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

Author

Listed:
  • Akinori Takaoka

    (University of Tokyo)

  • Sumio Hayakawa

    (University of Tokyo)

  • Hideyuki Yanai

    (University of Tokyo)

  • Dagmar Stoiber

    (University of Tokyo
    University of Vienna)

  • 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)

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.

Suggested Citation

  • Akinori Takaoka & Sumio Hayakawa & Hideyuki Yanai & Dagmar Stoiber & Hideo Negishi & Hideaki Kikuchi & Shigeru Sasaki & Kohzoh Imai & Tsukasa Shibue & Kenya Honda & Tadatsugu Taniguchi, 2003. "Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence," Nature, Nature, vol. 424(6948), pages 516-523, July.
    • Handle: RePEc:nat:nature:v:424:y:2003:i:6948:d:10.1038_nature01850
    DOI: 10.1038/nature01850
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    Cited by:

    1. Liping Zhuang & Xiantao Zeng & Zongguo Yang & Zhiqiang Meng, 2013. "Effect and Safety of Interferon for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-5, September.
    2. Junho Lee & Donggu Lee & Sean Lawler & Yangjin Kim, 2021. "Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural insights from a computational model," PLOS Computational Biology, Public Library of Science, vol. 17(2), pages 1-29, February.

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