Regulation of the Fanconi anemia group C protein through proteolytic modification.
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.
Brodeur
Isabelle
I
Unité de Génétique Humaine et Moléculaire, CHUQ-Pavillon St-François d'Assise, Quebec, Quebec G1L 3L5, Canada.
Goulet
Isabelle
I
Tremblay
Cédric S
CS
Charbonneau
Chantal
C
Delisle
Marie-Chantal
MC
Godin
Chantal
C
Huard
Caroline
C
Khandjian
Edward W
EW
Buchwald
Manuel
M
Lévesque
Georges
G
Carreau
Madeleine
M
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
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