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Gene Review

IRF1  -  interferon regulatory factor 1

Homo sapiens

Synonyms: IRF-1, Interferon regulatory factor 1, MAR
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Disease relevance of IRF1


Psychiatry related information on IRF1

  • The high permissiveness of the cured cells for the replicon was abolished by transgenic supplementation of IRF-1 expression [6].
  • The IRF-family may be examples of transcription factors which can selectively modulate several sets of genes depending on the cell type and/or nature of the cellular stimuli, so as to evoke host defense mechanisms against infection and oncogenesis [7].
  • The slope of the psychometric acuity function remained essentially constant for different threshold acuities when acuity was scaled logarithmically (log MAR), but varied with the threshold when inverse Snellen (MAR) and Snell-Sterling scales were used [8].

High impact information on IRF1

  • Following the initial identification of two structurally related members, IRF-1 and IRF-2, seven additional members have now been reported [9].
  • A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition [10].
  • Deletion mutants indicate that multiple AT-rich sequences, if contained in a minimal approximately 350 bp MAR fragment, can lead to efficient binding of ARBP [11].
  • Together, these features suggest a basis for the occurrence of GAAA repeats within IRF response elements and provide clues to the assembly of the higher-order interferon-beta enhancesome [12].
  • The IRF family is characterized by a unique 'tryptophan cluster' DNA-binding region [12].

Chemical compound and disease context of IRF1


Biological context of IRF1

  • The key pathways involved in mediating this septic organ dysfunction (cell adhesion molecule expression, inducible nitric-oxide synthase induction, and apoptosis) are known to be regulated by transcription factors STAT1, IRF1, and NF-kappaB [1].
  • In contrast, transfection of U937 cells with reporter vectors containing p53 and IRF1 promoters with mutated IPCS sites resulted in a 4-fold reduction in the constitutive expression of those two genes [18].
  • (v) Recombinant IRF1, although unable to bind to an NF-kappaB consensus sequence, competes with NF-kappaB proteins for binding to the MMP-9 promoter [19].
  • CONCLUSION: These results suggested that among IFNG and related genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in Japanese children [20].
  • We conclude that a high ratio of IRF1/IRF2 expression may be associated with good cytogenetic and molecular response to IFN-alpha in CML [21].

Anatomical context of IRF1


Associations of IRF1 with chemical compounds


Physical interactions of IRF1

  • We show here that ICSBP forms a complex with IRF-1 or IRF-2 both in vivo and in vitro and, in the presence or absence of the target DNA, with the IFN-stimulated response element (ISRE) [28].
  • The inhibitory effects of OAS were accompanied by a reduction in PRL-inducible Stat1 (signal transducer and activator of transcription 1) DNA binding activity at the IRF-1 GAS (interferon-gamma-activated sequence) element [29].
  • With B9 cells, there was no IRF-1 binding but instead strong constitutive binding of the IRF-2 repressor, indicating that binding of IRF-1 to DNA is an important regulatory step [30].
  • Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B [19].
  • Thus, in contrast to the known synergism between IRF1 and NF-kappaB, our data identify a novel role for IRF1 as a competitive inhibitor of NF-kappaB binding to the particular MMP-9 promoter context [19].

Enzymatic interactions of IRF1

  • The growth rates negatively correlated with levels of both IRF-1 expression and constitutively phosphorylated Jak1 [31].

Regulatory relationships of IRF1


Other interactions of IRF1


Analytical, diagnostic and therapeutic context of IRF1

  • Both reporter and electrophoretic mobility shift assays demonstrated a 5-19-fold increase in activation of transcription factors STAT1, IRF1, and NF-kappaB in response to incubation with human septic serum [1].
  • In bronchoalveolar lavage (BAL) cells obtained from 10 of 10 tuberculosis patients 10 +/- 2 days post-antituberculosis treatment, there was no detectable STAT-1 or IRF-1 DNA-binding activity [37].
  • Duodenal biopsies were taken from children with untreated CD and control children, and analyzed for IRF-1 by Southern blotting of reverse-transcriptase PCR products and Western blotting [38].
  • The effect of gliadin stimulation on IRF-1 induction was investigated in an ex vivo organ culture of treated CD biopsies [38].
  • Protein/DNA array analysis revealed significant up-regulation of both IRF-1 and p53 protein in nuclear extracts [39].


  1. Human serum from patients with septic shock activates transcription factors STAT1, IRF1, and NF-kappaB and induces apoptosis in human cardiac myocytes. Kumar, A., Kumar, A., Michael, P., Brabant, D., Parissenti, A.M., Ramana, C.V., Xu, X., Parrillo, J.E. J. Biol. Chem. (2005) [Pubmed]
  2. Alterations in IRF1/IRF2 expression in acute myelogenous leukemia. Preisler, H.D., Perambakam, S., Li, B., Hsu, W.T., Venugopal, P., Creech, S., Sivaraman, S., Tanaka, N. Am. J. Hematol. (2001) [Pubmed]
  3. Retinoic acid activates interferon regulatory factor-1 gene expression in myeloid cells. Matikainen, S., Ronni, T., Hurme, M., Pine, R., Julkunen, I. Blood (1996) [Pubmed]
  4. Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors. Lubyova, B., Pitha, P.M. J. Virol. (2000) [Pubmed]
  5. A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation. Chang, T.L., Mosoian, A., Pine, R., Klotman, M.E., Moore, J.P. J. Virol. (2002) [Pubmed]
  6. Regulation of hepatitis C virus replication by interferon regulatory factor 1. Kanazawa, N., Kurosaki, M., Sakamoto, N., Enomoto, N., Itsui, Y., Yamashiro, T., Tanabe, Y., Maekawa, S., Nakagawa, M., Chen, C.H., Kakinuma, S., Oshima, S., Nakamura, T., Kato, T., Wakita, T., Watanabe, M. J. Virol. (2004) [Pubmed]
  7. The role of interferon regulatory factors in the interferon system and cell growth control. Harada, H., Taniguchi, T., Tanaka, N. Biochimie (1998) [Pubmed]
  8. Variations in the slope of the psychometric acuity function with acuity threshold and scale. Horner, D.G., Paul, A.D., Katz, B., Bedell, H.E. American journal of optometry and physiological optics. (1985) [Pubmed]
  9. IRF family of transcription factors as regulators of host defense. Taniguchi, T., Ogasawara, K., Takaoka, A., Tanaka, N. Annu. Rev. Immunol. (2001) [Pubmed]
  10. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Dickinson, L.A., Joh, T., Kohwi, Y., Kohwi-Shigematsu, T. Cell (1992) [Pubmed]
  11. A matrix/scaffold attachment region binding protein: identification, purification, and mode of binding. von Kries, J.P., Buhrmester, H., Strätling, W.H. Cell (1991) [Pubmed]
  12. Structure of IRF-1 with bound DNA reveals determinants of interferon regulation. Escalante, C.R., Yie, J., Thanos, D., Aggarwal, A.K. Nature (1998) [Pubmed]
  13. Retinoic acid is able to induce interferon regulatory factor 1 in squamous carcinoma cells via a STAT-1 independent signalling pathway. Percario, Z.A., Giandomenico, V., Fiorucci, G., Chiantore, M.V., Vannucchi, S., Hiscott, J., Affabris, E., Romeo, G. Cell Growth Differ. (1999) [Pubmed]
  14. IFN-beta induces serine phosphorylation of Stat-1 in Ewing's sarcoma cells and mediates apoptosis via induction of IRF-1 and activation of caspase-7. Sancéau, J., Hiscott, J., Delattre, O., Wietzerbin, J. Oncogene (2000) [Pubmed]
  15. Interferon regulatory factor-1 and -2 expression in human melanoma specimens. Lowney, J.K., Boucher, L.D., Swanson, P.E., Doherty, G.M. Ann. Surg. Oncol. (1999) [Pubmed]
  16. Posttranscriptional inhibition of gene expression by Mycobacterium tuberculosis offsets transcriptional synergism with IFN-gamma and posttranscriptional up-regulation by IFN-gamma. Qiao, Y., Prabhakar, S., Canova, A., Hoshino, Y., Weiden, M., Pine, R. J. Immunol. (2004) [Pubmed]
  17. Nuclear factor kappa B is involved in lipopolysaccharide-stimulated induction of interferon regulatory factor-1 and GAS/GAF DNA-binding in human umbilical vein endothelial cells. Liu, L., Paul, A., MacKenzie, C.J., Bryant, C., Graham, A., Plevin, R. Br. J. Pharmacol. (2001) [Pubmed]
  18. Identification of a novel transcriptional regulatory element common to the p53 and interferon regulatory factor 1 genes. Lallemand, C., Bayat-Sarmadi, M., Blanchard, B., Tovey, M.G. J. Biol. Chem. (1997) [Pubmed]
  19. Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B. Sancéau, J., Boyd, D.D., Seiki, M., Bauvois, B. J. Biol. Chem. (2002) [Pubmed]
  20. Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood atopic asthma. Nakao, F., Ihara, K., Kusuhara, K., Sasaki, Y., Kinukawa, N., Takabayashi, A., Nishima, S., Hara, T. J. Allergy Clin. Immunol. (2001) [Pubmed]
  21. Expression of interferon regulatory factor (IRF) genes and response to interferon-alpha in chronic myeloid leukaemia. Hochhaus, A., Yan, X.H., Willer, A., Hehlmann, R., Gordon, M.Y., Goldman, J.M., Melo, J.V. Leukemia (1997) [Pubmed]
  22. MEK-ERK signaling is involved in interferon-gamma-induced death of oligodendroglial progenitor cells. Horiuchi, M., Itoh, A., Pleasure, D., Itoh, T. J. Biol. Chem. (2006) [Pubmed]
  23. Human cancer cell lines express a negative transcriptional regulator of the interferon regulatory factor family of DNA binding proteins. Petricoin, E., David, M., Fang, H., Grimley, P., Larner, A.C., Vande Pol, S. Mol. Cell. Biol. (1994) [Pubmed]
  24. Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells. Oshima, S., Nakamura, T., Namiki, S., Okada, E., Tsuchiya, K., Okamoto, R., Yamazaki, M., Yokota, T., Aida, M., Yamaguchi, Y., Kanai, T., Handa, H., Watanabe, M. Mol. Cell. Biol. (2004) [Pubmed]
  25. Reactive oxygen species mediate virus-induced STAT activation: role of tyrosine phosphatases. Liu, T., Castro, S., Brasier, A.R., Jamaluddin, M., Garofalo, R.P., Casola, A. J. Biol. Chem. (2004) [Pubmed]
  26. Interferon regulatory factor-1 regulates reconstituted extracellular matrix (rECM)-mediated apoptosis in human mammary epithelial cells. Bowie, M.L., Troch, M.M., Delrow, J., Dietze, E.C., Bean, G.R., Ibarra, C., Pandiyan, G., Seewaldt, V.L. Oncogene (2007) [Pubmed]
  27. Interaction between the interferon signaling pathway and the human glucocorticoid receptor gene 1A promoter. Nunez, B.S., Geng, C.D., Pedersen, K.B., Millro-Macklin, C.D., Vedeckis, W.V. Endocrinology (2005) [Pubmed]
  28. Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family. Bovolenta, C., Driggers, P.H., Marks, M.S., Medin, J.A., Politis, A.D., Vogel, S.N., Levy, D.E., Sakaguchi, K., Appella, E., Coligan, J.E. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  29. Association of 2',5'-oligoadenylate synthetase with the prolactin (PRL) receptor: alteration in PRL-inducible stat1 (signal transducer and activator of transcription 1) signaling to the IRF-1 (interferon-regulatory factor 1) promoter. McAveney, K.M., Book, M.L., Ling, P., Chebath, J., Yu-Lee, L. Mol. Endocrinol. (2000) [Pubmed]
  30. Induction by interleukin-6 of interferon regulatory factor 1 (IRF-1) gene expression through the palindromic interferon response element pIRE and cell type-dependent control of IRF-1 binding to DNA. Harroch, S., Revel, M., Chebath, J. EMBO J. (1994) [Pubmed]
  31. Growth arrest of epithelial cells during measles virus infection is caused by upregulation of interferon regulatory factor 1. Yokota, S., Okabayashi, T., Yokosawa, N., Fujii, N. J. Virol. (2004) [Pubmed]
  32. Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system. Harada, H., Takahashi, E., Itoh, S., Harada, K., Hori, T.A., Taniguchi, T. Mol. Cell. Biol. (1994) [Pubmed]
  33. Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells. Stang, M.T., Armstrong, M.J., Watson, G.A., Sung, K.Y., Liu, Y., Ren, B., Yim, J.H. Oncogene (2007) [Pubmed]
  34. Two distinct gamma interferon-inducible promoters of the major histocompatibility complex class II transactivator gene are differentially regulated by STAT1, interferon regulatory factor 1, and transforming growth factor beta. Piskurich, J.F., Linhoff, M.W., Wang, Y., Ting, J.P. Mol. Cell. Biol. (1999) [Pubmed]
  35. Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages. Lehtonen, A., Matikainen, S., Julkunen, I. J. Immunol. (1997) [Pubmed]
  36. Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes. Barnes, B.J., Moore, P.A., Pitha, P.M. J. Biol. Chem. (2001) [Pubmed]
  37. Recombinant gamma interferon stimulates signal transduction and gene expression in alveolar macrophages in vitro and in tuberculosis patients. Condos, R., Raju, B., Canova, A., Zhao, B.Y., Weiden, M., Rom, W.N., Pine, R. Infect. Immun. (2003) [Pubmed]
  38. Enhanced expression of interferon regulatory factor-1 in the mucosa of children with celiac disease. Salvati, V.M., MacDonald, T.T., del Vecchio Blanco, G., Mazzarella, G., Monteleone, I., Vavassori, P., Auricchio, S., Pallone, F., Troncone, R., Monteleone, G. Pediatr. Res. (2003) [Pubmed]
  39. Peptide YY Reverses TNF-alpha Induced Transcription Factor Binding of Interferon Regulatory Factor-1 and p53 in Pancreatic Acinar Cells. Rizvi, I.A., Robinson, K., McFadden, D.W., Riggs, D.R., Jackson, B.J., Vona-Davis, L. J. Surg. Res. (2006) [Pubmed]
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