Regulation of the Fanconi Anemia Group C Protein through Proteolytic Modification

Isabelle Brodeur, Isabelle Goulet, Cédric S. Tremblay, Chantal Charbonneau, Marie Chantal Delisle, Chantal Godin, Caroline Huard, Edward W. Khandjian, Manuel Buchwald, Georges Lévesque, Madeleine Carreau

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4713-4720
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number6
DOIs
Publication statusPublished - 6 Feb 2004

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