@article{2f8723870b0a4cbd9819342992f326a0,
title = "Integration of interferon-α/β signalling to p53 responses in tumour suppression and antiviral defence",
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.",
author = "Akinori Takaoka and Sumio Hayakawa and Hideyuki Yanai and Dagmar Stoiber and Hideo Negishi and Hideaki Kikuchi and Shigeru Sasaki and Kohzoh Imai and Tsukasa Shibue and Kenya Honda and Tadatsugu Taniguchi",
note = "Funding Information: Acknowledgements WethankY.Tayaforanti-p53-P-Ser15antibody;Y.HirabayashiandT.Inoue for p532/2 mice; T. Kiyono for pLRHL-16E6; C. Westphal for ATM/p53 deficient MEFs; K. Segawa for pSVp53c17 and pLSVNc-9; T. Nakajima for adenovirus 2 E1A 12S cDNA; Toray Co., Ltd for recombinant human and mouse IFN-b; J. Vilcek and E. Barsoumian for critical reading of the manuscript; H. zur Hausen, F. Melchers, Y. Taya and N. Tanaka for advice; and T. Yokochi for technical assistance. This work was supported in part by a grant for Advanced Research on Cancer from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Grants-in-Aid from the Ministry of Education, Science and Culture (Scientific Research on Priority Areas), grants of the Virtual Research Institute of Ageing of Nippon Boehringer Ingelheim, the Welfide Medicinal Research Foundation, Kanae Foundation for Life & SocioMedical Science, and Senri Life Science Foundation. D.S. was a postdoctoral fellow, supported by the Japan Society for the Promotion of Science.",
year = "2003",
month = jul,
day = "31",
doi = "10.1038/nature01850",
language = "English",
volume = "424",
pages = "516--523",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "6948",
}