THE TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

禽RNA肿瘤病毒的转化基因

• 批准号: 3170277
• 负责人: PIERO C BALDUZZI
• 金额: $ 9.71万
• 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/3170277
• 关键词: 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(S)的功能 我们所描述的禽肉瘤病毒UR2中存在癌基因v-ros。 我们最近发现禽类的癌基因产物p68ros 肉瘤病毒UR2与磷脂酰肌醇(PtdIns)相关 体外活性测定表明，UR2转化的细胞表现出较强的活性 多磷肌醇周转率。有可能ptdIns的磷酸化 可能通过以下途径促进易感细胞的恶性转化 产生异常高水平的1，2-二酰基甘油，这似乎会 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p68ros相关的激酶活性是否是一种 该蛋白质的固有属性或该蛋白质是否具有调节 在磷酸肌醇的磷酸化中的作用。我们计划回答这个问题 通过介绍UR2分子克隆基因组在表达中提出的问题 并获得p68ros在原核细胞中的表达。我们也 建议继续我们对UR2病毒的遗传学研究，并进行遗传学研究 对ros基因的分析试图将特定的小病变联系起来。 Ros序列中的缺失和点突变，具有特定的 转化细胞的表型。这次调查的目的是 获得这种致癌基因的物理遗传图谱。 我们最终计划研究禽类致癌基因之间的相互作用 分化标记物在神经视网膜细胞中的表达和发展 试图阐明相应的 原癌基因。