Integration of interferon-alpha/beta 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

doi:10.1038/nature01850

Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence

Nature. 2003 Jul 31;424(6948):516-23. doi: 10.1038/nature01850.

Authors

Akinori Takaoka¹, Sumio Hayakawa, Hideyuki Yanai, Dagmar Stoiber, Hideo Negishi, Hideaki Kikuchi, Shigeru Sasaki, Kohzoh Imai, Tsukasa Shibue, Kenya Honda, Tadatsugu Taniguchi

Affiliation

¹ Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

PMID: 12872134
DOI: 10.1038/nature01850

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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*
Neoplasms / pathology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Response Elements / genetics
Signal Transduction*
Transcription Factors / metabolism
Transcription, Genetic / genetics
Transcriptional Activation
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / biosynthesis*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
Vesicular stomatitis Indiana virus / immunology*
Vesicular stomatitis Indiana virus / physiology

Substances

DNA-Binding Proteins
IRF9 protein, human
Interferon-Stimulated Gene Factor 3
Interferon-Stimulated Gene Factor 3, gamma Subunit
Interferon-alpha
Isgf3g protein, mouse
RNA, Messenger
Transcription Factors
Tumor Suppressor Protein p53
Interferon-beta