THE TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

禽RNA肿瘤病毒的转化基因

• 批准号: 3170280
• 负责人: PIERO C BALDUZZI
• 金额: $ 9.78万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1990-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3170280
• 关键词: Retroviridae disease; alpharetrovirus; fluorescent dye /probe; gene expression; genetic mapping; immunofluorescence technique; mutant; nonmammalian vertebrate embryology; nucleic acid sequence; retina; temperature sensitive mutant; transforming virus; viral leukemogenesis; virus genetics

The purpose of the proposed research is to elucidate the function(s) of the oncogene v-ros present in avian sarcoma virus UR2 described by us. We have recently discovered that the oncogene products p68ros of avian sarcoma virus UR2 is associated with a phosphatidyl inositol (PtdIns) kinase activity in vitro, and the UR2 transformed cells show enhanced polyphosphoinositide turnover. It is possible that ptdIns phosphorylation might contribute to malignant transformation of susceptible cells by generating abnormally high levels of 1,2-diacylglycerol, which appears to be the endogeneous activator of the phorbol ester receptor (kinase C). similar observations have been made on ppSrc by Sugimoto et al. We intend to investigate whether the kinase activity associated with p68ros is an intrinsic property of the protein or whether this protein has a regulatory role in the phosphorylation of phosphoinositols. We plan to answer this question by introducing the molecularly cloned genome of UR2 in expression vectors and obtain expression of p68ros in prokaryotic cells. We also propose to continue our genetic studies of UR2 AV and carry out a genetic analysis of the ros gene in an attempt to correlate specific lesions, small deletions, and point mutations in the ros sequence, with specific phenotypes of the transformed cells. The goal of this investigation is to obtain a physical-genetic map of this oncogene. We finally plan to investigate the interaction of avian vital oncogene expression and development of differentiation markers in neuroretinal cells in an attempt to shed light on the normal function of the corresponding proto-oncogenes.

拟议研究的目的是阐明 癌基因v-ros存在于我们描述的禽肉瘤病毒UR 2中。 我们最近发现，禽类的癌基因产物p68 ros 肉瘤病毒UR 2与磷脂酰肌醇（PtdIns）相关 激酶活性，并且UR 2转化的细胞显示增强的 多聚磷酸肌醇周转 ptdIns的磷酸化可能 可能导致易感细胞的恶性转化， 产生异常高水平的1，2-甘油二酯， 是佛波酯受体（激酶C）的内源性激活剂。 Sugimoto等人也对ppSrc进行了类似的观察，我们打算 为了研究与p68 ros相关的激酶活性是否是 蛋白质的内在特性或该蛋白质是否具有调节性 在磷酸肌醇磷酸化中的作用。 我们计划回答这个问题 通过在表达中引入UR 2的分子克隆基因组来解决问题 载体并获得p68 ros在原核细胞中的表达。 我们也 我建议继续我们对UR 2 AV的遗传研究，并进行遗传学研究。 ROS基因的分析，试图将特定的病变，小的 ROS序列中的缺失和点突变， 转化细胞的表型。 这次调查的目的是 获得该致癌基因的物理遗传图谱。 最后，我们计划研究禽类重要癌基因之间的相互作用， 神经视网膜细胞分化标志物的表达和发育 试图阐明相应的正常功能， 原癌基因