Takaoka Akinori, Hayakawa Sumio, Yanai Hideyuki, Stoiber Dagmar, Negishi Hideo, Kikuchi Hideaki, Sasaki Shigeru, Imai Kohzoh, Shibue Tsukasa, Honda Kenya, Taniguchi Tadatsugu
Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature. 2003 Jul 31;424(6948):516-23. doi: 10.1038/nature01850.
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.
迅速清除不良细胞是肿瘤抑制和免疫的一个重要特征。肿瘤抑制因子p53以及α和β干扰素（IFN-α/β）分别对于诱导癌细胞凋亡和抗病毒免疫反应至关重要，但它们之间的相互关系却鲜为人知。在此我们表明，p53基因的转录由IFN-α/β诱导，同时p53蛋白水平升高。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IFN-α/β诱导p53基因有助于肿瘤抑制的实例。此外，我们表明p53在病毒感染的细胞中被激活以引发凋亡反应，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p53与IFN-α/β在肿瘤抑制和抗病毒免疫方面迄今未被认识到的联系，这可能具有治疗意义。
