title: Regulation of the Fanconi anemia group C protein through proteolytic modification.
abstract: The function of the Fanconi anemia group C protein (FANCC) is still unknown, though many studies point to a role in damage response signaling. Unlike other known FA proteins, FANCC is mainly localized to the cytoplasm and is thought to act as a messenger of cellular damage rather than an effector of repair. FANCC has been shown to interact with several cytoplasmic and nuclear proteins and to delay the onset of apoptosis through redox regulation of GSTP1. We investigated the fate and function of FANCC during apoptosis. Here we show that FANCC undergoes proteolytic modification by a caspase into a predominant 47-kDa ubiquitinated protein fragment. Lack of proteolytic modification at the putative cleavage site delays apoptosis but does not affect MMC complementation. These results suggest that FANCC function is regulated through proteolytic processing.
authors: Unité de Génétique Humaine et Moléculaire, CHUQ-Pavillon St-François d'Assise, Quebec, Quebec G1L 3L5, Canada.
authors: Isabelle
authors: I
authors: Brodeur
authors: Isabelle
authors: I
authors: Goulet
authors: Cédric S
authors: CS
authors: Tremblay
authors: Chantal
authors: C
authors: Charbonneau
authors: Marie-Chantal
authors: MC
authors: Delisle
authors: Chantal
authors: C
authors: Godin
authors: Caroline
authors: C
authors: Huard
authors: Edward W
authors: EW
authors: Khandjian
authors: Manuel
authors: M
authors: Buchwald
authors: Georges
authors: G
authors: Lévesque
authors: Madeleine
authors: M
authors: Carreau
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D006367:HeLa Cells; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; D016685:Mitomycin; D020169:Caspases