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Gene Review

IRF4  -  interferon regulatory factor 4

Homo sapiens

Synonyms: IRF-4, Interferon regulatory factor 4, LSIRF, Lymphocyte-specific interferon regulatory factor, MUM1, ...
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Disease relevance of IRF4


High impact information on IRF4

  • Finally, IRF4 and IRF8 together control the termination of pre-B cell receptor signaling and thus promote differentiation to small pre-B cells undergoing light-chain gene rearrangements [6].
  • PU.1 recruits the binding of a second B cell-restricted nuclear factor, NF-EM5, to a DNA site in the immunoglobulin kappa 3' enhancer [7].
  • Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation [7].
  • Expression of wild-type PU.1 increased expression of a reporter construct containing the PU.1 and NF-EM5 binding sites nearly sixfold, whereas the Ser148 mutant form only weakly activated transcription [7].
  • Phosphorylation of bacterially produced PU.1 by purified casein kinase II modified it to a form that interacted with NF-EM5 and that recruited NF-EM5 to bind to DNA [7].

Biological context of IRF4


Anatomical context of IRF4

  • We present evidence that primary murine and human macrophages express IRF4, thereby extending its range of expression to myeloid cells [10].
  • ICSBP expression is restricted to lymphoid and myeloid cells, whereas IRF4 expression has been reported to be lymphoid-restricted [10].
  • Since expression of IRF-4 is mostly confined to lymphoid cells, these data provide a potential mechanism by which IL-4-inducible genes can be regulated in a lineage-specific manner [11].
  • We have isolated a novel cDNA clone encoding interferon (IFN) consensus sequence-binding protein in adult T-cell leukemia cell line or activated T cells (ICSAT); this protein is the human homolog of the recently cloned Pip/LSIRF [12].
  • Surprisingly hLSIRF mRNA was also found in the melanoma line G361 and is expressed in normal melanocytes as well [13].

Associations of IRF4 with chemical compounds


Physical interactions of IRF4


Regulatory relationships of IRF4


Other interactions of IRF4


Analytical, diagnostic and therapeutic context of IRF4

  • Second, MUM1/IRF4 may help in the differential diagnosis of PEL among other lymphomas involving the serous body cavities [3].
  • Furthermore, we find that IRF-4 can interact with signal transducer and activator of transcription (Stat)6 and drive the expression of IL-4-inducible genes [11].
  • In Northern blot analysis, a single transcript of approximately 5 kb was highly expressed in spleen and peripheral blood lymphocyte. hLSIRF mRNA was rapidly induced in peripheral T cells after crosslinking the T-cell receptor [13].
  • To elucidate its role in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which proliferated until higher cellular density than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1 [9].
  • Following purification through immobilized metal affinity, hydrophobic interaction, and gel permeation chromatographies, the renatured protein was shown to be structurally and physically equivalent to a sample of IRF-4 produced in the soluble fraction of E. coli cells [18].


  1. Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma. Iida, S., Rao, P.H., Butler, M., Corradini, P., Boccadoro, M., Klein, B., Chaganti, R.S., Dalla-Favera, R. Nat. Genet. (1997) [Pubmed]
  2. Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA. Sundram, U., Harvell, J.D., Rouse, R.V., Natkunam, Y. Mod. Pathol. (2003) [Pubmed]
  3. Expression of MUM1/IRF4 selectively clusters with primary effusion lymphoma among lymphomatous effusions: implications for disease histogenesis and pathogenesis. Carbone, A., Gloghini, A., Cozzi, M.R., Capello, D., Steffan, A., Monini, P., De Marco, L., Gaidano, G. Br. J. Haematol. (2000) [Pubmed]
  4. Possible involvement of interferon regulatory factor 4 (IRF4) in a clinical subtype of adult T-cell leukemia. Imaizumi, Y., Kohno, T., Yamada, Y., Ikeda, S., Tanaka, Y., Tomonaga, M., Matsuyama, T. Jpn. J. Cancer Res. (2001) [Pubmed]
  5. Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy. Schmidt, M., Hochhaus, A., König-Merediz, S.A., Brendel, C., Proba, J., Hoppe, G.J., Wittig, B., Ehninger, G., Hehlmann, R., Neubauer, A. J. Clin. Oncol. (2000) [Pubmed]
  6. Transcriptional control of early B cell development. Busslinger, M. Annu. Rev. Immunol. (2004) [Pubmed]
  7. Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Pongubala, J.M., Van Beveren, C., Nagulapalli, S., Klemsz, M.J., McKercher, S.R., Maki, R.A., Atchison, M.L. Science (1993) [Pubmed]
  8. Differential expression of IFN regulatory factor 4 gene in human monocyte-derived dendritic cells and macrophages. Lehtonen, A., Veckman, V., Nikula, T., Lahesmaa, R., Kinnunen, L., Matikainen, S., Julkunen, I. J. Immunol. (2005) [Pubmed]
  9. Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-gamma (MIG) gene expression in B-cell malignancy. Uranishi, M., Iida, S., Sanda, T., Ishida, T., Tajima, E., Ito, M., Komatsu, H., Inagaki, H., Ueda, R. Leukemia (2005) [Pubmed]
  10. Differential expression and distinct functions of IFN regulatory factor 4 and IFN consensus sequence binding protein in macrophages. Marecki, S., Atchison, M.L., Fenton, M.J. J. Immunol. (1999) [Pubmed]
  11. Lineage-specific modulation of interleukin 4 signaling by interferon regulatory factor 4. Gupta, S., Jiang, M., Anthony, A., Pernis, A.B. J. Exp. Med. (1999) [Pubmed]
  12. A novel interferon regulatory factor family transcription factor, ICSAT/Pip/LSIRF, that negatively regulates the activity of interferon-regulated genes. Yamagata, T., Nishida, J., Tanaka, S., Sakai, R., Mitani, K., Yoshida, M., Taniguchi, T., Yazaki, Y., Hirai, H. Mol. Cell. Biol. (1996) [Pubmed]
  13. Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25. Grossman, A., Mittrücker, H.W., Nicholl, J., Suzuki, A., Chung, S., Antonio, L., Suggs, S., Sutherland, G.R., Siderovski, D.P., Mak, T.W. Genomics (1996) [Pubmed]
  14. Activation and regulation of interferon regulatory factor 4 in HTLV type 1-infected T lymphocytes. Sharma, S., Mamane, Y., Grandvaux, N., Bartlett, J., Petropoulos, L., Lin, R., Hiscott, J. AIDS Res. Hum. Retroviruses (2000) [Pubmed]
  15. IRF-4 expression in the human myeloid lineage: up-regulation during dendritic cell differentiation and inhibition by 1alpha,25-dihydroxyvitamin D3. Gauzzi, M.C., Purificato, C., Conti, L., Adorini, L., Belardelli, F., Gessani, S. J. Leukoc. Biol. (2005) [Pubmed]
  16. Down-regulation of interferon regulatory factor 4 gene expression in leukemic cells due to hypermethylation of CpG motifs in the promoter region. Ortmann, C.A., Burchert, A., Hölzle, K., Nitsche, A., Wittig, B., Neubauer, A., Schmidt, M. Nucleic Acids Res. (2005) [Pubmed]
  17. Stage-specific modulation of IFN-regulatory factor 4 function by Krüppel-type zinc finger proteins. Gupta, S., Anthony, A., Pernis, A.B. J. Immunol. (2001) [Pubmed]
  18. Folding and purification of a recombinantly expressed interferon regulatory factor, IRF-4. Moellering, B.J., Yoshinaga, S.K., Hui, A., Delaney, J.M., Hara, S., Narhi, L.O., Westcott, K.R. Protein Expr. Purif. (1999) [Pubmed]
  19. Active repression of IFN regulatory factor-1-mediated transactivation by IFN regulatory factor-4. Yoshida, K., Yamamoto, K., Kohno, T., Hironaka, N., Yasui, K., Kojima, C., Mukae, H., Kadota, J., Suzuki, S., Honma, K., Kohno, S., Matsuyama, T. Int. Immunol. (2005) [Pubmed]
  20. Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation. Sciammas, R., Shaffer, A.L., Schatz, J.H., Zhao, H., Staudt, L.M., Singh, H. Immunity (2006) [Pubmed]
  21. Pathobiology of primary mediastinal B-cell lymphoma. Pileri, S.A., Zinzani, P.L., Gaidano, G., Falini, B., Gaulard, P., Zucca, E., Sabattini, E., Ascani, S., Rossi, M., Cavalli, F. Leuk. Lymphoma (2003) [Pubmed]
  22. Interphase detection of t(4;14)(p16.3;q32.3) by in situ hybridization and FGFR3 overexpression in plasma cell malignancies. Nakazawa, N., Nishida, K., Tamura, A., Kobayashi, M., Iwai, T., Horiike, S., Nishigaki, H., Otsuki, T., Tomiyama, Y., Fujii, H., Kashima, K., Taniwaki, M. Cancer Genet. Cytogenet. (2000) [Pubmed]
  23. Interphase detection of immunoglobulin heavy chain gene translocations with specific oncogene loci in 173 patients with B-cell lymphoma. Tamura, A., Miura, I., Iida, S., Yokota, S., Horiike, S., Nishida, K., Fujii, H., Nakamura, S., Seto, M., Ueda, R., Taniwaki, M. Cancer Genet. Cytogenet. (2001) [Pubmed]
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