« Previous AbstractThe nature and development of sex attractant specificity in cockroaches of the genus Periplaneta. IV. electrophysiological study of attractant specificity and its determination by juvenile hormone    Next AbstractEnzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein »

Science

Title:		Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans
Author(s):		Schafer WR; Kim R; Sterne R; Thorner J; Kim SH; Rine J;
Address:		"Department of Biochemistry, University of California, Berkeley 94720"
Journal Title:		Science
Year:		1989
Volume:		245
Issue:		4916
Page Number:		379 - 385
DOI:		10.1126/science.2569235
ISSN/ISBN:		0036-8075 (Print) 0036-8075 (Linking)
Abstract:		"The activity of an oncoprotein and the secretion of a pheromone can be affected by an unusual protein modification. Specifically, posttranslational modification of yeast a-factor and Ras protein requires an intermediate of the cholesterol biosynthetic pathway. This modification is apparently essential for biological activity. Studies of yeast mutants blocked in sterol biosynthesis demonstrated that the membrane association and biological activation of the yeast Ras2 protein require mevalonate, a precursor of sterols and other isoprenes such as farnesyl pyrophosphate. Furthermore, drugs that inhibit mevalonate biosynthesis blocked the in vivo action of oncogenic derivatives of human Ras protein in the Xenopus oocyte assay. The same drugs and mutations also prevented the posttranslational processing and secretion of yeast a-factor, a peptide that is farnesylated. Thus, the mevalonate requirement for Ras activation may indicate that attachment of a mevalonate-derived (isoprenoid) moiety to Ras proteins is necessary for membrane association and biological function. These observations establish a connection between the cholesterol biosynthetic pathway and transformation by the ras oncogene and offer a novel pharmacological approach to investigating, and possibly controlling, ras-mediated malignant transformations"
Keywords:		"Amino Acid Sequence Animals Cells, Cultured Drosophila Electrophoresis, Polyacrylamide Gel Fungal Proteins/genetics/*metabolism *Genes, ras Humans Hydroxymethylglutaryl CoA Reductases/genetics Hydroxymethylglutaryl-CoA Synthase/genetics Immunoblotting Mat;"
Notes:		"MedlineSchafer, W R Kim, R Sterne, R Thorner, J Kim, S H Rine, J eng CA-45593/CA/NCI NIH HHS/ GM21841/GM/NIGMS NIH HHS/ GM31105/GM/NIGMS NIH HHS/ etc. Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. 1989/07/28 Science. 1989 Jul 28; 245(4916):379-85. doi: 10.1126/science.2569235"