Cooper H L, Feuerstein N, Noda M, Bassin R H
Mol Cell Biol. 1985 May;5(5):972-83. doi: 10.1128/mcb.5.5.972-983.1985.
To identify proteins whose production may be altered as a common event in the expression of structurally diverse oncogenes, we compared two-dimensional electropherograms of newly synthesized proteins from NIH/3T3 cell lines 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. Most alterations in the synthesis of specific proteins detected by this approach appeared to be the result of selection during prolonged cultivation and were probably unrelated to the transformation process. However, we detected seven proteins whose synthesis was strongly suppressed in cell lines transformed by each of the six retroviral oncogenes we studied and whose production was fully or partially restored in two cellular revertant lines. Suppression of two of these proteins was also correlated with the initial appearance of morphological alteration during corticosteroid-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 five cytoskeletal proteins. Transformation by the papovaviruses simian virus 40 and polyomavirus caused no suppression of synthesis of these tropomyosins. This indicates 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.
为了鉴定那些在结构多样的癌基因表达过程中其产生可能作为常见事件而发生改变的蛋白质,我们比较了来自经多种逆转录病毒癌基因转化的NIH/3T3细胞系、细胞回复系以及来自一个(433.3)在皮质类固醇作用下表达v-ras癌基因的细胞系中新合成蛋白质的二维电泳图谱。通过这种方法检测到的特定蛋白质合成中的大多数改变似乎是长期培养过程中选择的结果,可能与转化过程无关。然而,我们检测到七种蛋白质,它们在我们研究的六种逆转录病毒癌基因转化的细胞系中合成受到强烈抑制,而在两个细胞回复系中其产生完全或部分恢复。在433.3细胞中皮质类固醇诱导癌基因表达期间,这两种蛋白质(p37/4.78和p41/4.75)的抑制也与形态改变的最初出现相关。这些蛋白质被鉴定为原肌球蛋白,是一组至少五种细胞骨架蛋白质。猿猴病毒40和多瘤病毒这两种乳头瘤病毒的转化并未导致这些原肌球蛋白合成的抑制。这表明原肌球蛋白合成的抑制不是细胞对被迫以转化表型生长的非特异性反应,而是与多种逆转录病毒癌基因的致癌作用特异性相关。这些结果与以下假设一致,即由结构多样的逆转录病毒癌基因表达引发的不同生化过程可能汇聚于有限数量的共同靶点,其中之一是调节原肌球蛋白合成的机制。