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.
Similar content being viewed by others
References
Driggers PH, Ennist DL, Gleason SL, Mak WH, Marks MS, Levi BZ, Flanagan JR, Appella E, Ozato K . 1990 Proc. Natl. Acad. Sci. USA 87: 3743–3747
el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B . 1992 Nat. Genet. 1: 45–49
el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler WE, Vogelstein B . 1993 Cell 75: 817–825
Furuhata T, Tokino T, Urano T, Nakamura Y . 1996 Oncogene 13: 1965–1970
Greenblatt MS, Bennett WP, Hollstein M, Harris CC . 1994 Cancer Res. 54: 4855–4878
Han HJ, Tokino T, Nakamura Y . 1998 Hum. Mol. Genet. 7: 1039–1046
Harada H, Taniguchi T, Tanaka N . 1998 Biochimie 80: 641–650
Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ . 1993 Cell 75: 805–816
Kim T, Kim TY, Song YH, Min IM, Yim J, Kim TK . 1999 J. Biol. Chem. 274: 30686–30689
Levine AJ . 1997 Cell 88: 323–331
Matsuyama T, Grossman A, Mittrucker HW, Siderovski DP, Kiefer F, Kawakami T, Richardson CD, Taniguchi T, Yoshinaga SK, Mak TW . 1995 Nucl. Acids Res. 23: 2127–2136
Miyashita T, Reed JC . 1995 Cell 80: 293–299
Ng CC, Koyama K, Okamura S, Kondoh H, Takei Y, Nakamura Y . 1999 Genes Chrom. Cancer 26: 329–335
Nishimori H, Shiratsuchi T, Urano T, Kimura Y, Kiyono K, Tatsumi K, Yoshida S, Ono M, Kuwano M, Nakamura Y, Tokino T . 1997 Oncogene 15: 2145–2150
Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y, Taya Y . 2000 Cell 102: 849–862
Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y, Monden M, Nakamura Y . 2001 Mol. Cell 8: 85–94
Pitha PM, Au WC, Lowther W, Juang YT, Schafer SL, Burysek L, Hiscott J, Moore PA . 1998 Biochimie 80: 651–658
Shiraishi K, Fukuda S, Mori T, Matsuda K, Yamaguchi T, Tanikawa C, Ogawa M, Nakamura Y, Arakawa H . 2000 Cancer Res. 60: 3722–3726
Takei Y, Ishikawa S, Tokino T, Muto T, Nakamura Y . 1998 Genes Chrom. Cancer 23: 1–9
Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, Matsuyama T, Mak TW, Taki S, Taniguchi T . 1995 Nature 376: 596–599
Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, Takei Y, Nakamura Y . 2000 Nature 404: 42–49
Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, Lamphier MS, Aizawa S, Mak TW, Taniguchi T . 1994 Cell 77: 829–839
Tanaka N, Ishihara M, Lamphier MS, Nozawa H, Matsuyama T, Mak TW, Aizawa S, Tokino T, Oren M, Taniguchi T . 1996 Nature 382: 816–818
Tokino T, Thiagalingam S, el-Deiry WS, Waldman T, Kinzler KW, Vogelstein B . 1994 Hum. Mol. Genet. 3: 1537–1542
Urano T, Nishimori H, Han H, Furuhata T, Kimura Y, Nakamura Y, Tokino T . 1997 Cancer Res. 57: 3281–3287
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).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205459
- Springer Nature Limited
Keywords
This article is cited by
-
Translating p53-based therapies for cancer into the clinic
Nature Reviews Cancer (2024)
-
Regulation of immunological tolerance by the p53-inhibitor iASPP
Cell Death & Disease (2023)
-
Crosstalk between microglia and patient-derived glioblastoma cells inhibit invasion in a three-dimensional gelatin hydrogel model
Journal of Neuroinflammation (2020)
-
Immunological impact of cell death signaling driven by radiation on the tumor microenvironment
Nature Immunology (2020)
-
The Role of Interferon Regulatory Factor 5 in Macrophage Inflammation During Osteoarthritis
Inflammation (2019)