ADENOVIRUS 1P LOCUS: ROLE IN OCOGENIC TRANSFORMATION

我们已经分离出一些转化缺陷的大斑块（LP） 腺病毒2的突变体。 一些lp突变体在一个狭窄的 病毒基因组的mp4.5至5.8之间的片段， Elb-19 K多肽合成。 Ad 2 lp突变体类似于Ad 12 cyt 也是转化缺陷型的突变体（Takemori等，1968年）。 我们建议深入研究lp+和cyt+基因座在 细胞转化和肿瘤发生。 我们将进行详细的 通过物理作图表征Ad 2 lp和Ad 12 cyt突变体， 互补分析。 lp突变对细胞参数的影响 如细胞骨架结构的丧失， 纤溶酶原激活剂，和锚定的独立性通常与 将研究转化的细胞。 lp基因座的作用， 将使用TS研究转化的启动或维持 lp td突变体。 我们将绘制Elb-19 K的功能结构域， 细胞转化和肿瘤发生。 为了解 Elb-19 K诱导细胞转化的机制，我们将确定 与19 K相关的细胞靶蛋白和19 K介导的 细胞成分的变化。

We have isolated a number of transformation defective large plaque (lp) mutants of adenovirus 2. Some of the lp mutants map within a narrow segment of the viral genome between mp 4.5 to 5.8 and are defective in synthesis of Elb-19K polypeptide. The Ad2 lp mutants resemble the Ad12 cyt mutants which are also transformation defective (Takemori et al., 1968). We propose an indepth investigation of the role of lp+ and cyt+ loci in cellular transformation and in tumorigenesis. We will carry out detailed characterization of the Ad2 lp and Ad12 cyt mutants by physical mapping and complementation analysis. Effect of lp mutation on the cellular parameters such as the loss of cytoskeletal structures, increased secretion of plasminogen activator, and anchorage independence normally associated with transformed cells will be investigated. The role of the lp locus in the initiation or maintenance of transformation will be investigated using ts lp td mutants. We will map the functional domains of Elb-19K essential for cellular transformation and for tumorigenesis. In order to understand the mechanism of Elb-19K induced cellular transformation, we will identify the cellular target proteins associated with 19K and the 19K-mediated modifications of the cellular components.