This proposal seeks to determine the fate of prenylcysteines a presumed degradative product of prenylproteins. One potential fate of the prenylcysteines that will be explored in depth is whether these molecules are natural substrates for P-glycoprotein, a cell surface transporter which gives rise to multidrug resistant phenotypes in cancer cells when overexpressed. In approach has been designed to detect whether prenylcysteine-containing compounds produced via degradation of prenylproteins are exported by P-glycoprotein. A second approach makes use of microinjecting radiolabeled prenylcysteine compounds and detecting export from cells. In addition a set of experiments will examine the possibility that the prenyl group is recycled by the cell in song manner. This proposed research will lead to a better understanding of prenylprotein metabolism and possibly give insight into multidrug resistance in cancers.
| Zhang, L; Tschantz, W R; Casey, P J (1997) Isolation and characterization of a prenylcysteine lyase from bovine brain. J Biol Chem 272:23354-9 |
