Skip to main content

IRF5

  • Reference work entry
  • First Online:
  • 348 Accesses

Synonyms

Interferon regulatory factor 5

Historical Background

The transcription factor interferon regulatory factor 5 (IRF5) is one of the newer members of the IRF family to be characterized. All cellular family members share a region of homology in the amino-terminus, encompassing a highly conserved DNA binding domain consisting of five tryptophan repeats. By crystallography, this region has been shown to bind to conserved elements, termed “interferon (IFN)-stimulated response elements” (ISREs), in the promoters of target genes (Chen et al. 2008) thereby exerting the biological effects of IRF5. Given the nomenclature of this family, it is not surprising that the first function of IRF5 to be recognized was its ability to regulate type I IFN gene expression (Barnes et al. 2001). However, unlike other IRF family members, such as IRF3 and IRF7, the activity of IRF5 is regulated in a virus-specific manner leading to the induction of distinct IFNA genes (Barnes et al. 2001).

Regulation of...

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Barnes BJ, Moore PA, Pitha PM. Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes. J Biol Chem. 2001;276:23382–90.

    Article  CAS  PubMed  Google Scholar 

  • Barnes BJ, Kellum MJ, Field AE, Pitha PM. Multiple regulatory domains of IRF-5 control activation, cellular localization and induction of chemokines that mediate T-lymphocyte recruitment. Mol Cell Biol. 2002;22:5721–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barnes BJ, Kellum MJ, Pinder KE, Frisancho JA, Pitha PM. IRF-5, a novel mediator of cell-cycle arrest and cell death. Cancer Res. 2003;63:6424–31.

    CAS  PubMed  Google Scholar 

  • Barnes BJ, Richards J, Mancl M, Hanash S, Beretta L, Pitha PM. Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection. J Biol Chem. 2004;279:45194–207.

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Lam SS, Srinath H, Jiang Z, Correia JJ, Schiffer CA, et al. Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5. Nat Struct Mol Biol. 2008;15:1213–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cheng TF, Brzostek S, Ando O, Van Scoy S, Kumar KP, Reich NC. Differential activation of IFN regulatory factor (IRF)-3 and IRF-5 transcription factors during viral infection. J Immunol. 2006;176:7462–70.

    Article  CAS  PubMed  Google Scholar 

  • Couzinet A, Tamura K, Chen HM, Nishimura K, Wang Z, Morishita Y, et al. A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis. Proc Natl Acad Sci USA. 2008;105:2556–61.

    Article  PubMed  PubMed Central  Google Scholar 

  • Feng D, Stone RC, Elonranta ML, Sangster-Guity N, Singh S, Nordmark G, et al. Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus. Arthritis Rheum. 2010;62:562–73.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Hu G, Barnes BJ. IRF-5 is a mediator of the death receptor-induced apoptotic signaling pathway. J Biol Chem. 2009;284:2767–77.

    Article  CAS  PubMed  Google Scholar 

  • Hu G, Mancl ME, Barnes BJ. Signaling through interferon regulatory factor-5 sensitizes p53-deficient tumor to DNA damage-induced apoptosis and cell death. Cancer Res. 2005;65:7403–12.

    Article  CAS  PubMed  Google Scholar 

  • Kozyrev SV, Alarcon-Riquelme ME. The genetics and biology of Irf5-mediated signaling in lupus. Autoimmunity. 2007;40:591–601.

    Article  CAS  PubMed  Google Scholar 

  • Krausgruber T, Saliba D, Ryzhakov G, Lanfrancotti A, Blazek K, Udalova IA. IRFS is required for late-phase TNF secretion by human dendritic cells. Blood. 2010;115:4421–30.

    Article  CAS  PubMed  Google Scholar 

  • Mancl ME, Hu G, Sangster-Guity N, Olshalsky SL, Hoops K, Fitzgerald-Bocarsly P, et al. Two distinct promoters regulate the alternative-spliced human Interferon regulatory factor-5 variants: multiple variants with distinct cell-type specific expression, localization, regulation and function. J Biol Chem. 2005;280:21078–90.

    Article  CAS  PubMed  Google Scholar 

  • Mori T, Anazawa Y, Iiizumi M, Fukuda S, Nakamura Y, Arakawa H. Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53. Oncogene. 2002;21:2914–8.

    Article  CAS  PubMed  Google Scholar 

  • Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis Rheum. 2008;58:2481–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Paun A, Reinert JT, Jiang Z, Medin C, Balkhi MY, Fitzgerald KA, Pitha PM. Functional charcterization of murine interferon regulatory factor 5(IRF-5) and its role in the innate antiviral response. J Biol Chem. 2008;283:14295–308.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Richez C, Yasuda K, Bonegio RG, Watkins AA, Aprahamian T, Busto P, et al. IFN regulatory factor 5 is required for disease development in the FcgammaRIIB−/−Yaa and FcgammaRIIB−/− mouse models of systemic lupus erythematosus. J Immunol. 2010;184:796–806.

    Article  CAS  PubMed  Google Scholar 

  • Savitsky DA, Yanai H, Tamura T, Taniguchi T, Honda K. Contribution of IRF5 in B cells to the development of murine SLE-like disease through its transcriptional control of the IgG2a locus. Proc Natl Acad Sci USA. 2010;107:10154–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schoenemeyer A, Barnes BJ, Mancl ME, Latz E, Goutagny N, Pitha PM, et al. The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. J Biol Chem. 2005;280:17005–12.

    Article  CAS  PubMed  Google Scholar 

  • Shin SH, Kim BH, Jang JJ, Suh KS, Kang GH. Identification of novel methylation markers in hepatocellular carcinoma using a methylation array. J Korean Med Sci. 2010;25:1152–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature. 2005;434:243–9.

    Article  CAS  PubMed  Google Scholar 

  • Yanai H, Chen HM, Inuzuka T, Kondo S, Mak TW, Takaoka A, et al. Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. Proc Natl Acad Sci USA. 2007;104:3402–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yasuda K, Richez C, Maciaszek JW, Agrawal N, Akira S, Marshak-Rothstein A, et al. Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for IL-6 production. J Immunol. 2007;178:6876–85.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Betsy J. Barnes .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Barnes, B.J. (2018). IRF5. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_307

Download citation

Publish with us

Policies and ethics