Lin J Y, Simmons D T
School of Life and Health Sciences, University of Delaware, Newark 19716.
Virology. 1990 May;176(1):302-5. doi: 10.1016/0042-6822(90)90258-s.
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.
我们研究了SV40转化的小鼠细胞中的p53蛋白是否与构象依赖性单克隆抗体pAb246发生反应。该抗体通常能够区分具有抗增殖活性的p53(如野生型蛋白,pAb246阳性)和具有致癌活性的p53突变形式(pAb246阴性)。在筛选的13个细胞系中,12个含有pAb246阳性形式的p53,1个含有pAb246阴性形式。我们发现SV40并未在后者细胞系的p53中诱导激活突变,因为其来源的细胞也是pAb246阴性。级联免疫沉淀实验表明,在检测的三个SV40转化细胞系中,所有p53均为pAb246阳性形式,这使得少量pAb246阴性p53导致这些细胞的转化特性的可能性不大。因此,我们得出结论,SV40介导的小鼠细胞转化不依赖于其p53激活为致癌形式,而且很可能转化的发生部分是因为p53的抗增殖活性被SV40 T抗原阻断。