Programmed cell death (apoptosis) is a highly conserved, gene-directed process that is normally required during animal development and also established in the pathology and treatment of some human diseases. We are examining the mechanisms that regulate the activity of Reaper (rpr) an essential cell death gene in Drosophila. We recently obtained evidence that Rpr associates with the p35 protein, a virally-encoded negative regulator of apoptosis, which functions in worms, insects and mammals. We also found that induction of p35 expression can block Rpr-mediated apoptosis in cultured Drosophila cells. These observations prompted us to hypothesize that p35 may directly bind and thereby inhibit Rpr function. I propose to test this hypothesis by examining whether Rpr interacts p35 in vivo, and whether p35 can directly bind Rpr. If the hypothesis is proven correct, I will utilize the yeast two-hybrid screen method to search for a Drosophila form of p35 and mammalian homologs of Rpr. These studies should provide fundamental insights into mechanisms of apoptosis and might provide novel rationales for treatments of various human diseases.
