Geranylgeranyl as Well as Farnesyl Moiety Is Transferred to Ras p21 Overproduced in Adrenocortical Cells Transformed by c-Ha-rasEJOncogene

Autor: Osman, Hanan, Mazet, Jean-Luc, Maume, Gabrielle, Maume, Bernard F.
Zdroj: Biochemical and Biophysical Research Communications; February 1997, Vol. 231 Issue: 3 p789-792, 4p
Abstrakt: Theras-transformed newborn rat adrenocortical (RTAC) cells were obtained by transfection with the mutated c-Ha-rasEJoncogene. They are proliferative and tumorigenic cells characterized by expression of the c-Ha-rasEJoncogene and overexpression of a wild-typerasoncogene. The overproduced Ras p21 was identified here as Ki-Ras p21 by western blotting using a specific anti-Ki-Ras monoclonal antibody. Radioactivity derived from [14C]mevalonolactone was strongly incorporated into Ras p21 overproduced in RTAC cells. RTAC cells pretreated with lovastatin and labeled with either [3H]geranylgeranyl-pyrophosphate or [3H]farnesyl-pyrophosphate incorporated also radioactivity into Ras p21. These results showed that overproduced Ras proteins were geranylgeranylated as well as farnesylated in RTAC cells. These findings suggest that the strategy for inhibiting proliferation of Ki-ras-dependent tumorigenic cells should be directed against not only farnesylation but also geranylgeranylation of Ras p21.
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