Regulation of the Fanconi anemia group C protein through proteolytic modification

被引:12
作者
Brodeur, I
Goulet, I
Tremblay, CS
Charbonneau, C
Delisle, MC
Godin, C
Huard, C
Khandjian, EW
Buchwald, M
Levesque, G
Carreau, M [1 ]
机构
[1] CHUQ PAvillon St Francois Assise, Unite Genet Humaine & Mol, Quebec City, PQ G1L 3L5, Canada
[2] Univ Laval, Dept Pediat, Quebec City, PQ G1K 7P4, Canada
[3] Univ Laval, Dept Med Biol, Quebec City, PQ G1K 7P4, Canada
[4] Hosp Sick Children, Res Inst, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada
[5] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1A8, Canada
基金
加拿大健康研究院;
关键词
D O I
10.1074/jbc.M301291200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4713 / 4720
页数:8
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