Exploring the Function of the Fanconi Anemia Proteins FANCA, FANCC and FANCG Through Protein-protein Interactions
Indiana University, 2008 - 163 pages
Fanconi anemia (FA) is a rare autosomal recessive disease that is characterized by aplastic anemia, congenital abnormalities, birth defects and increased susceptibility to cancer. There are thirteen complementation groups for FA including FA-A, FA-B, FA-C, FA-D1, FA-D2, FA-E, FA-F, FA-G, FA-I, FA-J, FA-L, FA-M, and FA-N. We used Tandem Affinity Purification to determining proteins that interact with the FA proteins, FANCA, FANCC and FANCG. Several proteins were identified by mass spectrometry to interact with FANCA, FANCC and/or FANCG. An interaction between FANCA and Huntingtin was found under DNA damage induced conditions, and was confirmed by immunoprecipitation. In addition, an interaction between FANCC and procaspase-8 was also confirmed by immunoprecipitation. The function of the interaction between FANCC and procaspase-8 was explored through additional experiments to study the implied link between FANCC and apoptosis. We found that there are differences in proteins found in the mitochondrial pathway and death receptor pathway when comparing wild type (+/+) to fancc (-/-) mouse embryonic fibroblasts (MEFs), which could be due to the lack of the Fancc/procaspase-8 interaction. Additional experiments are needed to clarify the role of FANCC in apoptosis. Several hypothesis and experiments, that could further the understanding of FA through the study of protein interactions can be generated from these results.
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