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.
Highlights
The Fanconi anemia group C protein (FANCC) is a multifunctional protein, with roles in several cellular processes, such as DNA damage signaling, redox regulation, transcriptional regulation, and apoptosis [1]
Among the positive yeast colonies that were obtained with FANCC1-306, two independent and strong positive candidates encoded the Cterminal portion of the uncoordinated-5 A (UNC5A) protein
Eight of the eleven clones that were retested in yeasts assays, including UNC5A, showed positive interaction with FANCC1-306, whereas three candidates did not show interaction with FANCC1-306 when plated on selective media (-TLHA)
Summary
The Fanconi anemia group C protein (FANCC) is a multifunctional protein, with roles in several cellular processes, such as DNA damage signaling, redox regulation, transcriptional regulation, and apoptosis [1]. Mutations in the FANCC gene lead to Fanconi anemia, a genetic disease characterized by a progressive depletion of bone marrow cells [2,3]. This disease is associated with various congenital malformations and an increased risk of malignancies [4]. FANCC is the cytoplasmic component of the FA pathway, and in association with the Fanconi anemia group E (FANCE) protein, translocates to the nucleus in response to crosslink damage [8,9,10]. One candidate coded for the dependence receptor uncoordinated-5 A (UNC5A)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
