SPECIFIC LABELING OF ISOPRENYLATED PROTEINS - APPLICATION TO STUDY INHIBITORS OF THE POSTTRANSLATIONAL FARNESYLATION AND GERANYLGERANYLATION

Specific labeling of either farnesylated or geranylgeranylated protein s in human PC-3 prostate cancer cell line was obtained by suppression of mevalonic acid biosynthesis with lovastatin, 50 mu M,followed by su pplementation of cell culture medium with either [H-3]farnesyl- or [H- 3]geranylgeranyl-pyrophosphate. The immunoprecipitation of either a fa rnesylated (p21 ras) or geranylgeranylated (p21 rap 1) protein demonst rated that labeling was specific since proteins were detected only if the appropriate isoprenoid was added to the culture medium. TLC analys is indicated that no conversion of one isoprenoid to the other occurre d in these conditions. The selective labeling of either farnesylated o r geranylgeranylated proteins may be a valuable tool for the developme nt of inhibitors of isoprenoid transferases as a potential new class o f antitumor agents. (C) 1995 Academic Press, Inc.