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首页> 外文期刊>Molecular and Cellular Biology >General Transcriptional Coactivator PC4 Activates p53 Function
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General Transcriptional Coactivator PC4 Activates p53 Function

机译：通用转录共激活因子PC4激活p53功能

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The function of p53 is modulated by several transcriptional coactivators that regulate its tumor suppressor activity. Here we report that human transcriptional coactivator PC4 enhances the DNA binding of p53 to its cognate site in vitro and directly interacts with p53 in vivo. In vitro interaction studies demonstrated that the C-terminal 30 amino acids (364 to 393) of p53 strongly interact with PC4. Surprisingly, PC4 also stimulates the sequence-specific DNA binding of p53 with the C-terminal 30 amino acids deleted (p53Δ30), suggesting that PC4 mediates enhancement of p53 DNA binding by a unique mechanism. We also demonstrated that PC4 can stimulate p53- and p53Δ30-mediated transactivation from a p53-responsive promoter. Furthermore, PC4 enhances p53- and p53Δ30-dependent apoptosis by inducing bax (a p53-targeted proapoptotic gene) gene expression. These results establish the first physiological role of PC4 as a transcriptional coactivator.
机译：p53的功能受到几种调节其抑癌活性的转录共激活因子的调控。在这里，我们报道人类转录共激活因子PC4在体外增强了p53与其同源位点的DNA结合，并在体内直接与p53相互作用。体外相互作用研究表明，p53的C端30个氨基酸（364至393）与PC4强烈相互作用。令人惊讶地，PC4还刺激p53的C-末端30个氨基酸缺失的序列特异性DNA结合（p53Δ30），表明PC4通过独特的机制介导了p53 DNA结合的增强。我们还证明了PC4可以刺激p53反应性启动子对p53和p53Δ30介导的反式激活。此外，PC4通过诱导 bax （p53靶向的促凋亡基因）基因表达增强p53和p53Δ30依赖性细胞凋亡。这些结果确立了PC4作为转录共激活因子的第一个生理作用。

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