Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein.
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.
Schafer
W R
WR
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Trueblood
C E
CE
Yang
C C
CC
Mayer
M P
MP
Rosenberg
S
S
Poulter
C D
CD
Kim
S H
SH
Rine
J
J
D000595:Amino Acid Sequence; D002451:Cell Compartmentation; D002784:Cholesterol / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004122:Dimethylallyltranstransferase / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D005800:Genes, Fungal; D045782:Hemiterpenes; D006801:Humans; D066298:In Vitro Techniques; D000072235:Mating Factor; D008969:Molecular Sequence Data; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D012717:Sesquiterpenes; D014166:Transferases / Q000378:metabolism*
D005656:Fungal Proteins; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D010455:Peptides; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004809:isopentenyl pyrophosphate; D000072235:Mating Factor; C004808:farnesyl pyrophosphate; D002784:Cholesterol; D014166:Transferases; D004122:Dimethylallyltranstransferase; D015689:Oncogene Protein p21(ras)