Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence.
Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence.
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发表时间：
2003
期刊：
影响因子：
64.8
通讯作者：
A. Takaoka;S. Hayakawa;H. Yanai;D. Stoiber;Hideo Negishi;H. Kikuchi;S. Sasaki;K. Imai;T. Shibue;K. Honda;T. Taniguchi
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作者：
A. Takaoka;S. Hayakawa;H. Yanai;D. Stoiber;Hideo Negishi;H. Kikuchi;S. Sasaki;K. Imai;T. Shibue;K. Honda;T. Taniguchi
快速消除不需要的细胞是肿瘤抑制和免疫的重要特征。肿瘤抑制因子p53和干扰素-α和-β（IFN-α/β）分别对于癌细胞和抗病毒免疫应答中的细胞凋亡的诱导是必不可少的，但关于它们的相互关系知之甚少。在这里，我们表明，p53基因的转录诱导IFN-α/β，伴随着p53蛋白水平的增加。IFN-α/β信号本身并不激活p53;相反，它有助于增强p53对应激信号的反应。我们展示了IFN-α/β诱导p53基因有助于肿瘤抑制的例子。此外，我们还表明，p53在病毒感染的细胞中被激活以引发细胞凋亡反应，并且p53对于宿主的抗病毒防御至关重要。我们的研究揭示了迄今未被认识的p53和IFN-α/β之间的联系，在肿瘤抑制和抗病毒免疫，这可能有治疗意义。
Swift elimination of undesirable cells is an important feature in tumour suppression and immunity. The tumour suppressor p53 and interferon-alpha and -beta (IFN-alpha/beta) are essential for the induction of apoptosis in cancerous cells and in antiviral immune responses, respectively, but little is known about their interrelationship. Here we show that transcription of the p53 gene is induced by IFN-alpha/beta, accompanied by an increase in p53 protein level. IFN-alpha/beta signalling itself does not activate p53; rather, it contributes to boosting p53 responses to stress signals. We show examples in which p53 gene induction by IFN-alpha/beta contributes to tumour suppression. Furthermore, we show that p53 is activated in virally infected cells to evoke an apoptotic response and that p53 is critical for antiviral defence of the host. Our study reveals a hitherto unrecognized link between p53 and IFN-alpha/beta in tumour suppression and antiviral immunity, which may have therapeutic implications.