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Modulation of p53 protein expression during cellular transformation with simian virus 40.

机译:猿猴病毒40细胞转化过程中p53蛋白表达的调节。

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We analyzed the relation of metabolic stabilization of the p53 protein during cellular transformation by simian virus 40 (SV40) to (i) expression of the transformed phenotype and (ii) expression of the large tumor antigen (large T). Analysis of SV40-tsA28-mutant-transformed rat cells (tsA28.3 cells) showed that both p53 complexed to large T and free p53 (W. Deppert and M. Haug, Mol. Cell. Biol. 6:2233-2240, 1986) were metabolically stable when the cells were cultured at 32 degrees C and expressed large T and the transformed phenotype. At the nonpermissive temperature (39 degrees C), large-T expression is shut off in these cells and they revert to the normal phenotype. In such cells, p53 was metabolically unstable, like p53 in untransformed cells. To determine whether metabolic stabilization of p53 is directly controlled by large T, we next analyzed the metabolic stability of complexed and free p53 in SV40 abortively infected normal BALB/c mouse 3T3 cells. We found that neither p53 in complex with large T nor free p53 was metabolically stable. However, both forms of p53 were stabilized in SV40-transformed cells which had been developed in parallel from SV40 abortively infected cultures. Our results indicate that neither formation of a complex of p53 with large T nor large-T expression as such is sufficient for a significant metabolic stabilization of p53. Therefore, we suggest that metabolic stabilization of p53 during cellular transformation with SV40 is mediated by a cellular process and probably is the consequence of the large-T-induced transformed phenotype.
机译:我们分析了猿猴病毒40(SV40)在细胞转化过程中p53蛋白的代谢稳定与(i)转化表型的表达和(ii)大肿瘤抗原(大T)的表达之间的关系。 SV40-tsA28突变转化的大鼠细胞(tsA28.3细胞)的分析表明,p53都与大T和游离p53结合(W. Deppert和M. Haug,分子细胞生物学,6:2233-2240,1986)当在32℃下培养细胞并表达大T和转化表型时,其代谢稳定。在不允许的温度(39摄氏度)下,这些细胞中的大T表达被关闭,它们恢复为正常表型。在此类细胞中,p53在代谢上不稳定,就像未转化细胞中的p53一样。为了确定p53的代谢稳定是否直接受大T控制,我们接下来分析了SV40流产感染的正常BALB / c小鼠3T3细胞中复合和游离p53的代谢稳定性。我们发现与大T复合体中的p53或游离p53都不是代谢稳定的。但是,两种形式的p53在SV40转化的细胞中都稳定了,这些细胞是从SV40感染性感染的培养物中平行培养出来的。我们的结果表明,既不形成具有大T的p53的复合物,也不形成具有大T的表达,不足以显着稳定p53的代谢。因此,我们建议SV40细胞转化过程中p53的代谢稳定是由细胞过程介导的,可能是大T诱导的转化表型的结果。

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