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Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence

机译:干扰素-α/β信号转导与p53反应在肿瘤抑制和抗病毒防御中的整合

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Swift elimination of undesirable cells is an important feature in tumour suppression and immunity. The tumour suppressor p53 and interferon-α and -β (IFN-α/β) 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-α/β, accompanied by an increase in p53 protein level. IFN-α/β 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-α/β 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-α/β in tumour suppression and antiviral immunity, which may have therapeutic implications.
机译:快速消除不良细胞是抑制肿瘤和增强免疫力的重要特征。肿瘤抑制因子p53和干扰素-α和-β(IFN-α/β)分别对诱导癌细胞凋亡和抗病毒免疫应答至关重要,但对其相互关系了解甚少。在这里,我们显示p53基因的转录是由IFN-α/β诱导的,伴随着p53蛋白水平的增加。 IFN-α/β信号传导本身并不激活p53;相反,它有助于增强p53对应激信号的反应。我们展示了其中IFN-α/β诱导p53基因有助于抑制肿瘤的例子。此外,我们显示p53在病毒感染的细胞中被激活以引起凋亡反应,而p53对于宿主的抗病毒防御至关重要。我们的研究揭示了p53和IFN-α/β之间在肿瘤抑制和抗病毒免疫方面迄今尚未被认识的联系,这可能具有治疗意义。

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