GOEBL 9728069 The long range goal of this project is to understand how a complex of proteins called the SPC or S-phase promoting complex controls the G1 to S phase transition of the yeast cell cycle. SPC includes Cdc34p, a ubiquitin-conjugating enzyme that can target protein substrates for degredation via a large protease known as proteasome. A number of laboratories have uncovered potential Cdc34p substrates, including activators of the CDC 28 protein kinase (Cln1p, Cln2p, Cln3p) as well as Cdc28p inhibitors (Far1p and Sic1p). However, the mechanisms by which SPC selects these proteins as substrates and the manner in which the enzymatic activity of Cdc34p is regulated is not clear. The identification in higher cells of counterparts to both Cdc34p and Cdc35p suggests related mechanisms regulate cell cycle progression in higher cells. This project will involve the biochemical characterization of proteins that interact with known components of the SPC. A number of candidate proteins have been uncovered by genetic means and the encoding genes will also be characterized further to understand their role in SPC function. An understanding of how yeast control the G1 to S phase transition will provide insight into how higher cells regulate the decision to enter S phase during proliferative phases as well as arrest proliferation during differentiation or cellular stress. Understanding how cells make the decision to divide or to undergo development into specific tissues are key questions important for many fields ranging from cancer biology to bacterial resistance in plants. This project examines a number of the factors known to control protein function by tagging the proteins for rapid breakdown and removing them from the cell. It will lead to a greater understanding of how cells control protein breakdown to regulate a wide range of cellular activities. It is a highly irreversible process that is used by the cell to control a large number of different signaling events. Protein breakdown is critical for allowing both plants and animal cells to respond to changes in their environments.
