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Gene Review

Irf1  -  interferon regulatory factor 1

Mus musculus

Synonyms: AU020929, IRF-1, Interferon regulatory factor 1, Irf-1
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Disease relevance of Irf1

  • In contrast, mice deficient for IRF1 were not able to produce nitric oxide, but they efficiently controlled Listeria in vivo and in vitro [1].
  • Our results suggest that IFNgamma gene therapy maybe effective in malignant diseases for which DNA tumor viruses are etiologic agents and that antitumor actions of IRF-1/ICSBP can be exploited therapeutically to circumvent adverse clinical effects associated with IFN therapy [2].
  • DSS or TNBS led to a dramatic increase in lethality and colitis severity in IRF-1 KO compared with WT mice [3].
  • These data indicate that different virulence factors from P. aeruginosa induce pulmonary inflammation in vivo and that IRF-1 is involved in some of the cytokine responses to LPS and ETA [4].
  • IgG and C3 deposition as well as glomerulonephritis were decreased in IRF-1(-/-) mice at 26 wk of age compared to the IRF-1(+/+) mice [5].

High impact information on Irf1

  • The transcriptional activator interferon regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the interferon (IFN) system and of cell growth [6].
  • Here we report that embryonic fibroblasts (EFs) from mice with a null mutation in the IRF-1 gene (IRF-1-/- mice) can be transformed by expression of an activated c-Ha-ras oncogene [6].
  • Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1 [6].
  • The transformed phenotype of ras-expressing IRF-1-/- EFs could be suppressed by the expression of the IRF-1 cDNA [6].
  • A profound reduction of TCR alpha beta+CD4-CD8+ T cells in IRF-1-deficient mice, with a thymocyte developmental defect, reveals a critical role for IRF-1 in T cell development [7].

Chemical compound and disease context of Irf1


Biological context of Irf1

  • In addition, overexpression of a growth-suppressive transcription factor, Irf1, a putative key molecule in the p53-independent pathway after DNA damage, was also observed, although the relation to the loss of G1 arrest could not be elucidated [12].
  • Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon [13].
  • Interferon regulatory factor-1 up-regulates angiotensin II type 2 receptor and induces apoptosis [14].
  • Complex formation of the interferon (IFN) consensus sequence-binding protein with IRF-1 is essential for murine macrophage IFN-gamma-induced iNOS gene expression [15].
  • Furthermore, we observed using reverse transcription-polymerase chain reaction that the IRF-1 mRNA expression was more abundant in confluent cells than growing cells, whereas IRF-2 expression did not change with R3T3 cell growth [16].

Anatomical context of Irf1


Associations of Irf1 with chemical compounds


Physical interactions of Irf1


Regulatory relationships of Irf1


Other interactions of Irf1


Analytical, diagnostic and therapeutic context of Irf1


  1. Crucial role of interferon consensus sequence binding protein, but neither of interferon regulatory factor 1 nor of nitric oxide synthesis for protection against murine listeriosis. Fehr, T., Schoedon, G., Odermatt, B., Holtschke, T., Schneemann, M., Bachmann, M.F., Mak, T.W., Horak, I., Zinkernagel, R.M. J. Exp. Med. (1997) [Pubmed]
  2. Interferon-gamma induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors. Egwuagu, C.E., Li, W., Yu, C.R., Che Mei Lin, M., Chan, C.C., Nakamura, T., Chepelinsky, A.B. Oncogene (2006) [Pubmed]
  3. Frontline: interferon regulatory factor-1 as a protective gene in intestinal inflammation: role of TCR gamma delta T cells and interleukin-18-binding protein. Siegmund, B., Sennello, J.A., Lehr, H.A., Senaldi, G., Dinarello, C.A., Fantuzzi, G. Eur. J. Immunol. (2004) [Pubmed]
  4. Pulmonary inflammation induced by Pseudomonas aeruginosa lipopolysaccharide, phospholipase C, and exotoxin A: role of interferon regulatory factor 1. Wieland, C.W., Siegmund, B., Senaldi, G., Vasil, M.L., Dinarello, C.A., Fantuzzi, G. Infect. Immun. (2002) [Pubmed]
  5. Interferon regulatory factor-1 gene deletion decreases glomerulonephritis in MRL/lpr mice. Reilly, C.M., Olgun, S., Goodwin, D., Gogal, R.M., Santo, A., Romesburg, J.W., Ansar Ahmed, S., Gilkeson, G.S. Eur. J. Immunol. (2006) [Pubmed]
  6. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Tanaka, N., Ishihara, M., Kitagawa, M., Harada, H., Kimura, T., Matsuyama, T., Lamphier, M.S., Aizawa, S., Mak, T.W., Taniguchi, T. Cell (1994) [Pubmed]
  7. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Matsuyama, T., Kimura, T., Kitagawa, M., Pfeffer, K., Kawakami, T., Watanabe, N., Kündig, T.M., Amakawa, R., Kishihara, K., Wakeham, A. Cell (1993) [Pubmed]
  8. 17beta-estradiol downregulates interferon regulatory factor-1 in murine splenocytes. Lengi, A.J., Phillips, R.A., Karpuzoglu, E., Ahmed, S.A. J. Mol. Endocrinol. (2006) [Pubmed]
  9. Role of IFN regulatory factor-1 and IL-12 in immunological resistance to pathogenesis of N-methyl-N-nitrosourea-induced T lymphoma. Liu, J., Xiang, Z., Ma, X. J. Immunol. (2004) [Pubmed]
  10. Altered phenotype of dextran sulfate sodium colitis in interferon regulatory factor-1 knock-out mice. Mannick, E.E., Cote, R.L., Schurr, J.R., Krowicka, H.S., Sloop, G.D., Zapata-Velandia, A., Correa, H., Ruiz, B., Horswell, R., Lentz, J.J., Byrne, P., Gastanaduy, M.M., Hornick, C.A., Liu, Z. J. Gastroenterol. Hepatol. (2005) [Pubmed]
  11. Prevention of lymphocytic thyroiditis in iodide-treated non-obese diabetic mice lacking interferon regulatory factor-1. Tani, J., Mori, K., Hoshikawa, S., Nakazawa, T., Satoh, J., Nakagawa, Y., Ito, S., Yoshida, K. Eur. J. Endocrinol. (2002) [Pubmed]
  12. Abrogation of G1 arrest after DNA damage is associated with constitutive overexpression of Mdm2, Cdk4, and Irf1 mRNAs in the BALB/c 3T3 A31 variant 1-1 clone. Nozaki, T., Masutani, M., Sugimura, T., Takato, T., Wakabayashi, K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  13. Interferon regulatory factor 1 is required for mouse Gbp gene activation by gamma interferon. Briken, V., Ruffner, H., Schultz, U., Schwarz, A., Reis, L.F., Strehlow, I., Decker, T., Staeheli, P. Mol. Cell. Biol. (1995) [Pubmed]
  14. Interferon regulatory factor-1 up-regulates angiotensin II type 2 receptor and induces apoptosis. Horiuchi, M., Yamada, T., Hayashida, W., Dzau, V.J. J. Biol. Chem. (1997) [Pubmed]
  15. Complex formation of the interferon (IFN) consensus sequence-binding protein with IRF-1 is essential for murine macrophage IFN-gamma-induced iNOS gene expression. Xiong, H., Zhu, C., Li, H., Chen, F., Mayer, L., Ozato, K., Unkeless, J.C., Plevy, S.E. J. Biol. Chem. (2003) [Pubmed]
  16. The growth-dependent expression of angiotensin II type 2 receptor is regulated by transcription factors interferon regulatory factor-1 and -2. Horiuchi, M., Koike, G., Yamada, T., Mukoyama, M., Nakajima, M., Dzau, V.J. J. Biol. Chem. (1995) [Pubmed]
  17. Cytokine-inducible CD40 expression in human endothelial cells is mediated by interferon regulatory factor-1. Wagner, A.H., Gebauer, M., Pollok-Kopp, B., Hecker, M. Blood (2002) [Pubmed]
  18. Impaired IFN-gamma production in IFN regulatory factor-1 knockout mice during endotoxemia is secondary to a loss of both IL-12 and IL-12 receptor expression. Salkowski, C.A., Thomas, K.E., Cody, M.J., Vogel, S.N. J. Immunol. (2000) [Pubmed]
  19. Interferon regulatory factor 1 is an essential and direct transcriptional activator for interferon {gamma}-induced RANTES/CCl5 expression in macrophages. Liu, J., Guan, X., Ma, X. J. Biol. Chem. (2005) [Pubmed]
  20. The lipopolysaccharide-triggered mesangial transcriptome: Evaluating the role of interferon regulatory factor-1. Fu, Y., Xie, C., Yan, M., Li, Q., Joh, J.W., Lu, C., Mohan, C. Kidney Int. (2005) [Pubmed]
  21. Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. Ruiz, P.A., Haller, D. J. Nutr. (2006) [Pubmed]
  22. Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter. Maruyama, S., Sumita, K., Shen, H., Kanoh, M., Xu, X., Sato, M., Matsumoto, M., Shinomiya, H., Asano, Y. J. Immunol. (2003) [Pubmed]
  23. Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1. Brucet, M., Marqués, L., Sebastián, C., Lloberas, J., Celada, A. Genes Immun. (2004) [Pubmed]
  24. Nramp1 functionality increases inducible nitric oxide synthase transcription via stimulation of IFN regulatory factor 1 expression. Fritsche, G., Dlaska, M., Barton, H., Theurl, I., Garimorth, K., Weiss, G. J. Immunol. (2003) [Pubmed]
  25. Conserved high-affinity NF-kappa B binding site in the interferon regulatory factor-1 promoter is not occupied by NF-kappa B in vivo and is transcriptionally inactive. Rein, T., Schreck, R., Willenbrink, W., Neubert, W.J., Zorbas, H., Bäuerle, P.A. J. Inflamm. (1995) [Pubmed]
  26. Role of interferon regulatory factor-1 in double-stranded RNA-induced iNOS expression by mouse islets. Blair, L.A., Maggi, L.B., Scarim, A.L., Corbett, J.A. J. Biol. Chem. (2002) [Pubmed]
  27. Interferon regulatory factor-1 down-regulates cytokine-induced IP-10 expression in pancreatic islets. Baker, M.S., Chen, X., Rotramel, A.R., Nelson, J.J., Kaufman, D.B. Surgery (2003) [Pubmed]
  28. The role of interferon regulatory factor-1 in cytokine-induced mRNA expression and cell death in murine pancreatic beta-cells. Pavlovic, D., Chen, M.C., Gysemans, C.A., Mathieu, C., Eizirik, D.L. Eur. Cytokine Netw. (1999) [Pubmed]
  29. Interaction of interferon regulatory factor-1 and nuclear factor kappaB during activation of inducible nitric oxide synthase transcription. Saura, M., Zaragoza, C., Bao, C., McMillan, A., Lowenstein, C.J. J. Mol. Biol. (1999) [Pubmed]
  30. Inhibition of inducible nitric-oxide synthase expression by (5R)-5-hydroxytriptolide in interferon-gamma- and bacterial lipopolysaccharide-stimulated macrophages. Zhou, R., Zheng, S.X., Tang, W., He, P.L., Li, X.Y., Yang, Y.F., Li, Y.C., Geng, J.G., Zuo, J.P. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  31. The transcription factor interferon regulatory factor-1 mediates liver damage during ischemia-reperfusion injury. Tsung, A., Stang, M.T., Ikeda, A., Critchlow, N.D., Izuishi, K., Nakao, A., Chan, M.H., Jeyabalan, G., Yim, J.H., Geller, D.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  32. Induction of transcription factor interferon regulatory factor-1 by interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) in FRTL-5 cells. Mori, K., Stone, S., Khaodhiar, L., Braverman, L.E., DeVito, W.J. J. Cell. Biochem. (1999) [Pubmed]
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