The broader goals of the proposed work are aimed at the development of chemical approaches to the study of cell division and ultimately cancer. More specifically, the developing field of 'chemical genetics' will be applied to the understanding of cell cycle regulators and the mitotic spindle checkpoint. The King laboratory has identified several compounds that block exit from mitosis and inhibit cyclin proteolysis. The goals of the proposed research are to identify the biochemical targets of these compounds and pursue the mechanism of how these compounds inhibit cyclin proteolysis. Additionally, we propose to develop a new strategy that will enable the rapid identification of protein targets of active compounds found in chemical genetic screens.
| Tochtrop, Gregory P; King, Randall W (2004) Target identification strategies in chemical genetics. Comb Chem High Throughput Screen 7:677-88 |
| Verma, Rati; Peters, Noel R; D'Onofrio, Mariapina et al. (2004) Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain. Science 306:117-20 |
