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

被引:729
作者
Takaoka, A
Hayakawa, S
Yanai, H
Stoiber, D
Negishi, H
Kikuchi, H
Sasaki, S
Imai, K
Shibue, T
Honda, K
Taniguchi, T
机构
[1] Univ Tokyo, Fac Med, Dept Immunol, Bunkyo Ku, Tokyo 1130033, Japan
[2] Univ Tokyo, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan
[3] Sapporo Med Univ, Sch Med, Dept Internal Med 1, Chuo Ku, Sapporo, Hokkaido 0608556, Japan
基金
日本学术振兴会;
关键词
D O I
10.1038/nature01850
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:516 / 523
页数:8
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