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

Akinori Takaoka, Sumio Hayakawa, Hideyuki Yanai, Dagmar Stoiber, Hideo Negishi, Hideaki Kikuchi, Shigeru Sasaki, Kohzoh Imai, Tsukasa Shibue, Kenya Honda and Tadatsugu Taniguchi ()
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Akinori Takaoka: University of Tokyo
Sumio Hayakawa: University of Tokyo
Hideyuki Yanai: University of Tokyo
Dagmar Stoiber: University of Tokyo
Hideo Negishi: University of Tokyo
Hideaki Kikuchi: University of Tokyo
Shigeru Sasaki: Sapporo Medical University School of Medicine
Kohzoh Imai: Sapporo Medical University School of Medicine
Tsukasa Shibue: University of Tokyo
Kenya Honda: University of Tokyo
Tadatsugu Taniguchi: University of Tokyo

Nature, 2003, vol. 424, issue 6948, 516-523

Abstract: Abstract 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.

Date: 2003
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DOI: 10.1038/nature01850

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