Abstract
Interferon regulatory factors (IRFs) regulate transcription of interferon genes through DNA sequence-specific binding to these targets. Using a differential display method for examining gene expression in p53-defective cells infected with adenovirus containing wild-type p53, we found that expression of interferon regulatory factor 5 (IRF-5) mRNA was increased in the presence of exogenous p53. An electrophoretic mobility-shift assay showed that a potential p53 binding site (p53BS) detected in exon 2 of the IRF-5 gene could in fact bind to p53 protein. Moreover, a heterologous reporter assay revealed that the p53BS possessed p53-dependent transcriptional activity. Expression of IRF-5 was induced in p53+/+ cells (MCF7 and NHDF), but not inp53−/− cells (H1299) when DNA was damaged by γ-irradiation, UV-radiation, or adriamycin treatment in a wild-type p53-dependent manner. These results suggest that IRF-5 is a novel p53-target, and that it might mediate the p53-dependent immune response.
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Acknowledgements
We thank K Matsui for her excellent technical assistance. This work was supported in part by Grant #13216031 from the Ministry of Education, Culture, Sports, Science and Technology (to H Arakawa) and in part by ‘Research for the Future’ Program Grant #00L01402 from The Japan Society for the Promotion of Science (to Y Nakamura).
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Mori, T., Anazawa, Y., Iiizumi, M. et al. Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53. Oncogene 21, 2914–2918 (2002). https://doi.org/10.1038/sj.onc.1205459
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DOI: https://doi.org/10.1038/sj.onc.1205459
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