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Science 7 September 1990:
Vol. 249. no. 4973, pp. 1133 - 1139
DOI: 10.1126/science.2204115
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Articles

Science, Vol 249, Issue 4973, 1133-1139
Copyright © 1990 by American Association for the Advancement of Science

articles

Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein

WR Schafer, CE Trueblood, CC Yang, MP Mayer, S Rosenberg, CD Poulter, SH Kim, and J Rine

Department of Molecular and Cell Biology, University of California, Berkeley 94720.

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.


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