The Fanconi anemia group C protein interacts with uncoordinated 5A and delays apoptosis.

TitleThe Fanconi anemia group C protein interacts with uncoordinated 5A and delays apoptosis.
Publication TypeJournal Article
Year of Publication2014
AuteursHuang, FF, Ben Aissa, M, Magron, A, Huard, CC, Godin, C, Lévesque, G, Carreau, M
JournalPLoS One
Volume9
Issue3
Paginatione92811
Date Published2014
ISSN1932-6203
KeywordsApoptosis, Carrier Proteins, Cell Line, Cytoplasm, Fanconi Anemia Complementation Group C Protein, Humans, Models, Biological, Protein Binding, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Protein Transport, Receptors, Cell Surface, Two-Hybrid System Techniques
Abstract

The Fanconi anemia group C protein (FANCC) is one of the several proteins that comprise the Fanconi anemia (FA) network involved in genomic surveillance. FANCC is mainly cytoplasmic and has many functions, including apoptosis suppression through caspase-mediated proteolytic processing. Here, we examined the role of FANCC proteolytic fragments by identifying their binding partners. We performed a yeast two-hybrid screen with caspase-mediated FANCC cleavage products and identified the dependence receptor uncoordinated-5A (UNC5A) protein. Here, we show that FANCC physically interacts with UNC5A, a pro-apoptotic dependence receptor. FANCC interaction occurs through the UNC5A intracellular domain, specifically via its death domain. FANCC modulates cell sensitivity to UNC5A-mediated apoptosis; we observed reduced UNC5A-mediated apoptosis in the presence of FANCC and increased apoptosis in FANCC-depleted cells. Our results show that FANCC interferes with UNC5A's functions in apoptosis and suggest that FANCC may participate in developmental processes through association with the dependence receptor UNC5A.

DOI10.1371/journal.pone.0092811
Alternate JournalPLoS ONE
PubMed ID24676280
PubMed Central IDPMC3968024
Grant List / / Canadian Institutes of Health Research / Canada