Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

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

Download references

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

Authors

Corresponding author

Correspondence to Hirofumi Arakawa.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205459

Keywords

This article is cited by

Search

Quick links