DIFFERENT TUMOR-DERIVED P53 MUTANTS EXHIBIT DISTINCT BIOLOGICAL-ACTIVITIES
DIFFERENT TUMOR-DERIVED P53 MUTANTS EXHIBIT DISTINCT BIOLOGICAL-ACTIVITIES
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DOI：
10.1126/science.2218501
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发表时间：
1990-10-05
期刊：
影响因子：
56.9
通讯作者：
OREN, M
中科院分区：
文献类型：
--
作者：
HALEVY, O;MICHALOVITZ, D;OREN, M
在其野生型中，p53蛋白可以干扰肿瘤过程。肿瘤来源的细胞通常表达突变的p53。迄今为止，从转化的小鼠细胞中分离出的p53的全长度突变形式在体外表现出三个共同的特性：失去转化抑制活性，获得明显的转化潜力，并且能够结合热休克蛋白同源hsc70。一种肿瘤衍生的小鼠p53变体现在被描述，其突变位点对应于p53在人类肿瘤中的热点。虽然绝对没有抑制作用，但它只是微弱的转化，没有检测到hsc70的结合。这些数据表明，p53突变体结合内源性p53的能力并不是其致癌潜力的唯一决定因素。这些数据也支持功能获得型p53突变体的存在。
In its wild-type form, the protein p53 can interfere with neoplastic processes. Tumor-derived cells often express mutant p53. Full-length mutant forms of p53 isolated so far from transformed mouse cells exhibit three common properties in vitro: loss of transformation-suppressing activity, gain of pronounced transforming potential, and ability to bind the heat shock protein cognate hsc70. A tumor-derived mouse p53 variant is now described, whose site of mutant corresponds to a hot spot for p53 in human tumors. While absolutely nonsuppressing, it is only weakly transforming and exhibits no detectable hsc70 binding. The data suggest that the ability of a p53 mutant to bind endogenous p53 is not the sole determinant of its oncogenic potential. The data also support the existence of gain-of-function p53 mutants.