GERANYLGERANYL AS WELL AS FARNESYL MOIETY IS TRANSFERRED TO RAS P21 OVERPRODUCED IN ADRENOCORTICAL-CELLS TRANSFORMED BY C-HA-RAS(EJ) ONCOGENE

The ras-transformed newborn rat adrenocortical (RTAC) cells were obtai ned by transfection with the mutated c-Ha-ras(EJ) oncogene. They are p roliferative and tumorigenic cells characterized by expression of the c-Ha-ras(EJ) oncogene and overexpression of a wildtype ras oncogene. T he overproduced Ras p21 was identified here as Ki-Ras p21 by western b lotting using a specific anti-Ki-Ras monoclonal antibody. Radioactivit y derived from [C-14]mevalonolactone was strongly incorporated into Ra s p21 overproduced in RTAC cells. RTAC cells pretreated with lovastati n and labeled with either [H-3] geranylgeranyl-pyrophosphate or [H-3]f arnesyl-pyrophosphate incorporated also radioactivity into Ras p21. Th ese results showed that overproduced Ras proteins were geranylgeranyla ted as well as farnesylated in RTAC cells. These findings suggest that the strategy for inhibiting proliferation of Ki-ras-dependent tumorig enic cells should be directed against not only farnesylation but also geranylgeranylation of Ras p21. (C) 1997 Academic Press.