TRANSFORMING GENES OF AVIAN SARCOMA VIRUSES

这项建议的目的有两个，其一是理解 禽肉瘤病毒转化基因v-onc的性质和功能 和其正常的细胞同源基因c-onc；另一种是阐明 逆转录病毒与细胞序列重组的机制 肉瘤病毒的形成过程。 一种新鉴定的禽肉瘤病毒UR2将被用作模型。 系统研究v-onc和c-onc的结构、序列和功能。 UR2的转化基因v-ros及其细胞同源基因c-ros， 将通过分子克隆和测序进行分析。按顺序排列 V-ros将与其他编码蛋白激酶的v-onc基因进行比较，以 阐明它们的结构和功能关系。该序列和 将比较c-ros和v-ros的转换能力，看看是否有 存在一个根本的差异，这可能会区分致癌的 这两个基因的潜力。C-ros的结构和表达水平 将在发育鸡的不同组织中进行研究，以阐明 C-ros在正常细胞中的作用。细胞内的定位和相互作用 含有细胞蛋白质的v-ros产物，例如细胞骨架，将是 分析以追求转型的过程，特别是 了解UR2在雏鸡身上独特转化形态的基础 细胞。C-SRS基因的mR-NA将被分子克隆，以研究其 结构和潜在的转化能力。 禽恢复肉瘤病毒(RASV)系统已被 来自Rous肉瘤病毒src缺失突变体的将用于 病毒与细胞间重组机制的研究 序列。对RASV的产生至关重要的病毒序列将 被定义。重组位点和c-src序列参与的 进程将被定位。

The objectives of this proposal are two fold, one is to understand the nature and function of the transforming gene of avian sarcoma virus, v-onc, and its normal cellular counterpart, c-onc; the other is to elucidate the mechanism of the recombination between retroviral and cellular sequences in the process of the formation of sarcoma viruses. A newly characterized avian sarcoma virus, UR2, will be used as a model system to study the structure, sequence and function of v-onc and c-onc. The transforming gene of UR2, v-ros, and its cellular homologue, c-ros, will be analyzed by molecular cloning and sequencing. The sequence of v-ros will be compared with other v-onc genes coding for protein kinases to elucidate their structural and functional relationship. The sequence and transforming ability of c-ros and v-ros will be compared to see if there exists a fundamental difference that may differentiate the oncogenic potential of the two genes. The structure and level of expression of c-ros in various tissues of developing chickens will be studied to elucidate the role of c-ros in normal cells. The intracellular location and interaction of the v-ros product with cellular proteins, e.g. cytoskeletons, will be analyzed to pursue the process of transformation, in particular, to understand the basic for the unique transforming morphology of UR2 on chick cells. The mRNA of c-srs gene will be molecularly cloned to study its structure and potential transforming ability. The system of avian recovered sarcoma viruses (rASVs) that have been derived from src deletion mutants of Rous sarcoma virus will be used in the study of the mechanism of recombination between viral and cellular sequences. The viral sequence essential for the generation of rASVs will be defined. The sites of recombination and c-src sequences involved in the process will be located.