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Science

Title:		Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein
Author(s):		Schafer WR; Trueblood CE; Yang CC; Mayer MP; Rosenberg S; Poulter CD; Kim SH; Rine J;
Address:		"Department of Molecular and Cell Biology, University of California, Berkeley 94720"
Journal Title:		Science
Year:		1990
Volume:		249
Issue:		4973
Page Number:		1133 - 1139
DOI:		10.1126/science.2204115
ISSN/ISBN:		0036-8075 (Print) 0036-8075 (Linking)
Abstract:		"The post-translational processing of the yeast a-mating pheromone precursor, Ras proteins, nuclear lamins, and some subunits of trimeric G proteins requires a set of complex modifications at their carboxyl termini. This processing includes three steps: prenylation of a cysteine residue, proteolytic processing, and carboxymethylation. In the yeast Saccharomyces cerevisiae, the product of the DPR1-RAM1 gene participates in this type of processing. Through the use of an in vitro assay with peptide substrates modeled after a presumptive a-mating pheromone precursor, it was discovered that mutations in DPR1-RAM1 cause a defect in the prenylation reaction. It was further shown that DPR1-RAM1 encodes an essential and limiting component of a protein prenyltransferase. These studies also implied a fixed order of the three processing steps shared by prenylated proteins: prenylation, proteolysis, then carboxymethylation. Because the yeast protein prenyltransferase could also prenylate human H-ras p21 precursor, the human DPR1-RAM1 analogue may be a useful target for anticancer chemotherapy"
Keywords:		"Amino Acid Sequence Cell Compartmentation Cholesterol/*metabolism DNA Mutational Analysis Dimethylallyltranstransferase/*metabolism Fungal Proteins/metabolism Genes, Fungal *Hemiterpenes Humans In Vitro Techniques Mating Factor Molecular Sequence Data Onc;"
Notes:		"MedlineSchafer, W R Trueblood, C E Yang, C C Mayer, M P Rosenberg, S Poulter, C D Kim, S H Rine, J eng GM21328/GM/NIGMS NIH HHS/ GM25521/GM/NIGMS NIH HHS/ GM35827/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. 1990/09/07 Science. 1990 Sep 7; 249(4973):1133-9. doi: 10.1126/science.2204115"