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Date of Award
5-2012
Access Type
Campus Access
Document type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Neuroscience and Behavior
First Advisor
John R. Nambu
Second Advisor
Elizabeth A. Connor
Third Advisor
Lawrence M. Schwartz
Subject Categories
Cell Biology | Genetics | Molecular Biology
Abstract
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.
DOI
https://doi.org/10.7275/5691853
Recommended Citation
Zhou, Ying, "Analysis Of Morgue, A Novel Ubiquitination Protein That Functions In Programmed Cell Death" (2012). Doctoral Dissertations 1896 - February 2014. 372.
https://doi.org/10.7275/5691853
https://scholarworks.umass.edu/dissertations_1/372