Yeast RAS genes.
Yeast RAS genes.
复制标题
酵母 RAS 基因。
DOI：
10.1016/0304-419x(88)90002-9
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Tamanoi,F
中科院分区：
文献类型：
--
作者：
Tamanoi,F
0304- 419 X/88/$03.50© 1988 Elsevier Science Pubfishers BV（生物医学部）肉瘤病毒似乎在人类肿瘤形成中起重要作用。用来自多种人类肿瘤的DNA转染NIH 3 T3细胞，已导致转化基因的检测，其中大多数已被证明与ras癌基因相关（综述见参考文献2）。此外，在40%的人结肠和直肠肿瘤中检测到ras基因的突变形式[3，4]。这些突变的ras基因包含一个单一的碱基改变，从他们的正常对应物，这导致一个单一的氨基酸变化，在他们的基因产物。ras基因的产物是21 kDa的蛋白质，称为p21，其定位于质膜中[5，6]。p21表现出结合鸟嘌呤核苷酸以及水解GTP的生物化学活性[7-11]。基于致癌突变体产生的某些蛋白质中GT3活性受损的发现，假设ras基因产物参与跨膜信号转导过程[12，13]。酵母作为研究ras基因功能的模型系统的潜在用途已经通过在酿酒酵母中发现与哺乳动物ras基因高度同源的两个基因RAS 1和RAS 2而实现[14，15]。在过去的4年中，人们对酵母RAS 1和RAS 2基因的功能研究取得了很大进展，但由于酵母基因的功能研究还不成熟，因此酵母RAS 1和RAS 2基因的功能研究还有待进一步深入。已经清楚的是，酵母RAS 2基因参与环AMP（cAMP）产生的调节[16]。此外，最近的一份报告表明RAS 1基因参与了肌醇磷脂周转（PI周转）的调节[17]。因此，酵母基因似乎参与了第二信使形成的调节。此外，研究酵母中的RAS基因提供了一个新的机会，以了解一般的ras蛋白的生物合成。ras蛋白作为前体在胞质溶胶中产生，经历涉及脂肪酸酰化的翻译后修饰，并定位于质膜中[5，6，18，19]。如何
0304-419X/88/$03.50© 1988 Elsevier Science Pubfishers BV (Biomedical Division) sarcoma viruses, appear to play an important role in human tumor formation. Transfection of NIH3T3 cells with DNAs from a variety of human tumors has resulted in the detection of transforming genes, most of which have been shown to be related to the ras oncogenes (reviewed in Ref. 2). Furthermore, mutated forms of the ras gene have been detected in 40% of human colon and rectal tumors [3, 4]. These mutant ras genes contain a single base alteration from their normal counterparts, which results in a single amino-acid change in their gene products. Products of the ras genes are 21 kDa proteins, termed p21, which are localized in the plasma membrane [5, 6]. The p21 exhibits biochemical activity to bind guanine nucleotides as well as to hydrolyze GTP [7-11]. Based on the finding that the GTPase activity is impaired in some of the proteins produced by the oncogenic mutants, it is hypothesized that the ras-gene products are involved in the process of signal transduction across the membrane [12, 13]. The potential use of yeast as a model system to investigate the function of the ras genes has been realized by the discovery of two genes in Saccharomyces cerevisiae, RAS1 and RAS2, highly homologous to the mammalian ras genes [14, 15]. Because powerful yeast genetics could be employed to study the function of these genes, it was expected that the function of the yeast genes could be rapidly elucidated and that this knowledge might shed light on the function of the mammalian genes.During the past 4 years, much progress has been made in understanding the function of the yeast RAS1 and RAS2 genes. It has become clear that the yeast RAS2 gene is involved in the regulation of cyclic AMP (cAMP) production [16]. Furthermore, a recent report has implicated the RAS1 gene in the regulation of inositol phospholipids turnover (PI turnover)[17]. Thus, the yeast genes seem to be involved in the regulation of second messenger formation. In addition, investigation of the RAS genes in yeast has provided a novel opportunity to understand the biosynthesis of ras proteins in general. The ras proteins are produced as precursors in cytosol, undergo posttranslational modifications which involve fatty-acid acylation, and are localized in the plasma membrane [5, 6, 18, 19]. How the