PROTEIN SYNTHESIS DURING ONCOGENIC TRANSFORMATION

致癌转化过程中的蛋白质合成

• 批准号: 4691889
• 负责人: H L COOPER
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4691889
• 关键词: Retroviridae; gel electrophoresis; gene expression; neoplastic cell; oncogenes; oncoproteins; viral carcinogenesis

We compared 2-dimensional electropherograms of newly synthesized proteins from lines of NIH/3T3 cells transformed by a variety of retroviral oncogenes, from cellular revertant lines, and from a line (433.3) which expresses the v-ras oncogene in response to corticosteroids. We detected 7 proteins whose synthesis was strongly suppressed in cell lines tranformed by each of the six retroviral oncogenes we studied, and whose production was fully orpartially restored in two cellular revertant lines. Suppression of two of these proteins was also correlated with the initial appearance of morphological alteration during steroid-induced oncogene expression in 433.3 cells. These proteins (p37/4.78 and p41/4.75) were identified as tropomyosins, a group of at least 5 cytoskeletal proteins. Transformation by the papova viruses, SV-40 and polyoma, caused no suppression of synthesis of these tropomyosins. This indicated that suppression of tropomyosin synthesis is not a nonspecific response by cells to being forced to grow with the transformed phenotype, but is specifically associated with oncogenesis by diverse retroviral oncogenes. The results are consistent with the hypothesis that the different biochemical processes initiated by expression of structurally diverse retroviral oncogenes may converge on a limited number of common targets, one of which is the mechanism which regulates the synthesis of tropomyosins.

我们比较了新合成的蛋白质的二维电泳图， 从NIH/3 T3细胞系转化的各种逆转录病毒 癌基因，来自细胞回复突变系，以及来自 表达V-ras癌基因以响应皮质类固醇。 我们检测到7个 在转化的细胞系中合成受到强烈抑制的蛋白质 我们研究的六种逆转录病毒癌基因的每一种， 在两个细胞回复系中完全或部分恢复。 其中两种蛋白质的抑制也与最初的 激素诱导癌基因表达过程中出现形态学改变 在433.3细胞中表达。 这些蛋白（p37/4.78和p41/4.75）是 被鉴定为原肌球蛋白，一组至少5种细胞骨架蛋白。 通过乳多空病毒SV-40和多瘤病毒的转化， 抑制这些原肌球蛋白的合成。 这表明 抑制原肌球蛋白合成不是细胞的非特异性反应 被迫与转化的表型一起生长，但特别是 与多种逆转录病毒癌基因的肿瘤发生有关。 结果 与不同的生化过程 由结构上不同的逆转录病毒癌基因的表达启动的， 集中在有限数量的共同目标上，其中之一是 调节原肌球蛋白合成的机制。