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Published on: February 9, 2024
The Fanconi anemia group C protein interacts with uncoordinated 5A and delays apoptosis
FengFei Huang1, Manel Ben Aissa1, Audrey Magron1
1Department of Pediatrics, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
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.
Insights
Fanconi anemia group C protein (FANCC) interacts with the pro-apoptotic receptor UNC5A. FANCC suppresses UNC5A-induced apoptosis, suggesting a role in development.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Fanconi anemia group C protein (FANCC) is crucial for genomic stability within the Fanconi anemia (FA) network.
- FANCC regulates apoptosis via caspase-mediated processing, primarily functioning in the cytoplasm.
Purpose of the Study:
- To investigate the function of FANCC proteolytic fragments by identifying their binding partners.
- To elucidate the interaction between FANCC and its cleavage products in the context of apoptosis regulation.
Main Methods:
- Yeast two-hybrid screening was employed using caspase-mediated FANCC cleavage products.
- Co-immunoprecipitation and apoptosis assays were utilized to validate interactions and functional consequences.
Main Results:
- The dependence receptor uncoordinated-5A (UNC5A) was identified as a binding partner for FANCC fragments.
- FANCC physically interacts with the intracellular death domain of UNC5A.
- FANCC presence reduces UNC5A-mediated apoptosis, while FANCC depletion enhances it.
Conclusions:
- FANCC interferes with the pro-apoptotic functions of UNC5A.
- The interaction between FANCC and UNC5A suggests a novel role for FANCC in modulating apoptosis and potentially in developmental processes.
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