Lovastatin blocks N-ras oncogene-induced neuronal differentiation

CE Mendola, JM Backer - Cell Growth Differ, 1990 - AACR
CE Mendola, JM Backer
Cell Growth Differ, 1990AACR
Abstract ras p21 must be posttranslationally processed in order to be localized to the inner
plasma membrane. The first obligatory processing step is the farnesylation of ras p21.
Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, may
prevent the farnesylation of de novo synthesized ras p21. We demonstrate that N-ras
oncogene-induced neuronal differentiation of UR61J rat pheochromocytoma cells is blocked
by lovastatin. Our data show that this effect is due to the inhibition of ras p21 farnesylation …
Abstract
ras p21 must be posttranslationally processed in order to be localized to the inner plasma membrane. The first obligatory processing step is the farnesylation of ras p21. Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, may prevent the farnesylation of de novo synthesized ras p21. We demonstrate that N-ras oncogene-induced neuronal differentiation of UR61J rat pheochromocytoma cells is blocked by lovastatin. Our data show that this effect is due to the inhibition of ras p21 farnesylation. The results suggest that ras oncogene-induced phenotype in mammalian cells may be eliminated by preventing the proper processing of ras p21.
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