WILD-TYPE P53 ACTIVATES TRANSCRIPTION INVITRO
WILD-TYPE P53 ACTIVATES TRANSCRIPTION INVITRO
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DOI：
10.1038/358083a0
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发表时间：
1992-07-02
期刊：
影响因子：
64.8
通讯作者：
PRIVES, C
中科院分区：
文献类型：
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作者：
FARMER, G;BARGONETTI, J;PRIVES, C
p53 蛋白是人类癌症的重要决定因素，可调节培养物 1-3 中细胞的生长。已知它是一种序列特异性 DNA 结合蛋白 4,5，具有强大的激活结构域 6-8，但尚未确定它是否直接调节转录。在这里，我们展示了完整的纯化野生型人和鼠 p53 蛋白在体外强烈激活转录。这种激活取决于 p53 与带有 p53 结合序列的模板结合的能力。相比之下，肿瘤来源的突变型 p53 蛋白根本无法激活模板的转录，当与野生型 p53 复合时，这些突变体会阻止野生型蛋白的转录激活。此外，猿猴病毒40大T抗原抑制野生型p53激活转录。我们的结果支持 p53 直接激活转录的模型，但这种活性可以通过与野生型 p53 相互作用而被突变体 p53 和 SV40 大 T 抗原抑制。
THE p53 protein is an important determinant in human cancer and regulates the growth of cells in culture 1-3. It is known to be a sequence-specific DNA-binding protein 4,5 with a powerful activation domain 6-8, but it has not been established whether it regulates transcription directly. Here we show that intact purified wild-type human and murine p53 proteins strongly activate transcription in vitro. This activation depends on the ability of p53 to bind to a template bearing a p53-binding sequence. By contrast, tumour-derived mutant p53 proteins cannot activate transcription from the template at all, and when complexed to wild-type p53, these mutants block transcriptional activation by the wild-type protein. Moreover, the simian virus 40 large T antigen inhibits wild-type p53 from activating transcription. Our results support a model in which p53 directly activates transcription but this activity can be inhibited by mutant p53 and SV40 large T antigen through interaction with wild-type p53.