MOLECULAR MECHANISMS OF POLYOMA-INDUCED TRANSFORMATION

多瘤诱导转化的分子机制

• 批准号: 3482171
• 负责人: THOMAS M ROBERTS
• 金额: $ 26.15万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482171
• 关键词: Polyomavirus muris 1; alcohol phosphotransferase; binding proteins; cell transformation; enzyme activity; enzyme mechanism; gene mutation; genetic library; growth factor receptors; immunoaffinity chromatography; immunoprecipitation; laboratory mouse; molecular cloning; mutant; nucleic acid sequence; oncogenes; oncogenic virus; phosphoproteins; phosphorylation; protein sequence; protein structure function; protein tyrosine kinase; protooncogene; site directed mutagenesis; tissue /cell culture; tumor antigens; virus antigen; virus genetics

Studies will be carried out on the mechanisms by which polyoma virus's middle T antigen transforms cultured fibroblasts. Since middle T has no known biochemical activity it is thought to transform by binding to and modulating the activities of certain key cellular proteins. Hence these studies will focus on two complementary aspects of middle T antigen: First a series of genetic studies will be carried out on middle T. These will be aimed at determining how many key sites on the molecule are important to transformation. As sites are defined they will be tested to see into which complementation group they fall. Additional genetic studies will be carried out on two known motifs as well. Biochemical studies will focus on Mtag's interaction with the Pi3' kinase and the 27/29kDa cellular proteins which are bound by Mtag and on identifying cellular proteins which are phosphorylated on tyrosine in Mtag transformed cells.

将研究多瘤病毒的机制 中间T抗原转化培养的成纤维细胞。 由于中间T没有 已知的生化活性，它被认为通过结合和转化 调节某些关键细胞蛋白质的活性。 因此这些 研究将集中于中 T 抗原的两个互补方面： 首先将对中 T 进行一系列遗传学研究。这些 旨在确定分子上有多少个关键位点 对转型很重要。 当站点被定义时，它们将被测试 看看他们属于哪个互补组。 额外遗传 研究还将针对两个已知的主题进行。 生化 研究将集中于 Mtag 与 Pi3' 激酶的相互作用以及 与 Mtag 结合并识别的 27/29kDa 细胞蛋白 Mtag 中酪氨酸磷酸化的细胞蛋白 转化的细胞。