THE TRANSFORMING GENES OF AVIAN SARCOMA VIRUSES

本提案涉及一系列调查，旨在 阐明禽肉瘤的致癌转化机制 病毒（ASV）。 主要的努力将是进一步表征基因 以及我们最近在生物学上描述的两种新的ASV，UR 1和UR 2。 我们 计划隔离条件（ts）和无条件部分删除（ptd） 突变体为了获得基因ROS的物理/遗传图谱， 分离物UR 2的独特序列。 我们还将尝试剖析这个基因 通过将选定的TS突变位点与表型 变换参数的表达式。 这些转换参数 还将研究野生型UR 1和UR 2。 深入探索研究 这些病毒对神经视网膜细胞的促有丝分裂活性也是 UR 1和UR 2的生物学表征目标。 我们计划 研究UR 1蛋白产物的细胞内定位， UR 2通过免疫荧光和分级分离研究转化的 非生产细胞 这些蛋白质与细胞骨架 将对组件进行调查。 我们将最终尝试识别 c-ros蛋白产物，与特定的 我们希望通过对UR 1基因序列的分析，阐明该基因在 正常细胞 希望这些研究能有助于理解 禽转化基因及其致癌机制的研究进展 转型

The present proposal deals with a series of investigations aimed at clarifying the mechanisms of oncogenic transformation by avian sarcoma viruses (ASV). The main effort will be to further characterize genetically and biologically two new ASV's, UR1 and UR2, recently described by us. We plan to isolate conditional (ts) and nonconditional partial deletion (ptd) mutants in order to obtain a physical/genetic map of the gene ros, the unique sequence of isolate UR2. We will also attempt to dissect this gene by correlating the sites of selected ts mutation with the phenotypic expression of transformation parameters. These transformation parameters will also be investigated for wild type UR1 and UR2. A detailed study of the mitogenic activity of these viruses for neuroretinal cells is also a goal of the biological characterization of UR1 and UR2. We plan to investigate the intracellular location of the protein products of UR1 and UR2 by immunofluorescent and fractionation studies of transformed nonproducing cells. The interaction of these proteins with cytoskeletal components will be investigated. We will finally attempt to identify the protein product of c-ros, the cellular gene homologous to the specific sequence of UR1 with the hope to elucidate the function of this gene in normal cells. These studies hopefully will contribute to the understanding of avian transforming genes and their mechanism(s) of oncogenic transformation.