| The study of the eukaryotic cell division cycle has led to the identification and cloning of a master set of control machinery governing normal cell growth and division that is conserved from yeast to man: the cyclin-dependent kinases (CDKs). My projects have primarily focused on the identification and characterization of novel regulators of CDKs in mammalian cells through the use of immunological techniques and bioinformatics tools. I began with a study of negative regulators of CDKs: CDK inhibitors. I identified three members of the p16 family of CDK inhibitors, and characterized their protein-protein interactions. I also worked on characterization of another CDK inhibitor, p21. Turning to a study of cell cycle complexes in the human factor-dependent leukemia cell line TF-1, I identified a novel Bcl-2-regulated cyclin B1-CDC2-associated protein p37. Through database searching and sequence analysis, I identified two novel cyclins: cyclin L1 and cyclin L2, which I attempted to further characterize. And, also using bioinformatics tools, I identified 25 potential ubiquitin-conjugating enzymes, part of the ubiquitin-mediated proteolysis system, which regulates the expression of several CDK-regulatory proteins. |
