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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM018069-03
Application #
2684633
Study Section
Biochemistry Study Section (BIO)
Project Start
1998-04-01
Project End
Budget Start
1998-04-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Duke University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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