GENETIC ANALYSIS OF THE SV40 LARGE TUMOR ANTIGEN

SV40 大肿瘤抗原的遗传分析

• 批准号: 3482489
• 负责人: JAMES M PIPAS
• 金额: $ 16.46万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482489
• 关键词: cell type; chemical structure function; epidermal growth factor; gene expression; gene mutation; genetic manipulation; genetic mapping; genetic transcription; immunoprecipitation; laboratory mouse; mutant; nucleic acid hybridization; nucleic acid sequence; oncogenic virus; oncoproteins; point mutation; protein sequence; simian virus 40; tissue /cell culture; transfection; transforming virus; tumor antigens; viral carcinogenesis; virus DNA; virus antigen; virus assembly; virus genetics; virus infection mechanism; virus protein; virus replication

The large tumor antigen (T antigen) of simian virus 40 (SV40) is a multifunctional protein that is required for several steps in productive viral infection. Thus, T antigen function(s) are required for viral DNA replication, the negative control of early- region mRNA synthesis, the activation of late-region transcription and at least one other, as yet unidentified step involving late gene expression or assembly. In addition to its role in production infection, T antigen acts as an oncogene in many cell-types, inducing the morphological transformation of cells in culture and tumors in animals. Studies from a number of laboratories have shown that the 708 amino acid protein consists of several functional domains, each of which can function somewhat independently of the rest of the polypeptide. In addition T antigen occurs in several oligomeric forms and subclasses that differ in their type and degree of posttranslational modification. One approach to learning to nature of each T antigen activity and its role in viral development and transformation is to isolate mutants that selectively affect individual functions. Towards this end we have been characterizing a collection of deletion and amino acid substitution mutants that alter T antigen structure. We propose to continue this approach with special emphasis on discerning those activities to T antigen that play a role in transformation. Thus, we plan to: (1) map the minimal sequences required for the transformation of different cell types and relate this activity to other T antigen functions; (2) assess the ability of this transforming region(s) to cooperate with other oncogenes and induce tumors in transgenic mice; (3) map the minimal sequences that induce transcriptional trans activation and assess the relation of this activity to transformation; and (4) continue to characterize selected mutants and recombinant viruses.

猿猴病毒40（SV40）的大肿瘤抗原（T抗原）是一种 多个步骤所需的多功能蛋白质 生产性病毒感染。 因此，T 抗原功能是 病毒DNA复制所需的早期阴性对照 区域 mRNA 合成，晚期区域激活 转录和至少一个其他尚未确定的步骤 涉及晚期基因表达或组装。 除了它的作用之外 在生产感染中，T抗原在许多细胞中充当癌基因 细胞类型，诱导细胞形态转变 动物培养和肿瘤。 来自许多研究 实验室证明，蛋白质由 708 个氨基酸组成 由多个功能域组成，每个功能域都可以发挥作用 某种程度上独立于多肽的其余部分。 在 另外 T 抗原以几种寡聚形式出现，并且 翻译后类型和程度不同的子类 修改。 了解每种 T 抗原活性性质的一种方法 它在病毒发育和转化中的作用是分离 选择性影响个体功能的突变体。 朝这个方向 最后我们已经描述了删除和的集合 改变T抗原结构的氨基酸取代突变体。 我们建议继续采用这种方法，特别强调 识别那些在 T 抗原中发挥作用的活性 转变。 因此，我们计划：（1）映射最小序列 不同细胞类型转化所需的并相互关联 这种活性对其他 T 抗原功能的影响； (2)评估能力 该转化区域与其他癌基因合作，并且 在转基因小鼠中诱发肿瘤； (3) 绘制最小序列 诱导转录反式激活并评估关系 这项活动的转变； (4) 继续 表征选定的突变体和重组病毒。