9506885 Belote A genetic and molecular analysis of proteasomes in Drosophila will be done. The gene, l(2)73Ai, encodes a component of the proteasome. It was originally defined by the existence of an unusual dominant temperature-sensitive lethal mutant, l(3)73Ail. The developmental consequences of loss-of-function mutant alleles of this gene will be studied. Detailed analysis of the phenotype of these mutants will be done, including examination of possible maternal effects on early embryogensis. A second gene, DTS7, which evidence suggests plays an important role in proteasome function or regulation will be cloned and characterized. Extragenic suppressors of 1(3)73Ai1 will be identified and characterized. One such suppressor of 1(3)73Ai1 has already been identified and experiments will be done to define its genetic and phenotypic properties. %%% Regulated protein degradation is important for normal cell function, playing a key role in such diverse processes as growth control, metabolic regulation, embryonic development and cell cycle progression. Targeted protein breakdown is also important for protecting cells against a variety of abnormal conditions. Thus, an understanding of how cells selectively identify unwanted proteins and target them for destruction has fundamental importance for an understanding of many areas of biology. Recent studies have shown that an essential component of intracellular proteolysis is the proteasome, a large, multi-subunit complex that acts as the proteolytic core of the ubiquitin-dependent protein degrading machinery, responsible for the removal of abnormal polypeptides and short-lived regulatory proteins from eukaryotic cells. This work, a genetic characterization of one of the components of the proteasome of Drosophila, will increase our understanding of the genetic control of this very important biological process. ***
