CK1delta/epsilon Inhibits Apoptosis in Drosophila

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DESCRIPTION (provided by applicant): Apoptosis, or programmed cell death, is critical for development and maintenance of tissue homeostasis. Important negative regulators of caspase activity are a family of proteins called inhibitors of apoptosis (IAP). A well characterized Drosophila IAP, DIAP1, is critical for inhibition of apoptosis. DIAP1 is regulated by a group of proteins, called IAP regulatory proteins that bind to and inhibit its activity. Well-characterized Drosophila members of the IAP regulatory proteins include Reaper, Hid and Grim. The Cadigan lab has carried out a genetic screen and identified discs overgrown (dco), a Drosophila homologue of casein kinase-delta/epsilon, as an inhibitor of hid-dependent apoptosis when overexpressed. Consistent with its overexpression phenotype, loss of dco in the wing imaginal disc resulted in elevated levels of apoptosis and decreased levels of DIAP1 protein. We hypothesize that Dco either inhibits Hid and/or activates DIAP1 to inhibit apoptosis. I will utilize cell culture and in vitro biochemical analysis to determine whether Dco interacts directly with Hid or DIAP1. In addition, I will use genetic approaches to identify additional genes that are involved in dco-dependent inhibition of apoptosis.