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Regulation of immunity and oncogenesis by the IRF transcription factor family

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Abstract

Nine interferon regulatory factors (IRFs) compose a family of transcription factors in mammals. Although this family was originally identified in the context of the type I interferon system, subsequent studies have revealed much broader functions performed by IRF members in host defense. In this review, we provide an update on the current knowledge of their roles in immune responses, immune cell development, and regulation of oncogenesis.

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References

  1. Mamane Y, Heylbroeck C, Genin P, Algarte M, Servant MJ, LePage C, DeLuca C, Kwon H, Lin R, Hiscott J (1999) Interferon regulatory factors: the next generation. Gene 237:1–14

    Article  PubMed  CAS  Google Scholar 

  2. Taniguchi T, Ogasawara K, Takaoka A, Tanaka N (2001) IRF family of transcription factors as regulators of host defense. Annu Rev Immunol 19:623–655

    Article  PubMed  CAS  Google Scholar 

  3. Fujii Y, Shimizu T, Kusumoto M, Kyogoku Y, Taniguchi T, Hakoshima T (1999) Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences. EMBO J 18:5028–5041

    Article  PubMed  CAS  Google Scholar 

  4. Meraro D, Hashmueli S, Koren B, Azriel A, Oumard A, Kirchhoff S, Hauser H, Nagulapalli S, Atchison ML, Levi BZ (1999) Protein-protein and DNA-protein interactions affect the activity of lymphoid-specific IFN regulatory factors. J Immunol 163:6468–6478

    PubMed  CAS  Google Scholar 

  5. Wathelet MG, Lin CH, Parekh BS, Ronco LV, Howley PM, Maniatis T (1998) Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell 1:507–518

    Article  PubMed  CAS  Google Scholar 

  6. Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6:644–658

    Article  PubMed  CAS  Google Scholar 

  7. Honda K, Takaoka A, Taniguchi T (2006) Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity 25:349–360

    Article  PubMed  CAS  Google Scholar 

  8. Ozato K, Tailor P, Kubota T (2007) The interferon regulatory factor family in host defense: mechanism of action. J Biol Chem 282:20065–20069

    Article  PubMed  CAS  Google Scholar 

  9. Tamura T, Yanai H, Savitsky D, Taniguchi T (2008) The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26:535–584

    Article  PubMed  CAS  Google Scholar 

  10. Takaoka A, Tamura T, Taniguchi T (2008) Interferon regulatory factor family of transcription factors and regulation of oncogenesis. Cancer Sci 99:467–478

    Article  PubMed  CAS  Google Scholar 

  11. Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216

    Article  PubMed  CAS  Google Scholar 

  12. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  PubMed  CAS  Google Scholar 

  13. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE (2004) The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci USA 101:17264–17269

    Article  PubMed  CAS  Google Scholar 

  14. Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O, Akira S (2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23:19–28

    Article  PubMed  CAS  Google Scholar 

  15. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii K, Yamaguchi O, Otsu K, Tsujimura T, Koh C, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105

    Article  PubMed  CAS  Google Scholar 

  16. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M Jr, Akira S, Yonehara S, Kato A, Fujita T (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175:2851–2858

    PubMed  CAS  Google Scholar 

  17. Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4:491–496

    Article  PubMed  CAS  Google Scholar 

  18. Sharma S, tenOever BR, Grandvaux N, Zhou GP, Lin R, Hiscott J (2003) Triggering the interferon antiviral response through an IKK-related pathway. Science 300:1148–1151

    Article  PubMed  CAS  Google Scholar 

  19. Mori M, Yoneyama M, Ito T, Takahashi K, Inagaki F, Fujita T (2004) Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation. J Biol Chem 279:9698–9702

    Article  PubMed  CAS  Google Scholar 

  20. Panne D, McWhirter SM, Maniatis T, Harrison SC (2007) Interferon response factor 3 is regulated by a dual phosphorylation dependent switch. J Biol Chem 282(31):22816–22822

    Google Scholar 

  21. Yanai H, Chen HM, Inuzuka T, Kondo S, Mak TW, Takaoka A, Honda K, Taniguchi T (2007) Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. Proc Natl Acad Sci USA 104:3402–3407

    Article  PubMed  CAS  Google Scholar 

  22. Paun A, Reinert JT, Jiang Z, Medin C, Balkhi MY, Fitzgerald KA, Pitha PM (2008) Functional characterization of murine interferon regulatory factor 5 (IRF-5) and its role in the innate antiviral response. J Biol Chem 283:14295–14308

    Article  PubMed  CAS  Google Scholar 

  23. Barnes BJ, Field AE, Pitha-Rowe PM (2003) Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes. J Biol Chem 278:16630–16641

    Article  PubMed  CAS  Google Scholar 

  24. Lin R, Yang L, Arguello M, Penafuerte C, Hiscott J (2005) A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization. J Biol Chem 280:3088–3095

    Article  PubMed  CAS  Google Scholar 

  25. Tailor P, Tamura T, Kong HJ, Kubota T, Kubota M, Borghi P, Gabriele L, Ozato K (2007) Type I interferon induction in dendritic cells requires IRF-8 that effects the feedback phase of transcription. Immunity 27(2):228–239

    Google Scholar 

  26. Stetson DB, Medzhitov R (2006) Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity 24:93–103

    Article  PubMed  CAS  Google Scholar 

  27. Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H, Sato S, Yamamoto M, Uematsu S, Kawai T, Takeuchi O, Akira S (2006) A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat Immunol 7:40–48

    Article  PubMed  CAS  Google Scholar 

  28. Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T (2007) DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 448:501–505

    Article  PubMed  CAS  Google Scholar 

  29. Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T (2008) Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules. Proc Natl Acad Sci USA 105:5477–5482

    Article  PubMed  Google Scholar 

  30. Stetson DB, Ko JS, Heidmann T, Medzhitov R (2008) Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134:587–598

    Article  PubMed  CAS  Google Scholar 

  31. Ishikawa H, Barber GN (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455:674–678

    Article  PubMed  CAS  Google Scholar 

  32. Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, Lei C, He X, Zhang L, Tien P, Shu HB (2008) The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 29:538–550

    Article  PubMed  CAS  Google Scholar 

  33. Kawai T, Akira S (2006) TLR signaling. Cell Death Differ 13:816–825

    Article  PubMed  CAS  Google Scholar 

  34. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145

    Article  PubMed  CAS  Google Scholar 

  35. Kawai T, Takeuchi O, Fujita T, Inoue J, Muhlradt PF, Sato S, Hoshino K, Akira S (2001) Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol 167:5887–5894

    PubMed  CAS  Google Scholar 

  36. Sakaguchi S, Negishi H, Asagiri M, Nakajima C, Mizutani T, Takaoka A, Honda K, Taniguchi T (2003) Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock. Biochem Biophys Res Commun 306:860–866

    Article  PubMed  CAS  Google Scholar 

  37. Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T (2005) IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434:772–777

    Article  PubMed  CAS  Google Scholar 

  38. Werner SL, Barken D, Hoffmann A (2005) Stimulus specificity of gene expression programs determined by temporal control of IKK activity. Science 309:1857–1861

    Article  PubMed  CAS  Google Scholar 

  39. Flandin JF, Chano F, Descoteaux A (2006) RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon-gamma-primed macrophages. Eur J Immunol 36:411–420

    Article  PubMed  CAS  Google Scholar 

  40. Negishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S, Koshiba R, Yanai H, Seko Y, Shitara H, Bishop K, Yonekawa H, Tamura T, Kaisho T, Taya C, Taniguchi T, Honda K (2008) A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. Proc Natl Acad Sci USA 105:20446–20451

    Article  PubMed  Google Scholar 

  41. Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci USA 101:3516–3521

    Article  PubMed  CAS  Google Scholar 

  42. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V, Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von Bernuth H, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, Lebon P, Heron B, Vallee L, Quintana-Murci L, Hovnanian A, Rozenberg F, Vivier E, Geissmann F, Tardieu M, Abel L, Casanova JL (2007) TLR3 deficiency in patients with herpes simplex encephalitis. Science 317:1522–1527

    Article  PubMed  CAS  Google Scholar 

  43. Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sovath S, Han J, Beutler B (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424:743–748

    Article  PubMed  CAS  Google Scholar 

  44. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301:640–643

    Article  PubMed  CAS  Google Scholar 

  45. Honda K, Yanai H, Mizutani T, Negishi H, Shimada N, Suzuki N, Ohba Y, Takaoka A, Yeh WC, Taniguchi T (2004) Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci USA 101:15416–15421

    Article  PubMed  CAS  Google Scholar 

  46. Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O, Akira S (2004) Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol 5:1061–1068

    Article  PubMed  CAS  Google Scholar 

  47. Hoshino K, Sugiyama T, Matsumoto M, Tanaka T, Saito M, Hemmi H, Ohara O, Akira S, Kaisho T (2006) IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9. Nature 440:949–953

    Article  PubMed  CAS  Google Scholar 

  48. Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, Kano S, Honda K, Ohba Y, Mak TW, Taniguchi T (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434:243–249

    Article  PubMed  CAS  Google Scholar 

  49. Yasuda K, Richez C, Maciaszek JW, Agrawal N, Akira S, Marshak-Rothstein A, Rifkin IR (2007) Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for IL-6 production. J Immunol 178:6876–6885

    PubMed  CAS  Google Scholar 

  50. Balkhi MY, Fitzgerald KA, Pitha PM (2008) Functional regulation of MyD88-activated interferon regulatory factor 5 by K63-linked polyubiquitination. Mol Cell Biol 28:7296–7308

    Article  PubMed  CAS  Google Scholar 

  51. Chen W, Lam SS, Srinath H, Jiang Z, Correia JJ, Schiffer CA, Fitzgerald KA, Lin K, Royer WE Jr (2008) Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5. Nat Struct Mol Biol 15:1213–1220

    Article  PubMed  CAS  Google Scholar 

  52. Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, Gonzalez Escribano MF, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martin J, Altshuler D, Behrens TW, Alarcon-Riquelme ME (2006) A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 38:550–555

    Article  PubMed  CAS  Google Scholar 

  53. Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K (2006) Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. Proc Natl Acad Sci USA 103:15136–15141

    Article  PubMed  CAS  Google Scholar 

  54. Yarilina A, Park-Min KH, Antoniv T, Hu X, Ivashkiv LB (2008) TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes. Nat Immunol 9:378–387

    Article  PubMed  CAS  Google Scholar 

  55. Negishi H, Ohba Y, Yanai H, Takaoka A, Honma K, Yui K, Matsuyama T, Taniguchi T, Honda K (2005) Negative regulation of Toll-like-receptor signaling by IRF-4. Proc Natl Acad Sci USA 102:15989–15994

    Article  PubMed  CAS  Google Scholar 

  56. Honma K, Udono H, Kohno T, Yamamoto K, Ogawa A, Takemori T, Kumatori A, Suzuki S, Matsuyama T, Yui K (2005) Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS. Proc Natl Acad Sci USA 102:16001–16006

    Article  PubMed  CAS  Google Scholar 

  57. Ma S, Pathak S, Trinh L, Lu R (2008) Interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to down-regulate pre-B-cell receptor and promote cell-cycle withdrawal in pre-B-cell development. Blood 111:1396–1403

    Article  PubMed  CAS  Google Scholar 

  58. Mudter J, Amoussina L, Schenk M, Yu J, Brustle A, Weigmann B, Atreya R, Wirtz S, Becker C, Hoffman A, Atreya I, Biesterfeld S, Galle PR, Lehr HA, Rose-John S, Mueller C, Lohoff M, Neurath MF (2008) The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6. J Clin Invest 118:2415–2426

    PubMed  CAS  Google Scholar 

  59. Zhao J, Kong HJ, Li H, Huang B, Yang M, Zhu C, Bogunovic M, Zheng F, Mayer L, Ozato K, Unkeless J, Xiong H (2006) IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways. J Biol Chem 281:10073–10080

    Article  PubMed  CAS  Google Scholar 

  60. Tsujimura H, Tamura T, Kong HJ, Nishiyama A, Ishii KJ, Klinman DM, Ozato K (2004) Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells. J Immunol 172:6820–6827

    PubMed  CAS  Google Scholar 

  61. Masumi A, Tamaoki S, Wang IM, Ozato K, Komuro K (2002) IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages. FEBS Lett 531:348–353

    Article  PubMed  CAS  Google Scholar 

  62. Schiavoni G, Mattei F, Sestili P, Borghi P, Venditti M, Morse HC III, Belardelli F, Gabriele L (2002) ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. J Exp Med 196:1415–1425

    Article  PubMed  CAS  Google Scholar 

  63. Zhu C, Rao K, Xiong H, Gagnidze K, Li F, Horvath C, Plevy S (2003) Activation of the murine interleukin-12 p40 promoter by functional interactions between NFAT and ICSBP. J Biol Chem 278:39372–39382

    Article  PubMed  CAS  Google Scholar 

  64. Bailey CM, Hendrix MJ (2008) IRF6 in development and disease: a mediator of quiescence and differentiation. Cell Cycle 7:1925–1930

    PubMed  CAS  Google Scholar 

  65. DiPerna G, Stack J, Bowie AG, Boyd A, Kotwal G, Zhang Z, Arvikar S, Latz E, Fitzgerald KA, Marshall WL (2004) Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors. J Biol Chem 279:36570–36578

    Article  PubMed  CAS  Google Scholar 

  66. Schroder M, Baran M, Bowie AG (2008) Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKepsilon-mediated IRF activation. EMBO J 27:2147–2157

    Article  PubMed  CAS  Google Scholar 

  67. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, Ray SC, Gale M Jr, Lemon SM (2005) Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA 102:2992–2997

    Article  PubMed  CAS  Google Scholar 

  68. Seth RB, Sun L, Chen ZJ (2006) Antiviral innate immunity pathways. Cell Res 16:141–147

    Article  PubMed  CAS  Google Scholar 

  69. Barro M, Patton JT (2007) Rotavirus NSP1 inhibits expression of type I interferon by antagonizing the function of interferon regulatory factors IRF3, IRF5, and IRF7. J Virol 81:4473–4481

    Article  PubMed  CAS  Google Scholar 

  70. Graff JW, Mitzel DN, Weisend CM, Flenniken ML, Hardy ME (2002) Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1. J Virol 76:9545–9550

    Article  PubMed  CAS  Google Scholar 

  71. Yu Y, Wang SE, Hayward GS (2005) The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22:59–70

    Article  PubMed  CAS  Google Scholar 

  72. Offermann MK (2007) Kaposi sarcoma herpesvirus-encoded interferon regulator factors. Curr Top Microbiol Immunol 312:185–209

    Article  PubMed  CAS  Google Scholar 

  73. Paun A, Pitha PM (2007) The IRF family, revisited. Biochimie 89:744–753

    Article  PubMed  CAS  Google Scholar 

  74. Burysek L, Yeow WS, Lubyova B, Kellum M, Schafer SL, Huang YQ, Pitha PM (1999) Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300. J Virol 73:7334–7342

    PubMed  CAS  Google Scholar 

  75. Li M, Damania B, Alvarez X, Ogryzko V, Ozato K, Jung JU (2000) Inhibition of p300 histone acetyltransferase by viral interferon regulatory factor. Mol Cell Biol 20:8254–8263

    Article  PubMed  CAS  Google Scholar 

  76. Lin R, Genin P, Mamane Y, Sgarbanti M, Battistini A, Harrington WJ Jr, Barber GN, Hiscott J (2001) HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene 20:800–811

    Article  PubMed  CAS  Google Scholar 

  77. Burysek L, Yeow WS, Pitha PM (1999) Unique properties of a second human herpesvirus 8-encoded interferon regulatory factor (vIRF-2). J Hum Virol 2:19–32

    PubMed  CAS  Google Scholar 

  78. Joo CH, Shin YC, Gack M, Wu L, Levy D, Jung JU (2007) Inhibition of interferon regulatory factor 7 (IRF7)-mediated interferon signal transduction by the Kaposi’s sarcoma-associated herpesvirus viral IRF homolog vIRF3. J Virol 81:8282–8292

    Article  PubMed  CAS  Google Scholar 

  79. Wies E, Hahn AS, Schmidt K, Viebahn C, Rohland N, Lux A, Schellhorn T, Holzer A, Jung JU, Neipel F (2009) The Kaposi’s sarcoma-associated herpesvirus encoded vIRF-3 inhibits cellular IRF-5. J Biol Chem (in press)

  80. Pagano JS (1999) Epstein-Barr virus: the first human tumor virus and its role in cancer. Proc Assoc Am Physicians 111:573–580

    Article  PubMed  CAS  Google Scholar 

  81. Ning S, Campos AD, Darnay BG, Bentz GL, Pagano JS (2008) TRAF6 and the three C-terminal lysine sites on IRF7 are required for its ubiquitination-mediated activation by the tumor necrosis factor receptor family member latent membrane protein 1. Mol Cell Biol 28:6536–6546

    Article  PubMed  CAS  Google Scholar 

  82. Song YJ, Izumi KM, Shinners NP, Gewurz BE, Kieff E (2008) IRF7 activation by Epstein-Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3. Proc Natl Acad Sci USA 105:18448–18453

    Article  PubMed  Google Scholar 

  83. Zhang L, Zhang J, Lambert Q, Der CJ, Del Valle L, Miklossy J, Khalili K, Zhou Y, Pagano JS (2004) Interferon regulatory factor 7 is associated with Epstein-Barr virus-transformed central nervous system lymphoma and has oncogenic properties. J Virol 78:12987–12995

    Article  PubMed  CAS  Google Scholar 

  84. zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350

    Article  PubMed  CAS  Google Scholar 

  85. Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ (2000) Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem 275:6764–6769

    Article  PubMed  CAS  Google Scholar 

  86. Ronco LV, Karpova AY, Vidal M, Howley PM (1998) Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev 12:2061–2072

    Article  PubMed  CAS  Google Scholar 

  87. Suzuki S, Honma K, Matsuyama T, Suzuki K, Toriyama K, Akitoyo I, Yamamoto K, Suematsu T, Nakamura M, Yui K, Kumatori A (2004) Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha- dendritic cell development. Proc Natl Acad Sci USA 101:8981–8986

    Article  PubMed  CAS  Google Scholar 

  88. Tamura T, Tailor P, Yamaoka K, Kong HJ, Tsujimura H, O’Shea JJ, Singh H, Ozato K (2005) IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J Immunol 174:2573–2581

    PubMed  CAS  Google Scholar 

  89. Tsujimura H, Tamura T, Ozato K (2003) Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells. J Immunol 170:1131–1135

    PubMed  CAS  Google Scholar 

  90. Aliberti J, Schulz O, Pennington DJ, Tsujimura H, Reis e Sousa C, Ozato K, Sher A (2003) Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells. Blood 101:305–310

    Article  PubMed  CAS  Google Scholar 

  91. Esashi E, Wang YH, Perng O, Qin XF, Liu YJ, Watowich SS (2008) The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity 28:509–520

    Article  PubMed  CAS  Google Scholar 

  92. Tailor P, Tamura T, Morse HC III, Ozato K (2008) The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood 111:1942–1945

    Article  PubMed  CAS  Google Scholar 

  93. Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, Holmberg D, Zweier C, den Hollander NS, Kant SG, Holter W, Rauch A, Zhuang Y, Reizis B (2008) Transcription factor E2–2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135:37–48

    Article  PubMed  CAS  Google Scholar 

  94. Schiavoni G, Mattei F, Borghi P, Sestili P, Venditti M, Morse HC III, Belardelli F, Gabriele L (2004) ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood 103:2221–2228

    Article  PubMed  CAS  Google Scholar 

  95. Gabriele L, Fragale A, Borghi P, Sestili P, Stellacci E, Venditti M, Schiavoni G, Sanchez M, Belardelli F, Battistini A (2006) IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features. J Leukoc Biol 80:1500–1511

    Article  PubMed  CAS  Google Scholar 

  96. Honda K, Mizutani T, Taniguchi T (2004) Negative regulation of IFN-alpha/beta signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells. Proc Natl Acad Sci USA 101:2416–2421

    Article  PubMed  CAS  Google Scholar 

  97. Ichikawa E, Hida S, Omatsu Y, Shimoyama S, Takahara K, Miyagawa S, Inaba K, Taki S (2004) Defective development of splenic and epidermal CD4 + dendritic cells in mice deficient for IFN regulatory factor-2. Proc Natl Acad Sci USA 101:3909–3914

    Article  PubMed  CAS  Google Scholar 

  98. Holtschke T, Lohler J, Kanno Y, Fehr T, Giese N, Rosenbauer F, Lou J, Knobeloch KP, Gabriele L, Waring JF, Bachmann MF, Zinkernagel RM, Morse HC III, Ozato K, Horak I (1996) Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell 87:307–317

    Article  PubMed  CAS  Google Scholar 

  99. Scheller M, Foerster J, Heyworth CM, Waring JF, Lohler J, Gilmore GL, Shadduck RK, Dexter TM, Horak I (1999) Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein. Blood 94:3764–3771

    PubMed  CAS  Google Scholar 

  100. Tamura T, Nagamura-Inoue T, Shmeltzer Z, Kuwata T, Ozato K (2000) ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages. Immunity 13:155–165

    Article  PubMed  CAS  Google Scholar 

  101. Tsujimura H, Nagamura-Inoue T, Tamura T, Ozato K (2002) IFN consensus sequence binding protein/IFN regulatory factor-8 guides bone marrow progenitor cells toward the macrophage lineage. J Immunol 169:1261–1269

    PubMed  CAS  Google Scholar 

  102. Qian Z, Fernald AA, Godley LA, Larson RA, Le Beau MM (2002) Expression profiling of CD34 + hematopoietic stem/progenitor cells reveals distinct subtypes of therapy-related acute myeloid leukemia. Proc Natl Acad Sci USA 99:14925–14930

    Article  PubMed  CAS  Google Scholar 

  103. Gabriele L, Phung J, Fukumoto J, Segal D, Wang IM, Giannakakou P, Giese NA, Ozato K, Morse HC III (1999) Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein. J Exp Med 190:411–421

    Article  PubMed  CAS  Google Scholar 

  104. Schmidt M, Nagel S, Proba J, Thiede C, Ritter M, Waring JF, Rosenbauer F, Huhn D, Wittig B, Horak I, Neubauer A (1998) Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias. Blood 91:22–29

    PubMed  CAS  Google Scholar 

  105. Schmidt M, Hochhaus A, Nitsche A, Hehlmann R, Neubauer A (2001) Expression of nuclear transcription factor interferon consensus sequence binding protein in chronic myeloid leukemia correlates with pretreatment risk features and cytogenetic response to interferon-alpha. Blood 97:3648–3650

    Article  PubMed  CAS  Google Scholar 

  106. Diaz-Blanco E, Bruns I, Neumann F, Fischer JC, Graef T, Rosskopf M, Brors B, Pechtel S, Bork S, Koch A, Baer A, Rohr UP, Kobbe G, Haeseler A, Gattermann N, Haas R, Kronenwett R (2007) Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phase. Leukemia 21:494–504

    Article  PubMed  CAS  Google Scholar 

  107. Tamura T, Kong HJ, Tunyaplin C, Tsujimura H, Calame K, Ozato K (2003) ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells. Blood 102:4547–4554

    Article  PubMed  CAS  Google Scholar 

  108. Burchert A, Cai D, Hofbauer LC, Samuelsson MK, Slater EP, Duyster J, Ritter M, Hochhaus A, Muller R, Eilers M, Schmidt M, Neubauer A (2004) Interferon consensus sequence binding protein (ICSBP; IRF-8) antagonizes BCR/ABL and down-regulates bcl-2. Blood 103:3480–3489

    Article  PubMed  CAS  Google Scholar 

  109. Schmidt M, Bies J, Tamura T, Ozato K, Wolff L (2004) The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up-regulates expression of tumor suppressor p15(Ink4b) in murine myeloid cells. Blood 103:4142–4149

    Article  PubMed  CAS  Google Scholar 

  110. Huang W, Saberwal G, Horvath E, Zhu C, Lindsey S, Eklund EA (2006) Leukemia-associated, constitutively active mutants of SHP2 protein tyrosine phosphatase inhibit NF1 transcriptional activation by the interferon consensus sequence binding protein. Mol Cell Biol 26:6311–6332

    Article  PubMed  CAS  Google Scholar 

  111. Zhu C, Saberwal G, Lu Y, Platanias LC, Eklund EA (2004) The interferon consensus sequence-binding protein activates transcription of the gene encoding neurofibromin 1. J Biol Chem 279:50874–50885

    Article  PubMed  CAS  Google Scholar 

  112. Dror N, Rave-Harel N, Burchert A, Azriel A, Tamura T, Tailor P, Neubauer A, Ozato K, Levi BZ (2007) Interferon regulatory factor-8 is indispensable for the expression of promyelocytic leukemia and the formation of nuclear bodies in myeloid cells. J Biol Chem 282:5633–5640

    Article  PubMed  CAS  Google Scholar 

  113. Tamura T, Thotakura P, Tanaka TS, Ko MS, Ozato K (2005) Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Blood 106:1938–1947

    Article  PubMed  CAS  Google Scholar 

  114. Rosenbauer F, Kallies A, Scheller M, Knobeloch KP, Rock CO, Schwieger M, Stocking C, Horak I (2002) Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion. EMBO J 21:211–220

    Article  PubMed  CAS  Google Scholar 

  115. Eisenbeis CF, Singh H, Storb U (1995) Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator. Genes Dev 9:1377–1387

    Article  PubMed  CAS  Google Scholar 

  116. Meraro D, Gleit-Kielmanowicz M, Hauser H, Levi BZ (2002) IFN-stimulated gene 15 is synergistically activated through interactions between the myelocyte/lymphocyte-specific transcription factors, PU.1, IFN regulatory factor-8/IFN consensus sequence binding protein, and IFN regulatory factor-4: characterization of a new subtype of IFN-stimulated response element. J Immunol 168:6224–6231

    PubMed  CAS  Google Scholar 

  117. Laricchia-Robbio L, Tamura T, Karpova T, Sprague BL, McNally JG, Ozato K (2005) Partner-regulated interaction of IFN regulatory factor 8 with chromatin visualized in live macrophages. Proc Natl Acad Sci USA 102:14368–14373

    Article  PubMed  CAS  Google Scholar 

  118. Hida S, Tadachi M, Saito T, Taki S (2005) Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance. Blood 106:2011–2017

    Article  PubMed  CAS  Google Scholar 

  119. Testa U, Stellacci E, Pelosi E, Sestili P, Venditti M, Orsatti R, Fragale A, Petrucci E, Pasquini L, Belardelli F, Gabriele L, Battistini A (2004) Impaired myelopoiesis in mice devoid of interferon regulatory factor 1. Leukemia 18:1864–1871

    Article  PubMed  CAS  Google Scholar 

  120. Milanovic M, Terszowski G, Struck D, Liesenfeld O, Carstanjen D (2008) IFN consensus sequence binding protein (Icsbp) is critical for eosinophil development. J Immunol 181:5045–5053

    PubMed  CAS  Google Scholar 

  121. Duncan GS, Mittrucker HW, Kagi D, Matsuyama T, Mak TW (1996) The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo. J Exp Med 184:2043–2048

    Article  PubMed  CAS  Google Scholar 

  122. Ogasawara K, Hida S, Azimi N, Tagaya Y, Sato T, Yokochi-Fukuda T, Waldmann TA, Taniguchi T, Taki S (1998) Requirement for IRF-1 in the microenvironment supporting development of natural killer cells. Nature 391:700–703

    Article  PubMed  CAS  Google Scholar 

  123. Ohteki T, Yoshida H, Matsuyama T, Duncan GS, Mak TW, Ohashi PS (1998) The transcription factor interferon regulatory factor 1 (IRF-1) is important during the maturation of natural killer 1.1 + T cell receptor-alpha/beta + (NK1 + T) cells, natural killer cells, and intestinal intraepithelial T cells. J Exp Med 187:967–972

    Article  PubMed  CAS  Google Scholar 

  124. Lohoff M, Duncan GS, Ferrick D, Mittrucker HW, Bischof S, Prechtl S, Rollinghoff M, Schmitt E, Pahl A, Mak TW (2000) Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads to severely compromised development of natural killer and T helper type 1 cells. J Exp Med 192:325–336

    Article  PubMed  CAS  Google Scholar 

  125. Taki S, Nakajima S, Ichikawa E, Saito T, Hida S (2005) IFN regulatory factor-2 deficiency revealed a novel checkpoint critical for the generation of peripheral NK cells. J Immunol 174:6005–6012

    PubMed  CAS  Google Scholar 

  126. Wang H, Lee CH, Qi C, Tailor P, Feng J, Abbasi S, Atsumi T, Morse HC 3rd (2008) IRF8 regulates B cell lineage specification, commitment and differentiation. Blood 112(10):4028–4038

    Google Scholar 

  127. Cattoretti G, Shaknovich R, Smith PM, Jack HM, Murty VV, Alobeid B (2006) Stages of germinal center transit are defined by B cell transcription factor coexpression and relative abundance. J Immunol 177:6930–6939

    PubMed  CAS  Google Scholar 

  128. Falini B, Fizzotti M, Pucciarini A, Bigerna B, Marafioti T, Gambacorta M, Pacini R, Alunni C, Natali-Tanci L, Ugolini B, Sebastiani C, Cattoretti G, Pileri S, Dalla-Favera R, Stein H (2000) A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood 95:2084–2092

    PubMed  CAS  Google Scholar 

  129. Sciammas R, Shaffer AL, Schatz JH, Zhao H, Staudt LM, Singh H (2006) Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation. Immunity 25:225–236

    Article  PubMed  CAS  Google Scholar 

  130. Lu R, Medina KL, Lancki DW, Singh H (2003) IRF-4, 8 orchestrate the pre-B-to-B transition in lymphocyte development. Genes Dev 17:1703–1708

    Article  PubMed  CAS  Google Scholar 

  131. Ma S, Turetsky A, Trinh L, Lu R (2006) IFN regulatory factor 4 and 8 promote Ig light chain kappa locus activation in pre-B cell development. J Immunol 177:7898–7904

    PubMed  CAS  Google Scholar 

  132. Marecki S, Fenton MJ (2002) The role of IRF-4 in transcriptional regulation. J Interferon Cytokine Res 22:121–133

    Article  PubMed  CAS  Google Scholar 

  133. Johnson K, Hashimshony T, Sawai CM, Pongubala JM, Skok JA, Aifantis I, Singh H (2008) Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling. Immunity 28:335–345

    Article  PubMed  CAS  Google Scholar 

  134. Lee CH, Melchers M, Wang H, Torrey TA, Slota R, Qi CF, Kim JY, Lugar P, Kong HJ, Farrington L, van der Zouwen B, Zhou JX, Lougaris V, Lipsky PE, Grammer AC, Morse HC III (2006) Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. J Exp Med 203:63–72

    Article  PubMed  CAS  Google Scholar 

  135. Mittrucker HW, Matsuyama T, Grossman A, Kundig TM, Potter J, Shahinian A, Wakeham A, Patterson B, Ohashi PS, Mak TW (1997) Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 275:540–543

    Article  PubMed  CAS  Google Scholar 

  136. Saito M, Gao J, Basso K, Kitagawa Y, Smith PM, Bhagat G, Pernis A, Pasqualucci L, Dalla-Favera R (2007) A signaling pathway mediating downregulation of BCL6 in germinal center B cells is blocked by BCL6 gene alterations in B cell lymphoma. Cancer Cell 12:280–292

    Article  PubMed  CAS  Google Scholar 

  137. Klein U, Casola S, Cattoretti G, Shen Q, Lia M, Mo T, Ludwig T, Rajewsky K, Dalla-Favera R (2006) Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination. Nat Immunol 7:773–782

    Article  PubMed  CAS  Google Scholar 

  138. Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, Kundig TM, Amakawa R, Kishihara K, Wakeham A et al (1993) Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell 75:83–97

    PubMed  CAS  Google Scholar 

  139. White LC, Wright KL, Felix NJ, Ruffner H, Reis LF, Pine R, Ting JP (1996) Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8 + T cells in IRF-1-/- mice. Immunity 5:365–376

    Article  PubMed  CAS  Google Scholar 

  140. Penninger JM, Sirard C, Mittrucker HW, Chidgey A, Kozieradzki I, Nghiem M, Hakem A, Kimura T, Timms E, Boyd R, Taniguchi T, Matsuyama T, Mak TW (1997) The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8 + thymocytes. Immunity 7:243–254

    Article  PubMed  CAS  Google Scholar 

  141. Hida S, Ogasawara K, Sato K, Abe M, Takayanagi H, Yokochi T, Sato T, Hirose S, Shirai T, Taki S, Taniguchi T (2000) CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling. Immunity 13:643–655

    Article  PubMed  CAS  Google Scholar 

  142. Lohoff M, Ferrick D, Mittrucker HW, Duncan GS, Bischof S, Rollinghoff M, Mak TW (1997) Interferon regulatory factor-1 is required for a T helper 1 immune response in vivo. Immunity 6:681–689

    Article  PubMed  CAS  Google Scholar 

  143. Taki S, Sato T, Ogasawara K, Fukuda T, Sato M, Hida S, Suzuki G, Mitsuyama M, Shin EH, Kojima S, Taniguchi T, Asano Y (1997) Multistage regulation of Th1-type immune responses by the transcription factor IRF-1. Immunity 6:673–679

    Article  PubMed  CAS  Google Scholar 

  144. Coccia EM, Passini N, Battistini A, Pini C, Sinigaglia F, Rogge L (1999) Interleukin-12 induces expression of interferon regulatory factor-1 via signal transducer and activator of transcription-4 in human T helper type 1 cells. J Biol Chem 274:6698–6703

    Article  PubMed  CAS  Google Scholar 

  145. Galon J, Sudarshan C, Ito S, Finbloom D, O’Shea JJ (1999) IL-12 induces IFN regulating factor-1 (IRF-1) gene expression in human NK and T cells. J Immunol 162:7256–7262

    PubMed  CAS  Google Scholar 

  146. Kano S, Sato K, Morishita Y, Vollstedt S, Kim S, Bishop K, Honda K, Kubo M, Taniguchi T (2008) The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells. Nat Immunol 9:34–41

    Article  PubMed  CAS  Google Scholar 

  147. Fragale A, Gabriele L, Stellacci E, Borghi P, Perrotti E, Ilari R, Lanciotti A, Remoli AL, Venditti M, Belardelli F, Battistini A (2008) IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression. J Immunol 181:1673–1682

    PubMed  CAS  Google Scholar 

  148. Salkowski CA, Kopydlowski K, Blanco J, Cody MJ, McNally R, Vogel SN (1999) IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. J Immunol 163:1529–1536

    PubMed  CAS  Google Scholar 

  149. Elser B, Lohoff M, Kock S, Giaisi M, Kirchhoff S, Krammer PH, Li-Weber M (2002) IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Immunity 17:703–712

    Article  PubMed  CAS  Google Scholar 

  150. Giese NA, Gabriele L, Doherty TM, Klinman DM, Tadesse-Heath L, Contursi C, Epstein SL, Morse HC III (1997) Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin 12 expression. J Exp Med 186:1535–1546

    Article  PubMed  CAS  Google Scholar 

  151. Scharton-Kersten T, Contursi C, Masumi A, Sher A, Ozato K (1997) Interferon consensus sequence binding protein-deficient mice display impaired resistance to intracellular infection due to a primary defect in interleukin 12 p40 induction. J Exp Med 186:1523–1534

    Article  PubMed  CAS  Google Scholar 

  152. Lohoff M, Mittrucker HW, Prechtl S, Bischof S, Sommer F, Kock S, Ferrick DA, Duncan GS, Gessner A, Mak TW (2002) Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4. Proc Natl Acad Sci USA 99:11808–11812

    Article  PubMed  CAS  Google Scholar 

  153. Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (2002) Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression. J Exp Med 195:1003–1012

    Article  PubMed  CAS  Google Scholar 

  154. Tominaga N, Ohkusu-Tsukada K, Udono H, Abe R, Matsuyama T, Yui K (2003) Development of Th1 and not Th2 immune responses in mice lacking IFN-regulatory factor-4. Int Immunol 15:1–10

    Article  PubMed  CAS  Google Scholar 

  155. Fehr T, Schoedon G, Odermatt B, Holtschke T, Schneemann M, Bachmann MF, Mak TW, Horak I, Zinkernagel RM (1997) 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. J Exp Med 185:921–931

    Article  PubMed  CAS  Google Scholar 

  156. Liu J, Guan X, Tamura T, Ozato K, Ma X (2004) Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein. J Biol Chem 279:55609–55617

    Article  PubMed  CAS  Google Scholar 

  157. Matsuyama T, Grossman A, Mittrucker HW, Siderovski DP, Kiefer F, Kawakami T, Richardson CD, Taniguchi T, Yoshinaga SK, Mak TW (1995) Molecular cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE). Nucleic Acids Res 23:2127–2136

    Article  PubMed  CAS  Google Scholar 

  158. Hu CM, Jang SY, Fanzo JC, Pernis AB (2002) Modulation of T cell cytokine production by interferon regulatory factor-4. J Biol Chem 277:49238–49246

    Article  PubMed  CAS  Google Scholar 

  159. Honma K, Kimura D, Tominaga N, Miyakoda M, Matsuyama T, Yui K (2008) Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells. Proc Natl Acad Sci USA 105:15890–15895

    Article  PubMed  Google Scholar 

  160. Brustle A, Heink S, Huber M, Rosenplanter C, Stadelmann C, Yu P, Arpaia E, Mak TW, Kamradt T, Lohoff M (2007) The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 8:958–966

    Article  PubMed  CAS  Google Scholar 

  161. Chen Q, Yang W, Gupta S, Biswas P, Smith P, Bhagat G, Pernis AB (2008) IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Immunity 29:899–911

    Article  PubMed  CAS  Google Scholar 

  162. Mizutani T, Tsuji K, Ebihara Y, Taki S, Ohba Y, Taniguchi T, Honda K (2008) Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling. Exp Hematol 36:255–264

    Article  PubMed  CAS  Google Scholar 

  163. Essers MA, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, Trumpp A (2009) IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 458:904–908

    Article  PubMed  CAS  Google Scholar 

  164. Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T (2009) Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat Med 15:696–700

    Article  PubMed  CAS  Google Scholar 

  165. Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, Howard E, de Lima RL, Daack-Hirsch S, Sander A, McDonald-McGinn DM, Zackai EH, Lammer EJ, Aylsworth AS, Ardinger HH, Lidral AC, Pober BR, Moreno L, Arcos-Burgos M, Valencia C, Houdayer C, Bahuau M, Moretti-Ferreira D, Richieri-Costa A, Dixon MJ, Murray JC (2002) Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet 32:285–289

    Article  PubMed  CAS  Google Scholar 

  166. Ingraham CR, Kinoshita A, Kondo S, Yang B, Sajan S, Trout KJ, Malik MI, Dunnwald M, Goudy SL, Lovett M, Murray JC, Schutte BC (2006) Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet 38:1335–1340

    Article  PubMed  CAS  Google Scholar 

  167. Richardson RJ, Dixon J, Malhotra S, Hardman MJ, Knowles L, Boot-Handford RP, Shore P, Whitmarsh A, Dixon MJ (2006) Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat Genet 38:1329–1334

    Article  PubMed  CAS  Google Scholar 

  168. Eguchi J, Yan QW, Schones DE, Kamal M, Hsu CH, Zhang MQ, Crawford GE, Rosen ED (2008) Interferon regulatory factors are transcriptional regulators of adipogenesis. Cell Metab 7:86–94

    Article  PubMed  CAS  Google Scholar 

  169. Tanaka N, Ishihara M, Lamphier MS, Nozawa H, Matsuyama T, Mak TW, Aizawa S, Tokino T, Oren M, Taniguchi T (1996) Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage. Nature 382:816–818

    Article  PubMed  CAS  Google Scholar 

  170. Pamment J, Ramsay E, Kelleher M, Dornan D, Ball KL (2002) Regulation of the IRF-1 tumour modifier during the response to genotoxic stress involves an ATM-dependent signalling pathway. Oncogene 21:7776–7785

    Article  PubMed  CAS  Google Scholar 

  171. Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, Lamphier MS, Aizawa S, Mak TW, Taniguchi T (1994) Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell 77:829–839

    Article  PubMed  CAS  Google Scholar 

  172. Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, Matsuyama T, Mak TW, Taki S, Taniguchi T (1995) An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. Nature 376:596–599

    Article  PubMed  CAS  Google Scholar 

  173. Lallemand C, Palmieri M, Blanchard B, Meritet JF, Tovey MG (2002) GAAP-1: a transcriptional activator of p53 and IRF-1 possesses pro-apoptotic activity. EMBO Rep 3:153–158

    Article  PubMed  CAS  Google Scholar 

  174. Kano A, Haruyama T, Akaike T, Watanabe Y (1999) IRF-1 is an essential mediator in IFN-gamma-induced cell cycle arrest and apoptosis of primary cultured hepatocytes. Biochem Biophys Res Commun 257:672–677

    Article  PubMed  CAS  Google Scholar 

  175. Kim EJ, Lee JM, Namkoong SE, Um SJ, Park JS (2002) Interferon regulatory factor-1 mediates interferon-gamma-induced apoptosis in ovarian carcinoma cells. J Cell Biochem 85:369–380

    Article  PubMed  CAS  Google Scholar 

  176. Tomita Y, Bilim V, Hara N, Kasahara T, Takahashi K (2003) Role of IRF-1 and caspase-7 in IFN-gamma enhancement of Fas-mediated apoptosis in ACHN renal cell carcinoma cells. Int J Cancer 104:400–408

    Article  PubMed  CAS  Google Scholar 

  177. Passioura T, Dolnikov A, Shen S, Symonds G (2005) N-ras-induced growth suppression of myeloid cells is mediated by IRF-1. Cancer Res 65:797–804

    PubMed  CAS  Google Scholar 

  178. Nozawa H, Oda E, Nakao K, Ishihara M, Ueda S, Yokochi T, Ogasawara K, Nakatsuru Y, Shimizu S, Ohira Y, Hioki K, Aizawa S, Ishikawa T, Katsuki M, Muto T, Taniguchi T, Tanaka N (1999) Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53. Genes Dev 13:1240–1245

    Article  PubMed  CAS  Google Scholar 

  179. Tan RS, Taniguchi T, Harada H (1996) Identification of the lysyl oxidase gene as target of the antioncogenic transcription factor, IRF-1, and its possible role in tumor suppression. Cancer Res 56:2417–2421

    PubMed  CAS  Google Scholar 

  180. Jeay S, Pianetti S, Kagan HM, Sonenshein GE (2003) Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B. Mol Cell Biol 23:2251–2263

    Article  PubMed  CAS  Google Scholar 

  181. Willman CL, Sever CE, Pallavicini MG, Harada H, Tanaka N, Slovak ML, Yamamoto H, Harada K, Meeker TC, List AF et al (1993) Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. Science 259:968–971

    Article  PubMed  CAS  Google Scholar 

  182. Ogasawara S, Tamura G, Maesawa C, Suzuki Y, Ishida K, Satoh N, Uesugi N, Saito K, Satodate R (1996) Common deleted region on the long arm of chromosome 5 in esophageal carcinoma. Gastroenterology 110:52–57

    Article  PubMed  CAS  Google Scholar 

  183. Tamura G, Ogasawara S, Nishizuka S, Sakata K, Maesawa C, Suzuki Y, Terashima M, Saito K, Satodate R (1996) Two distinct regions of deletion on the long arm of chromosome 5 in differentiated adenocarcinomas of the stomach. Cancer Res 56:612–615

    PubMed  CAS  Google Scholar 

  184. Nozawa H, Oda E, Ueda S, Tamura G, Maesawa C, Muto T, Taniguchi T, Tanaka N (1998) Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer. Int J Cancer 77:522–527

    Article  PubMed  CAS  Google Scholar 

  185. Park J, Kim K, Lee EJ, Seo YJ, Lim SN, Park K, Rho SB, Lee SH, Lee JH (2007) Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis. Proc Natl Acad Sci USA 104:17028–17033

    Article  PubMed  Google Scholar 

  186. Harada H, Kondo T, Ogawa S, Tamura T, Kitagawa M, Tanaka N, Lamphier MS, Hirai H, Taniguchi T (1994) Accelerated exon skipping of IRF-1 mRNA in human myelodysplasia/leukemia; a possible mechanism of tumor suppressor inactivation. Oncogene 9:3313–3320

    PubMed  CAS  Google Scholar 

  187. Tzoanopoulos D, Speletas M, Arvanitidis K, Veiopoulou C, Kyriaki S, Thyphronitis G, Sideras P, Kartalis G, Ritis K (2002) Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia. Br J Haematol 119:46–53

    Article  PubMed  CAS  Google Scholar 

  188. Kondo T, Minamino N, Nagamura-Inoue T, Matsumoto M, Taniguchi T, Tanaka N (1997) Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity. Oncogene 15:1275–1281

    Article  PubMed  CAS  Google Scholar 

  189. Hao SX, Ren R (2000) Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in Bcr-Abl-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr-Abl-induced myeloproliferative disorder. Mol Cell Biol 20:1149–1161

    Article  PubMed  CAS  Google Scholar 

  190. Schmidt M, Hochhaus A, Konig-Merediz SA, Brendel C, Proba J, Hoppe GJ, Wittig B, Ehninger G, Hehlmann R, Neubauer A (2000) Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy. J Clin Oncol 18:3331–3338

    PubMed  CAS  Google Scholar 

  191. Ortmann CA, Burchert A, Holzle K, Nitsche A, Wittig B, Neubauer A, Schmidt M (2005) Down-regulation of interferon regulatory factor 4 gene expression in leukemic cells due to hypermethylation of CpG motifs in the promoter region. Nucleic Acids Res 33:6895–6905

    Article  PubMed  CAS  Google Scholar 

  192. Deng M, Daley GQ (2001) Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia. Blood 97:3491–3497

    Article  PubMed  CAS  Google Scholar 

  193. Liu K, Abrams SI (2003) Coordinate regulation of IFN consensus sequence-binding protein and caspase-1 in the sensitization of human colon carcinoma cells to Fas-mediated apoptosis by IFN-gamma. J Immunol 170:6329–6337

    PubMed  CAS  Google Scholar 

  194. Huang W, Zhu C, Wang H, Horvath E, Eklund EA (2008) The interferon consensus sequence-binding protein (ICSBP/IRF8) represses PTPN13 gene transcription in differentiating myeloid cells. J Biol Chem 283:7921–7935

    Article  PubMed  CAS  Google Scholar 

  195. Yang D, Thangaraju M, Greeneltch K, Browning DD, Schoenlein PV, Tamura T, Ozato K, Ganapathy V, Abrams SI, Liu K (2007) Repression of IFN regulatory factor 8 by DNA methylation is a molecular determinant of apoptotic resistance and metastatic phenotype in metastatic tumor cells. Cancer Res 67:3301–3309

    Article  PubMed  CAS  Google Scholar 

  196. Lee KY, Geng H, Ng KM, Yu J, van Hasselt A, Cao Y, Zeng YX, Wong AH, Wang X, Ying J, Srivastava G, Lung ML, Wang LD, Kwok TT, Levi BZ, Chan AT, Sung JJ, Tao Q (2008) Epigenetic disruption of interferon-gamma response through silencing the tumor suppressor interferon regulatory factor 8 in nasopharyngeal, esophageal and multiple other carcinomas. Oncogene 27:5267–5276

    Article  PubMed  CAS  Google Scholar 

  197. Mori T, Anazawa Y, Iiizumi M, Fukuda S, Nakamura Y, Arakawa H (2002) Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53. Oncogene 21:2914–2918

    Article  PubMed  CAS  Google Scholar 

  198. Barnes BJ, Kellum MJ, Pinder KE, Frisancho JA, Pitha PM (2003) Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death. Cancer Res 63:6424–6431

    PubMed  CAS  Google Scholar 

  199. Hu G, Mancl ME, Barnes BJ (2005) Signaling through IFN regulatory factor-5 sensitizes p53-deficient tumors to DNA damage-induced apoptosis and cell death. Cancer Res 65:7403–7412

    Article  PubMed  CAS  Google Scholar 

  200. Couzinet A, Tamura K, Chen HM, Nishimura K, Wang Z, Morishita Y, Takeda K, Yagita H, Yanai H, Taniguchi T, Tamura T (2008) A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis. Proc Natl Acad Sci USA 105:2556–2561

    Article  PubMed  Google Scholar 

  201. Bailey CM, Abbott DE, Margaryan NV, Khalkhali-Ellis Z, Hendrix MJ (2008) Interferon regulatory factor 6 promotes cell cycle arrest and is regulated by the proteasome in a cell cycle-dependent manner. Mol Cell Biol 28:2235–2243

    Article  PubMed  CAS  Google Scholar 

  202. Heylbroeck C, Balachandran S, Servant MJ, DeLuca C, Barber GN, Lin R, Hiscott J (2000) The IRF-3 transcription factor mediates Sendai virus-induced apoptosis. J Virol 74:3781–3792

    Article  PubMed  CAS  Google Scholar 

  203. Weaver BK, Ando O, Kumar KP, Reich NC (2001) Apoptosis is promoted by the dsRNA-activated factor (DRAF1) during viral infection independent of the action of interferon or p53. FASEB J 15:501–515

    Article  PubMed  CAS  Google Scholar 

  204. Kirshner JR, Karpova AY, Kops M, Howley PM (2005) Identification of TRAIL as an interferon regulatory factor 3 transcriptional target. J Virol 79:9320–9324

    Article  PubMed  CAS  Google Scholar 

  205. Hsu LC, Park JM, Zhang K, Luo JL, Maeda S, Kaufman RJ, Eckmann L, Guiney DG, Karin M (2004) The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428:341–345

    Article  PubMed  CAS  Google Scholar 

  206. Kim T, Kim TY, Song YH, Min IM, Yim J, Kim TK (1999) Activation of interferon regulatory factor 3 in response to DNA-damaging agents. J Biol Chem 274:30686–30689

    Article  PubMed  CAS  Google Scholar 

  207. Karpova AY, Trost M, Murray JM, Cantley LC, Howley PM (2002) Interferon regulatory factor-3 is an in vivo target of DNA-PK. Proc Natl Acad Sci USA 99:2818–2823

    Article  PubMed  CAS  Google Scholar 

  208. Duguay D, Mercier F, Stagg J, Martineau D, Bramson J, Servant M, Lin R, Galipeau J, Hiscott J (2002) In vivo interferon regulatory factor 3 tumor suppressor activity in B16 melanoma tumors. Cancer Res 62:5148–5152

    PubMed  CAS  Google Scholar 

  209. Kim TY, Lee KH, Chang S, Chung C, Lee HW, Yim J, Kim TK (2003) Oncogenic potential of a dominant negative mutant of interferon regulatory factor 3. J Biol Chem 278:15272–15278

    Article  PubMed  CAS  Google Scholar 

  210. Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T (2003) Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 424:516–523

    Article  PubMed  CAS  Google Scholar 

  211. Weihua X, Lindner DJ, Kalvakolanu DV (1997) The interferon-inducible murine p48 (ISGF3gamma) gene is regulated by protooncogene c-myc. Proc Natl Acad Sci USA 94:7227–7232

    Article  PubMed  CAS  Google Scholar 

  212. Harada H, Kitagawa M, Tanaka N, Yamamoto H, Harada K, Ishihara M, Taniguchi T (1993) Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2. Science 259:971–974

    Article  PubMed  CAS  Google Scholar 

  213. Passioura T, Shen S, Symonds G, Dolnikov A (2005) A retroviral library genetic screen identifies IRF-2 as an inhibitor of N-ras-induced growth suppression in leukemic cells. Oncogene 24:7327–7336

    Article  PubMed  CAS  Google Scholar 

  214. Nguyen H, Mustafa A, Hiscott J, Lin R (1995) Transcription factor IRF-2 exerts its oncogenic phenotype through the DNA binding/transcription repression domain. Oncogene 11:537–544

    PubMed  CAS  Google Scholar 

  215. Yamamoto H, Lamphier MS, Fujita T, Taniguchi T, Harada H (1994) The oncogenic transcription factor IRF-2 possesses a transcriptional repression and a latent activation domain. Oncogene 9:1423–1428

    PubMed  CAS  Google Scholar 

  216. Vaughan PS, Aziz F, van Wijnen AJ, Wu S, Harada H, Taniguchi T, Soprano KJ, Stein JL, Stein GS (1995) Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2. Nature 377:362–365

    Article  PubMed  CAS  Google Scholar 

  217. Vaughan PS, van der Meijden CM, Aziz F, Harada H, Taniguchi T, van Wijnen AJ, Stein JL, Stein GS (1998) Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2. J Biol Chem 273:194–199

    Article  PubMed  CAS  Google Scholar 

  218. Masumi A, Yamakawa Y, Fukazawa H, Ozato K, Komuro K (2003) Interferon regulatory factor-2 regulates cell growth through its acetylation. J Biol Chem 278:25401–25407

    Article  PubMed  CAS  Google Scholar 

  219. Yamagata T, Nishida J, Tanaka S, Sakai R, Mitani K, Yoshida M, Taniguchi T, Yazaki Y, Hirai H (1996) A novel interferon regulatory factor family transcription factor, ICSAT/Pip/LSIRF, that negatively regulates the activity of interferon-regulated genes. Mol Cell Biol 16:1283–1294

    PubMed  CAS  Google Scholar 

  220. Mamane Y, Grandvaux N, Hernandez E, Sharma S, Innocente SA, Lee JM, Azimi N, Lin R, Hiscott J (2002) Repression of IRF-4 target genes in human T cell leukemia virus-1 infection. Oncogene 21:6751–6765

    Article  PubMed  CAS  Google Scholar 

  221. Mamane Y, Loignon M, Palmer J, Hernandez E, Cesaire R, Alaoui-Jamali M, Hiscott J (2005) Repression of DNA repair mechanisms in IRF-4-expressing and HTLV-I-infected T lymphocytes. J Interferon Cytokine Res 25:43–51

    Article  PubMed  CAS  Google Scholar 

  222. Feldman AL, Law M, Remstein ED, Macon WR, Erickson LA, Grogg KL, Kurtin PJ, Dogan A. 2008. Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia 23(3):574–580

    Google Scholar 

  223. Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, Chaganti RS, Dalla-Favera R (1997) Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma. Nat Genet 17:226–230

    Article  PubMed  CAS  Google Scholar 

  224. Heintel D, Zojer N, Schreder M, Strasser-Weippl K, Kainz B, Vesely M, Gisslinger H, Drach J, Gaiger A, Jager U, Ludwig H (2008) Expression of MUM1/IRF4 mRNA as a prognostic marker in patients with multiple myeloma. Leukemia 22:441–445

    Article  PubMed  CAS  Google Scholar 

  225. Shaffer AL, Emre NC, Lamy L, Ngo VN, Wright G, Xiao W, Powell J, Dave S, Yu X, Zhao H, Zeng Y, Chen B, Epstein J, Staudt LM (2008) IRF4 addiction in multiple myeloma. Nature 454:226–231

    Article  PubMed  CAS  Google Scholar 

  226. Saito T, Yamagata T, Takahashi T, Honda H, Hirai H (1999) ICSAT overexpression is not sufficient to cause adult T-cell leukemia or multiple myeloma. Biochem Biophys Res Commun 260:329–331

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We apologize to all of the authors whose invaluable work we could not discuss or cite in this review due to space constraints. We thank Drs. H. Negishi and M. Nakasato for valuable discussions and help. This work was supported by Kakenhi (Grant-in-Aid for Scientific Research) on Priority Areas “Integrative Research Toward the Conquest of Cancer” and by Global Center of Excellence Program “Integrative Life Science Based on the Study of Biosignaling Mechanisms”, from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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  1. Department of Immunology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan

    David Savitsky, Tomohiko Tamura, Hideyuki Yanai & Tadatsugu Taniguchi

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  1. David Savitsky
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  2. Tomohiko Tamura
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Correspondence to Tadatsugu Taniguchi.

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Savitsky, D., Tamura, T., Yanai, H. et al. Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother 59, 489–510 (2010). https://doi.org/10.1007/s00262-009-0804-6

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