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: Journal article (peer-reviewed)Journal article

782 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 - 31 Jul 2003
Externally publishedYes

Keywords

  • Animals
  • Apoptosis
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins/metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Interferon-alpha/metabolism
  • Interferon-beta/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms/immunology
  • RNA, Messenger/genetics
  • Response Elements/genetics
  • Signal Transduction
  • Transcription Factors/metabolism
  • Transcription, Genetic/genetics
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53/biosynthesis
  • Vesicular stomatitis Indiana virus/immunology

ASJC Scopus subject areas

  • Multidisciplinary

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