GENETIC ANALYSIS OF THE SV40 LARGE TUMOR ANTIGEN

SV40 大肿瘤抗原的遗传分析

• 批准号: 3482485
• 负责人: JAMES M PIPAS
• 金额: $ 18.94万
• 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 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482485
• 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.

猴病毒40(SV40)大肿瘤抗原(T抗原)是一种 一种多功能蛋白质，它是体内几个步骤所必需的 有效的病毒感染。因此，T抗原功能(S)是 病毒DNA复制所需的，早期负控制- 区域信使核糖核酸合成，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的。除了它的作用之外 在产生性感染中，T抗原在许多情况下充当癌基因 细胞类型，诱导细胞形态转化 动物的培养和肿瘤。来自多项研究的 实验室已经证明，708个氨基酸的蛋白质由 由几个功能域组成，每个功能域都可以 在某种程度上独立于多肽的其余部分。在……里面 附加T抗原以几种寡聚形式存在，并且 在翻译后的类型和程度上不同的子类 修改。 一种学习每个T抗原活性和性质的方法 它在病毒发展和转化中的作用是分离出 选择性地影响个体功能的突变体。朝向这个方向 我们一直在描述一组删除和 改变T抗原结构的氨基酸替代突变体。 我们建议继续这一做法，特别强调 识别对T抗原起作用的那些活动 转型。因此，我们计划：(1)映射最小序列 不同细胞类型和关联的转换所需 这种活性对其他T抗原功能的影响；(2)评估 这个转化区域(S)与其他癌基因和 转基因小鼠诱发肿瘤；(3)定位最小序列 诱导转录反式激活并评估其与 这项活动的转型；以及(4)继续 确定选定的突变体和重组病毒的特征。