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Gene Review

IRF2  -  interferon regulatory factor 2

Homo sapiens

Synonyms: IRF-2, Interferon regulatory factor 2
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Disease relevance of IRF2


High impact information on IRF2

  • Following the initial identification of two structurally related members, IRF-1 and IRF-2, seven additional members have now been reported [6].
  • In the present study we report the isolation of a cDNA encoding a novel factor, termed IRF-2, that interacts with the same nucleotide sequence elements as IRF-1 [7].
  • IRF-2 has been shown to have oncogenic potential, and our results demonstrate a link between IRF-2 and a gene that is functionally coupled to DNA replication and cell-cycle progression at the G1/S phase transition [8].
  • When the IRF-2 gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice [9].
  • Interferon regulatory factor 2 (IRF-2) sites were altered by significantly associated SNPs in two regions [10].

Biological context of IRF2


Anatomical context of IRF2


Associations of IRF2 with chemical compounds

  • Phosphoaminoacid analysis of HA-tagged IRF2 immunoprecipitated from an asynchronous population of proliferating, metabolically phosphate-labelled cells indicates that this protein is phosphorylated exclusively upon serine residues in vivo [15].
  • With this probe, the constitutive complex C1/C2 corresponds predominantly to IRF2 [16].
  • In C32 cells, an IRF-2 mRNA of 2.4 kb is constitutively expressed in very low amounts but is inducible by Ch-IFN in the absence or presence of cycloheximide [17].

Physical interactions of IRF2

  • Interestingly, full-length IRF-2 in TPA-treated U937 cells occurred as a complex with p300 as well as PCAF and was itself acetylated [13].
  • Yet, Tyr-phosphorylated ICSBP can bind target DNA only through the association with IRF-2 and IRF-1 [18].
  • 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 [19].
  • Interaction of IRF-2 and STAT1 on the promoter depends on the DNA-binding domain of IRF-2 [20].
  • We show here that IRF-2 physically interacts in vitro with NF-kappa B. This interaction may contribute to the repression of the expression of these genes [21].

Enzymatic interactions of IRF2

  • Two-dimensional phosphopeptide mapping of the sites phosphorylated by PKA, PKC, and CKII in vitro demonstrates that these enzymes are capable of phosphorylating IRF2 at multiple distinct sites [15].

Regulatory relationships of IRF2


Other interactions of IRF2


Analytical, diagnostic and therapeutic context of IRF2


  1. Evaluation of the IRF-2 gene as a candidate for PSORS3. Foerster, J., Nolte, I., Schweiger, S., Ehlert, C., Bruinenberg, M., Spaar, K., van der Steege, G., Mulder, M., Kalscheuer, V., Moser, B., Kijas, Z., Seeman, P., Ständer, M., Sterry, W., te Meerman, G. J. Invest. Dermatol. (2004) [Pubmed]
  2. Psoriatic lesional skin exhibits an aberrant expression pattern of interferon regulatory factor-2 (IRF-2). van der Fits, L., van der Wel, L.I., Laman, J.D., Prens, E.P., Verschuren, M.C. J. Pathol. (2003) [Pubmed]
  3. The role of interferon regulatory factor-1 and interferon regulatory factor-2 in IFN-gamma growth inhibition of human breast carcinoma cell lines. Yim, J.H., Ro, S.H., Lowney, J.K., Wu, S.J., Connett, J., Doherty, G.M. J. Interferon Cytokine Res. (2003) [Pubmed]
  4. 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]
  5. Interferon-independent and -induced regulation of Epstein-Barr virus EBNA-1 gene transcription in Burkitt lymphoma. Nonkwelo, C., Ruf, I.K., Sample, J. J. Virol. (1997) [Pubmed]
  6. IRF family of transcription factors as regulators of host defense. Taniguchi, T., Ogasawara, K., Takaoka, A., Tanaka, N. Annu. Rev. Immunol. (2001) [Pubmed]
  7. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Harada, H., Fujita, T., Miyamoto, M., Kimura, Y., Maruyama, M., Furia, A., Miyata, T., Taniguchi, T. Cell (1989) [Pubmed]
  8. Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2. Vaughan, P.S., Aziz, F., van Wijnen, A.J., Wu, S., Harada, H., Taniguchi, T., Soprano, K.J., Stein, J.L., Stein, G.S. Nature (1995) [Pubmed]
  9. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2. Harada, H., Kitagawa, M., Tanaka, N., Yamamoto, H., Harada, K., Ishihara, M., Taniguchi, T. Science (1993) [Pubmed]
  10. LD mapping of maternally and non-maternally derived alleles and atopy in FcepsilonRI-beta. Traherne, J.A., Hill, M.R., Hysi, P., D'Amato, M., Broxholme, J., Mott, R., Moffatt, M.F., Cookson, W.O. Hum. Mol. Genet. (2003) [Pubmed]
  11. 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]
  12. Transcriptional regulation of the 230-kDa bullous pemphigoid antigen gene expression by interferon regulatory factor 1 and interferon regulatory factor 2 in normal human epidermal keratinocytes. Odanagi, M., Kikuchi, Y., Yamazaki, T., Kaneko, T., Nakano, H., Tamai, K., Uitto, J., Vitto, J., Hanada, K. Exp. Dermatol. (2004) [Pubmed]
  13. Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells following phorbol ester treatment. Masumi, A., Ozato, K. J. Biol. Chem. (2001) [Pubmed]
  14. Constitutive activation of Epstein-Barr virus (EBV) nuclear antigen 1 gene transcription by IRF1 and IRF2 during restricted EBV latency. Schaefer, B.C., Paulson, E., Strominger, J.L., Speck, S.H. Mol. Cell. Biol. (1997) [Pubmed]
  15. Phosphorylation of the oncogenic transcription factor interferon regulatory factor 2 (IRF2) in vitro and in vivo. Birnbaum, M.J., van Zundert, B., Vaughan, P.S., Whitmarsh, A.J., van Wijnen, A.J., Davis, R.J., Stein, G.S., Stein, J.L. J. Cell. Biochem. (1997) [Pubmed]
  16. The interferon-stimulable response elements of two human genes detect overlapping sets of transcription factors. Parrington, J., Rogers, N.C., Gewert, D.R., Pine, R., Veals, S.A., Levy, D.E., Stark, G.R., Kerr, I.M. Eur. J. Biochem. (1993) [Pubmed]
  17. Cloning of chicken interferon regulatory factor-2 (IRF-2) cDNA: expression and mapping of the IRF-2 gene. Marienfeld, R., Nanda, I., Zöller, B., Schmid, M., Rebbert, M., Jungwirth, C. J. Interferon Cytokine Res. (1997) [Pubmed]
  18. Phosphorylation events modulate the ability of interferon consensus sequence binding protein to interact with interferon regulatory factors and to bind DNA. Sharf, R., Meraro, D., Azriel, A., Thornton, A.M., Ozato, K., Petricoin, E.F., Larner, A.C., Schaper, F., Hauser, H., Levi, B.Z. J. Biol. Chem. (1997) [Pubmed]
  19. 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]
  20. IFN regulatory factor-2 cooperates with STAT1 to regulate transporter associated with antigen processing-1 promoter activity. Rouyez, M.C., Lestingi, M., Charon, M., Fichelson, S., Buzyn, A., Dusanter-Fourt, I. J. Immunol. (2005) [Pubmed]
  21. Interferon regulatory factor-2 physically interacts with NF-kappa B in vitro and inhibits NF-kappa B induction of major histocompatibility class I and beta 2-microglobulin gene expression in transfected human neuroblastoma cells. Drew, P.D., Franzoso, G., Carlson, L.M., Biddison, W.E., Siebenlist, U., Ozato, K. J. Neuroimmunol. (1995) [Pubmed]
  22. The Role of IRF1 and IRF2 Transcription Factors in Leukaemogenesis. Choo, A., Palladinetti, P., Passioura, T., Shen, S., Lock, R., Symonds, G., Dolnikov, A. Current gene therapy. (2006) [Pubmed]
  23. An IFN regulatory factor-2 DNA-binding domain dominant negative mutant exhibits altered cell growth and gene expression. Rubinstein, Y.R., Driggers, P.H., Ogryzko, V.V., Thornton, A.M., Ozato, K., Pontzer, C.H. Oncogene (2000) [Pubmed]
  24. Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) type IV promoter by interferon regulatory factors 1 and 2. Xi, H., Eason, D.D., Ghosh, D., Dovhey, S., Wright, K.L., Blanck, G. Oncogene (1999) [Pubmed]
  25. Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system. Tanaka, N., Kawakami, T., Taniguchi, T. Mol. Cell. Biol. (1993) [Pubmed]
  26. Nucleolin is involved in interferon regulatory factor-2-dependent transcriptional activation. Masumi, A., Fukazawa, H., Shimazu, T., Yoshida, M., Ozato, K., Komuro, K., Yamaguchi, K. Oncogene (2006) [Pubmed]
  27. Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription. Nelson, N., Marks, M.S., Driggers, P.H., Ozato, K. Mol. Cell. Biol. (1993) [Pubmed]
  28. Molecular characterization of celtix-1, a bromodomain protein interacting with the transcription factor interferon regulatory factor 2. Staal, A., Enserink, J.M., Stein, J.L., Stein, G.S., van Wijnen, A.J. J. Cell. Physiol. (2000) [Pubmed]
  29. Interferon regulatory factor-2 point mutations in human pancreatic tumors. Xi, H., Blanck, G. Int. J. Cancer (2000) [Pubmed]
  30. 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]
  31. IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene expression during phorbol ester-induced promyelocytic HL-60 differentiation. Chung, M.C., Kawamoto, S. J. Biol. Chem. (2004) [Pubmed]
  32. Interferon regulatory factor expression in human breast cancer. Doherty, G.M., Boucher, L., Sorenson, K., Lowney, J. Ann. Surg. (2001) [Pubmed]
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