Transformation by simian virus 40 does not involve the mutational activation of p53 to an oncogenic form.

Transformation by simian virus 40 does not involve the mutational activation of p53 to an oncogenic form.
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猿猴病毒 40 的转化不涉及 p53 突变激活至致癌形式。

DOI:
10.1016/0042-6822(90)90258-s
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发表时间:
1990
期刊:
影响因子:
3.7
通讯作者:
Simmons,DT
Simmons,DT
中科院分区:
医学3区
文献类型:
--
作者:
Lin,JY;Simmons,DT

文献摘要

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我们研究了SV40转化的小鼠细胞的P53蛋白是否与构象依赖的单抗pAb246发生反应。这种抗体通常可以区分具有抗增殖活性的p53(如野生型蛋白)(pAb246+)和具有致癌活性的突变型p53(pAb246−)。在筛选的13个细胞系中,12个细胞系含有pAb246+形式的P53,1个细胞系含有pAb246−形式。我们发现SV40不会引起后一种细胞系P53的激活突变,因为其来源的细胞也是pAb246−。级联免疫沉淀实验表明,在被检测的三个SV40转化的细胞系中,所有的p53都是pAb246+形式的,因此少量的pAb246−p53不太可能与这些细胞的转化特性有关。因此,我们得出结论,SV40介导的小鼠细胞转化不依赖于其P53向致癌形式的激活,并且在所有可能性中,允许发生转化的部分原因是SV40T抗原阻断了P53的抗增殖活性。
We investigated whether the p53 protein of SV40-transformed mouse cells reacted with the conformation-dependent monoclonal antibody pAb246. This antibody can usually distinguish between a p53 with anti-proliferative activity like the wild-type protein (pAb246+) and a mutated form of p53 with oncogenic activity (pAb246−). Of the 13 cell lines that were screened, 12 contained the pAb246+form of p53 and one had the pAb246−form. We showed that SV40 did not induce an activating mutation in the p53 of this latter cell line, because the cells from which it was derived were also pAb246−. Cascade immunoprecipitation experiments demonstrated that in three SV40-transformed cell lines that were examined, all of the p53 was of the pAb246+form making it unlikely that small amounts of pAb246−p53 were responsible for the transformation properties of these cells. We therefore concluded that SV40-mediated transformation of murine cells is not dependent on the activation of their p53 to an oncogenic form, and that, in all probability, transformation is allowed to occur in part because the anti-proliferative activity of p53 is blocked by SV40 T antigen.