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, Tadatsugu Taniguchi

Research output: Contribution to journalArticle

634 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)516-523
Number of pages8
JournalNature
Volume424
Issue number6948
DOIs
Publication statusPublished - 2003 Jul 31
Externally publishedYes

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Interferons
Antiviral Agents
p53 Genes
Neoplasms
Immunity
Apoptosis
Proteins
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., ... Taniguchi, T. (2003). Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence. Nature, 424(6948), 516-523. https://doi.org/10.1038/nature01850

Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence. / Takaoka, Akinori; Hayakawa, Sumio; Yanai, Hideyuki; Stoiber, Dagmar; Negishi, Hideo; Kikuchi, Hideaki; Sasaki, Shigeru; Imai, Kohzoh; Shibue, Tsukasa; Honda, Kenya; Taniguchi, Tadatsugu.

In: Nature, Vol. 424, No. 6948, 31.07.2003, p. 516-523.

Research output: Contribution to journalArticle

Takaoka, A, Hayakawa, S, Yanai, H, Stoiber, D, Negishi, H, Kikuchi, H, Sasaki, S, Imai, K, Shibue, T, Honda, K & Taniguchi, T 2003, 'Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence', Nature, vol. 424, no. 6948, pp. 516-523. https://doi.org/10.1038/nature01850
Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H et al. Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence. Nature. 2003 Jul 31;424(6948):516-523. https://doi.org/10.1038/nature01850
Takaoka, Akinori ; Hayakawa, Sumio ; Yanai, Hideyuki ; Stoiber, Dagmar ; Negishi, Hideo ; Kikuchi, Hideaki ; Sasaki, Shigeru ; Imai, Kohzoh ; Shibue, Tsukasa ; Honda, Kenya ; Taniguchi, Tadatsugu. / Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence. In: Nature. 2003 ; Vol. 424, No. 6948. pp. 516-523.
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