title: The Fanconi Anemia C Protein Binds to and Regulates Stathmin-1 Phosphorylation.
abstract: The Fanconi anemia (FA) proteins are involved in a signaling network that assures the safeguard of chromosomes. To understand the function of FA proteins in cellular division events, we investigated the interaction between Stathmin-1 (STMN1) and the FA group C (FANCC) protein. STMN1 is a ubiquitous cytosolic protein that regulates microtubule dynamics. STMN1 activities are regulated through phosphorylation-dephosphorylation mechanisms that control assembly of the mitotic spindle, and dysregulation of STMN1 phosphorylation is associated with mitotic aberrancies leading to chromosome instability and cancer progression. Using different biochemical approaches, we showed that FANCC interacts and co-localizes with STMN1 at centrosomes during mitosis. We also showed that FANCC is required for STMN1 phosphorylation, as mutations in FANCC reduced serine 16- and 38-phosphorylated forms of STMN1. Phosphorylation of STMN1 at serine 16 is likely an event dependent on a functional FA pathway, as it is reduced in FANCA- and FANCD2-mutant cells. Furthermore, FA-mutant cells exhibited mitotic spindle anomalies such as supernumerary centrosomes and shorter mitotic spindles. These results suggest that FA proteins participate in the regulation of cellular division via the microtubule-associated protein STMN1.
authors.affiliation: CHU de Québec, CHUL Research Center, Québec, QC, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Magron
authors.affiliation: Department of Pediatrics, Université Laval, Québec, QC, Canada; CHU de Québec, CHUL Research Center, Québec, QC, Canada.
authors.forename: Sabine
authors.initials: S
authors.lastname: Elowe
authors.affiliation: Department of Pediatrics, Université Laval, Québec, QC, Canada; CHU de Québec, CHUL Research Center, Québec, QC, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Carreau
mesh_terms: D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism*; D052218:Fanconi Anemia Complementation Group C Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D050777:Stathmin / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D052218:Fanconi Anemia Complementation Group C Protein; C493995:STMN1 protein, human; D050777:Stathmin