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Gene Review

IRF5  -  interferon regulatory factor 5

Homo sapiens

Synonyms: IRF-5, Interferon regulatory factor 5
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Disease relevance of IRF5


High impact information on IRF5

  • It also shows that the range of IRF-5 immunoregulatory target genes includes members of the cytokine and chemokine superfamilies [1].
  • Mutation of these residues from serine to alanine dramatically decreased phosphorylation and resulted in a substantial loss of IRF-5 transactivation in infected cells [1].
  • Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes [1].
  • By transient- transfection assay, we identified constitutive-activation (amino acids [aa] 410 to 489) and autoinhibitory (aa 490 to 539) domains in the IRF-5 polypeptide [1].
  • The combination IFN-beta and irinotecan (CPT-11) cooperatively inhibits cell growth and IRF-5 synergizes with it to further promote apoptosis [4].

Biological context of IRF5


Anatomical context of IRF5

  • In human primary plasmacytoid dendritic cells (PDC), IRF-5 is transcribed into four distinct alternatively spliced isoforms (V1, V2, V3, and V4), whereas in human primary peripheral blood mononuclear cells two additional new isoforms (V5 and V6) were identified [10].

Associations of IRF5 with chemical compounds

  • The formation of the IRF-5/IRF-7 heterodimer is dependent on IRF-7 phosphorylation, as shown by the glutathione S-transferase pull-down and immunoprecipitation assays [11].
  • Mutation of two leucine residues in the NES motif to alanine, or three adjacent Ser/Thr residues to the phosphomimetic Asp, results in constitutively nuclear IRF-5 and suggests that phosphorylation of adjacent Ser/Thr residues may contribute to IRF-5 nuclear accumulation in virus-induced cells [12].
  • Expression of IRF-5 was induced in p53+/+ cells (MCF7 and NHDF), but not inp53-/- cells (H1299) when DNA was damaged by gamma-irradiation, UV-radiation, or adriamycin treatment in a wild-type p53-dependent manner [13].

Regulatory relationships of IRF5


Other interactions of IRF5


Analytical, diagnostic and therapeutic context of IRF5


  1. Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes. Barnes, B.J., Kellum, M.J., Field, A.E., Pitha, P.M. Mol. Cell. Biol. (2002) [Pubmed]
  2. Statistical false positive or true disease pathway? Todd, J.A. Nat. Genet. (2006) [Pubmed]
  3. Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death. Barnes, B.J., Kellum, M.J., Pinder, K.E., Frisancho, J.A., Pitha, P.M. Cancer Res. (2003) [Pubmed]
  4. Signaling through IFN regulatory factor-5 sensitizes p53-deficient tumors to DNA damage-induced apoptosis and cell death. Hu, G., Mancl, M.E., Barnes, B.J. Cancer Res. (2005) [Pubmed]
  5. Interferon regulatory factor-5-regulated pathways as a target for colorectal cancer therapeutics. Hu, G., Barnes, B.J. Expert review of anticancer therapy. (2006) [Pubmed]
  6. The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren's syndrome. Miceli-Richard, C., Gestermann, N., Ittah, M., Comets, E., Loiseau, P., Puechal, X., Hachulla, E., Gottenberg, J.E., Lebon, P., Becquemont, L., Mariette, X. Arthritis Rheum. (2009) [Pubmed]
  7. Association between the IRF5 rs2004640 functional polymorphism and systemic sclerosis: a new perspective for pulmonary fibrosis. Dieudé, P., Guedj, M., Wipff, J., Avouac, J., Fajardy, I., Diot, E., Granel, B., Sibilia, J., Cabane, J., Mouthon, L., Cracowski, J.L., Carpentier, P.H., Hachulla, E., Meyer, O., Kahan, A., Boileau, C., Allanore, Y. Arthritis Rheum. (2009) [Pubmed]
  8. Interferon regulatory factor 5 represses expression of the Epstein-Barr virus oncoprotein LMP1: braking of the IRF7/LMP1 regulatory circuit. Ning, S., Huye, L.E., Pagano, J.S. J. Virol. (2005) [Pubmed]
  9. Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis. Rueda, B., Reddy, M.V., Gonz??lez-Gay, M.A., Balsa, A., Pascual-Salcedo, D., Petersson, I.F., Eimon, A., Paira, S., Scherbarth, H.R., Pons-Estel, B.A., Gonz??lez-Escribano, M.F., Alarc??n-Riquelme, M.E., Mart??n, J. Arthritis Rheum. (2006) [Pubmed]
  10. Two discrete promoters regulate the alternatively spliced human interferon regulatory factor-5 isoforms. Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function. Mancl, M.E., Hu, G., Sangster-Guity, N., Olshalsky, S.L., Hoops, K., Fitzgerald-Bocarsly, P., Pitha, P.M., Pinder, K., Barnes, B.J. J. Biol. Chem. (2005) [Pubmed]
  11. Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes. Barnes, B.J., Field, A.E., Pitha-Rowe, P.M. J. Biol. Chem. (2003) [Pubmed]
  12. A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization. Lin, R., Yang, L., Arguello, M., Penafuerte, C., Hiscott, J. J. Biol. Chem. (2005) [Pubmed]
  13. Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53. Mori, T., Anazawa, Y., Iiizumi, M., Fukuda, S., Nakamura, Y., Arakawa, H. Oncogene (2002) [Pubmed]
  14. 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]
  15. The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. Schoenemeyer, A., Barnes, B.J., Mancl, M.E., Latz, E., Goutagny, N., Pitha, P.M., Fitzgerald, K.A., Golenbock, D.T. J. Biol. Chem. (2005) [Pubmed]
  16. The Kaposi's Sarcoma-associated Herpesvirus-encoded vIRF-3 Inhibits Cellular IRF-5. Wies, E., Hahn, A.S., Schmidt, K., Viebahn, C., Rohland, N., Lux, A., Schellhorn, T., Holzer, A., Jung, J.U., Neipel, F. J. Biol. Chem. (2009) [Pubmed]
  17. Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection. Barnes, B.J., Richards, J., Mancl, M., Hanash, S., Beretta, L., Pitha, P.M. J. Biol. Chem. (2004) [Pubmed]
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