THE TRANSFORMING GENES OF AVIAN SARCOMA VIRUSES

本提案涉及一系列调查，目的是 禽肉瘤致癌转化机制的研究进展 病毒(ASV)。主要的努力将是进一步确定基因的特征 在生物学上，我们最近描述了两种新的ASV，UR1和UR2。我们 计划隔离条件(Ts)和非条件部分删除(Ptd) 为了获得ros基因的物理/遗传图谱， 分离株UR2的唯一序列。我们还将尝试剖析这种基因 通过将所选ts突变的位置与表型相关联 变换参数的表达式。这些变换参数 还将对野生型UR1和UR2进行调查。对……的详细研究 这些病毒对神经视网膜细胞的有丝分裂活性也是 UR1和UR2生物学特性的目标。我们计划 研究UR1和UR1蛋白产物的细胞内定位 用免疫荧光和分级法研究UR2的转化 不生产的细胞。这些蛋白质与细胞骨架的相互作用 将对组件进行调查。我们将最终尝试确定 C-ros的蛋白产物，与特定基因同源的细胞基因 UR1基因的序列，以期阐明该基因的功能 正常细胞。这些研究有望有助于理解 禽类转化基因及其致癌机制的研究(S) 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.