THE TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

禽RNA肿瘤病毒的转化基因

基本信息

批准号：
3170282
负责人：
PIERO C BALDUZZI
金额：
$ 10.46万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-03-01 至 1990-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3170282
关键词：
Aves 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 virus protein

项目摘要

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美国描述的禽类肉瘤病毒UR2中存在的癌基因V-ROS。我们最近发现，雅芳的癌基因产品p68ros 肉瘤病毒UR2与磷脂酰肌醇（PTDINS）有关在体外激酶活性，UR2转化的细胞显示出增强的多磷酸固醇周转率。 PTDINS磷酸化可能可能导致易感细胞的恶性转化产生异常高的1,2-二酰基甘油，似乎成为佛波酯受体（激酶C）的内差激活剂。 Sugimoto等人对PPSRC进行了类似的观察。我们打算研究与p68ros相关的激酶活性是否是一种蛋白质的内在特性或该蛋白是否具有调节性在磷酸肌醇的磷酸化中的作用。我们计划回答这个通过在表达中引入UR2的分子克隆基因组来提出问题向量并获得核细胞中p68ros的表达。我们也是建议继续我们对UR2 AV的遗传研究并进行遗传对ROS基因的分析，试图将特定病变相关联，小 ROS序列中的删除和点突变，具有特定转化细胞的表型。这项调查的目的是获得该癌基因的物理遗传图。我们终于计划研究鸟类生命致癌基因的相互作用神经视网膜细胞中分化标记的表达和发展试图阐明相应的正常功能原始基因。