Analysis of Morgue, a novel ubiquitination protein that functions in programmed cell death

The Drosophila morgue gene was identified as a regulator of programmed cell death and protein ubiquitination. It has been shown to enhance programmed cell death via promoting the turnover of DIAP1, a conserved anti-apoptotic protein. Morgue protein contains a zinc finger motif, an F box domain and a ubiquitin E2 conjugase variant domain with a Cysteine to Glycine substitution at the catalytic site. This unique domain/motif architecture suggests that Morgue may have very distinctive activities. However, how and what each domain/motif contributes to Morgue function remains unexplored. My dissertation project focused on a study of Morgue protein evolution and function using a combination of bioinformatics, genetics and biochemical methods. The results suggest that Morgue exhibits widespread but restricted phylogenetic distribution among invertebrate metazoans; the study of Morgue's origin provides an example of how multi-domain proteins may evolve. Results of functional studies revealed that over-expression of Morgue can induce a homozygous lethal phenotype that is independent of either F-box or the Glycine in the UEV domain. In addition, co-immunoprecipitation experiments have shown that Morgue associates with SkpA and Lys48 linked polyubiquitin chains, indicating that Morgue might be a multi-functional protein in PCD and ubiquitination.