Inactivation of the cellular p53 gene is a common feature of Friend virus-induced erythroleukemia: relationship of inactivation to dominant transforming alleles-猫眼课题宝

细胞 p53 基因失活是弗兰德病毒诱导的红白血病的一个共同特征：失活与显性转化等位基因的关系

DOI：

发表时间：

1990

期刊：

Molecular and Cellular Biology

影响因子：

5.3

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

D. Munroe;J. Peacock;S. Benchimol

Friend红白血病病毒复合体不含细胞源性癌基因。因此，这种病毒的转化可能涉及影响细胞基因表达的突变。我们提供的证据表明，细胞p53基因失活突变是Friend病毒诱导的恶性肿瘤的共同特征，这与p53在该疾病中的反基因作用一致。我们已经证明，p53基因的频繁重排会导致缺失表达或截断蛋白的合成，而在其他Friend细胞系中可以看到p53蛋白的过表达。我们现在证明，p53在后者细胞中的表达也是异常的，这是编码高度保守氨基酸区域的错义突变的结果。从不同小鼠的细胞中获得的这些异常等位基因中的三个被克隆出来，并在基因转移试验中发现它们作为显性致癌基因发挥作用，这支持了p53中某些自然发生的错义突变赋予编码蛋白显性阴性表型的观点。

The Friend erythroleukemia virus complex contains no cell-derived oncogene. Transformation by this virus may therefore involve mutations affecting cellular gene expression. We provide evidence that inactivating mutations of the cellular p53 gene are a common feature in Friend virus-induced malignancy, consistent with an antioncogene role for p53 in this disease. We have shown that frequent rearrangements of the p53 gene cause loss of expression or synthesis of truncated proteins, whereas overexpression of p53 protein is seen in other Friend cell lines. We now demonstrate that p53 expression in the latter cells is also abnormal, as a result of missense mutations in regions encoding highly conserved amino acids. Three of these aberrant alleles obtained from cells from different mice were cloned and found to function as dominant oncogenes in gene transfer assays, supporting the view that certain naturally occurring missense mutations in p53 confer a dominant negative phenotype on the encoded protein.