Regulation of immunity and oncogenesis by the IRF transcription factor family (original) (raw)

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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