Proteasomes are large, multi-subunit complexes that act as the proteolytic core of the ubiquitin-dependent protein degrading machinery, and are responsible for the removal of abnormal polypeptides and short lived regulatory proteins from eukaryotic cells. Recent work, using the tools of biochemistry and cell biology, has revealed much about the physical and biochemical properties of proteasomes, but many aspects of their biological function remain unclear. As an approach toward learning more about the role of proteasome-mediated proteolysis during metazoan development, my lab has initiated a genetic and molecular study of Drosophila proteasomes. Our work is focused on two major questions: What is the role of the ubiquitin-proteasome pathway in specific developmental processes? Are there structurally distinct cell-type specific proteasomes that have specialized functions? To address the first question we have taken a mutational approach. We have isolated and characterized two dominant temperature-sensitive proteasome mutants (DTS5 and DTS7) that can be used to disrupt proteasome function in vivo, and are using them to examine their effects on specific biological processes. For the second question, we have used a reverse genetics approach. We have identified and characterized five proteasome subunit genes that are expressed exclusively in the male germline. A combination of molecular, cell biological, and genetic approaches are being used to investigate the importance of proteasome-mediated protein degradation in spermatogenesis, and to address the functional role of the testes-specific subunits in this process.