Research Project
6457298
DESCRIPTION (provided by applicant): The amount of any given protein in a cell is determined by the rate of its synthesis and the rate of its degradation or proteolysis. Some proteins in the cell are degraded rapidly, while others have relatively long half-lives. In some cases, the rate of degradation of a particular protein can change dramatically depending on the circumstances. The main goal of the research proposed here is to understand the role of proteolysis in early embryogenesis in C. elegans. By learning about key proteins in this process the principal investigator hopes to better understand the pathway that leads to selective proteins destruction. A major route for protein degradation in the cell is the ubiquitin-proteasome pathway. Proteins are targeted for destruction by the addition of multiple ubiquitin molecules. These multi-ubiquitinated proteins are then degraded by the proteasome, a large protein complex with protease activity. The approach to understanding the process of regulated proteolysis starts with identifying genes involved in the ubiquitin-proteasome pathway in the available genome sequence for C. elegans. The function and localization of the proteins encoded by these genes will be then analyzed. RNA interference (RNAi) is being used to determine the loss of function of phenotype in the embryo. For localization studies, GFP fusion proteins will be made and expressed in early embryos. Thus, important information can be obtained on the function and subcellular localization of the components of the ubiquitin-proteasome pathway. In the future, it may be possible to predict the degradative pathway for a given protein based on its sequence or its interaction with a given E3 ligase. The proposed studies are a step towards this level of understanding.
