Publication Date:
1990-09-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schafer, W R -- Trueblood, C E -- Yang, C C -- Mayer, M P -- Rosenberg, S -- Poulter, C D -- Kim, S H -- Rine, J -- GM21328/GM/NIGMS NIH HHS/ -- GM25521/GM/NIGMS NIH HHS/ -- GM35827/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 7;249(4973):1133-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2204115" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Cell Compartmentation
;
Cholesterol/*metabolism
;
DNA Mutational Analysis
;
Dimethylallyltranstransferase/*metabolism
;
Fungal Proteins/metabolism
;
Genes, Fungal
;
*Hemiterpenes
;
Humans
;
In Vitro Techniques
;
Molecular Sequence Data
;
Oncogene Protein p21(ras)/*metabolism
;
Organophosphorus Compounds/metabolism
;
Peptides/*metabolism
;
Polyisoprenyl Phosphates/metabolism
;
Protein Processing, Post-Translational
;
Restriction Mapping
;
Saccharomyces cerevisiae/*physiology
;
Sesquiterpenes
;
Transferases/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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