The broad goal of the proposed research is to understand a novel cell communication pathway used in animal development. This cell communication pathway is regulated in a unique manner by ubiquitin- mediated proteolysis. Thus, the proposed research also provide important new information about ubiquitin pathway function and about how ubiquitin regulates development. The specific research proposed aims to identify and understand the interactions of the proteins that constitute the novel cell communication pathway used during Drosophila eye development defined by the fat facets (faf) gene. The faf gene encodes a deubiquitinating enzyme, or UBP, that regulates the ubiquitin-mediated proteolysis of specific proteins. In the absence of FAF protein, an unknown neural inhibition pathway fails to function, resulting in disorganized retinas containing many ectopic photoreceptors. Genetic screens will be used to identify the genes encoding the components of the cell communication pathway. Molecular cloning and transgenic fly technology will be used to isolate the genes and study the functions of the proteins they encode. These techniques will also be used to perform a structure/function analysis of the FAF protein. As mouse and human faf homologs have been identified, the cell communication pathway regulated by faf is likely to be used universally in animal development. Ubiquitin-mediated proteolysis regulates cell growth and some UBPs are oncogenes. Although ubiquitination may be used as widely as phosphorylation in regulating protein function, very little is known about the role of the ubiquitin pathway or UBPs in multicellular organisms. Drosophila faf mutants provide us with a unique opportunity to investigate a relatively unknown biochemical pathway in a powerful genetic system.
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