Schafer W R, Trueblood C E, Yang C C, Mayer M P, Rosenberg S, Poulter C D, Kim S H, Rine J
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Science. 1990 Sep 7;249(4973):1133-9. doi: 10.1126/science.2204115.
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.
酵母α-交配信息素前体、Ras蛋白、核纤层蛋白以及三聚体G蛋白的某些亚基的翻译后加工，需要在其羧基末端进行一系列复杂修饰。这种加工包括三个步骤：半胱氨酸残基的异戊二烯化、蛋白水解加工和羧甲基化。在酿酒酵母中，DPR1-RAM1基因的产物参与此类加工。通过使用以假定的α-交配信息素前体为模型的肽底物进行体外测定，发现DPR1-RAM1中的突变会导致异戊二烯化反应缺陷。进一步表明，DPR1-RAM1编码一种蛋白质异戊二烯基转移酶的必需且有限的组分。这些研究还暗示了异戊二烯化蛋白共有的三个加工步骤的固定顺序：异戊二烯化、蛋白水解，然后是羧甲基化。由于酵母蛋白异戊二烯基转移酶也可以使人类H-ras p21前体异戊二烯化，因此人类DPR1-RAM1类似物可能是抗癌化疗的有用靶点。
