complementation Group Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*
chemical_list: D015415:Biomarkers; C501126:DKK1 protein, human; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein