TRANSCRIPTIONAL ACTIVATION BY P53 CORRELATES WITH SUPPRESSION OF GROWTH BUT NOT TRANSFORMATION
TRANSCRIPTIONAL ACTIVATION BY P53 CORRELATES WITH SUPPRESSION OF GROWTH BUT NOT TRANSFORMATION
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DOI：
10.1016/0092-8674(94)90071-x
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发表时间：
1994-12-02
期刊：
影响因子：
64.5
通讯作者：
VOUSDEN, KH
中科院分区：
文献类型：
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作者：
CROOK, T;MARSTON, NJ;VOUSDEN, KH
肿瘤抑制蛋白p53显示了在癌症中检测到的突变蛋白经常丢失的生长和转化抑制功能。使用一个大系列的p53突变体，我们已经证明了一个很好的相关性之间的转录激活和生长抑制p53无效的人类细胞。然而，并非所有转录活性突变体都保留了抑制原代啮齿动物细胞转化的能力，两种肿瘤衍生的点突变体显示出转化和反式激活活性的一些证据。这些突变体的转化是不介导的内源性p53反式激活功能的反式显性抑制，表达这些p53蛋白的细胞系表现出升高的p53转录活性。我们的研究结果表明，激活转录调控p53不一定会导致肿瘤抑制。
The tumor suppressor protein p53 shows growth and transformation suppression functions that are frequently lost by mutant proteins detected in cancers. Using a large series of p53 mutants, we have demonstrated an excellent correlation between transcriptional activation and growth suppression in p53-null human cells. Not all transcriptionally active mutants retain the ability to suppress transformation in primary rodent cells, however, and two tumor-derived point mutants displayed some evidence of both transforming and transactivating activity. Transformation by these mutants was not mediated by transdominant repression of endogenous p53 transactivating function, and cell lines expressing these p53 proteins showed elevated p53 transcriptional activity. Our results suggest that activation of transcriptional regulation by p53 will not necessarily result in tumor suppression.