IRF-3

Summary

Gene Symbol: IRF-3
Description: interferon regulatory factor 3
Alias: IIAE7, interferon regulatory factor 3
Species: human
Products:     IRF-3

Top Publications

  1. Peters K, Smith H, Stark G, Sen G. IRF-3-dependent, NFkappa B- and JNK-independent activation of the 561 and IFN-beta genes in response to double-stranded RNA. Proc Natl Acad Sci U S A. 2002;99:6322-7 pubmed
    ..Therefore, IRF-3 activation by dsRNA is sufficient to induce the transcription of genes with simple promoters such as 561 as well as complex promoters such as IFN-beta. ..
  2. Liang Q, Deng H, Li X, Wu X, Tang Q, Chang T, et al. Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7. J Immunol. 2011;187:4754-63 pubmed publisher
    ..Collectively, our results suggest that TRIM28 is a specific SUMO E3 ligase and negative regulator of IRF7. ..
  3. Lin R, Noyce R, Collins S, Everett R, Mossman K. The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes. J Virol. 2004;78:1675-84 pubmed
    ..Furthermore, we demonstrate that HSV-1 modifies the IRF3 pathway in a manner different from that of the small RNA viruses most commonly studied. ..
  4. Ran Y, Liu T, Zhou Q, Li S, Mao A, Li Y, et al. SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation. J Mol Cell Biol. 2011;3:283-92 pubmed publisher
  5. Shinobu N, Iwamura T, Yoneyama M, Yamaguchi K, Suhara W, Fukuhara Y, et al. Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory factor 3 by lipopolysaccharide. FEBS Lett. 2002;517:251-6 pubmed
    ..These results highlight cross-talk between TLR-mediated and virus/dsRNA-induced signals resulting in activation of the IFN system. ..
  6. Fitzgerald K, McWhirter S, Faia K, Rowe D, Latz E, Golenbock D, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol. 2003;4:491-6 pubmed
    The transcription factors interferon regulatory factor 3 (IRF3) and NF-kappaB are required for the expression of many genes involved in the innate immune response...
  7. Shu C, Yi G, Watts T, Kao C, Li P. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nat Struct Mol Biol. 2012;19:722-4 pubmed publisher
    ..Guanines of c-di-GMP stack against the phenolic rings of a conserved tyrosine, and mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling. ..
  8. Chattopadhyay S, Marques J, Yamashita M, Peters K, Smith K, Desai A, et al. Viral apoptosis is induced by IRF-3-mediated activation of Bax. EMBO J. 2010;29:1762-73 pubmed publisher
    ..Thus, IRF-3 is a dual-action cytoplasmic protein that, upon activation, translocates to the nucleus or to the mitochondrion and triggers two complementary antiviral responses of the infected cell. ..
  9. Nakhaei P, Mesplede T, Solis M, Sun Q, Zhao T, Yang L, et al. The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation. PLoS Pathog. 2009;5:e1000650 pubmed publisher
    ..Thus, Triad3A represents a versatile E3 ubiquitin ligase that negatively regulates RIG-like receptor signaling by targeting TRAF3 for degradation following RNA virus infection. ..

More Information

Publications94

  1. Tokunaga T, Naruke Y, Shigematsu S, Kohno T, Yasui K, Ma Y, et al. Aberrant expression of interferon regulatory factor 3 in human lung cancer. Biochem Biophys Res Commun. 2010;397:202-7 pubmed publisher
    We analyzed the subcellular distributions and gene structures of interferon regulatory factor 3 (IRF3) transcription factor in 50 cases of human primary lung cancer...
  2. Mangino G, Percario Z, Fiorucci G, Vaccari G, Manrique S, Romeo G, et al. In vitro treatment of human monocytes/macrophages with myristoylated recombinant Nef of human immunodeficiency virus type 1 leads to the activation of mitogen-activated protein kinases, IkappaB kinases, and interferon regulatory factor 3 and to the r. J Virol. 2007;81:2777-91 pubmed
    ..In addition, we have observed the activation of interferon regulatory factor 3, leading to the synthesis of beta interferon mRNA and protein, which in turn induces STAT2 ..
  3. Abate D, Watanabe S, Mocarski E. Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response. J Virol. 2004;78:10995-1006 pubmed
    ..By subverting IRF-3, the virus escapes throwing a central alarm devoted to both immediate antiviral control and regulation of the immune response. ..
  4. Escalante C, Nistal Villán E, Shen L, Garcia Sastre A, Aggarwal A. Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer. Mol Cell. 2007;26:703-16 pubmed
    b>Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the assembly of the mammalian interferon-beta (IFN-beta) enhanceosome...
  5. Suh H, Zhao M, Rivieccio M, Choi S, Connolly E, Zhao Y, et al. Astrocyte indoleamine 2,3-dioxygenase is induced by the TLR3 ligand poly(I:C): mechanism of induction and role in antiviral response. J Virol. 2007;81:9838-50 pubmed
    ..PIC induction of IDO was mediated in part by IFN-beta but not IFN-gamma, and both NF-kappaB and interferon regulatory factor 3 (IRF3) were required...
  6. Collins S, Noyce R, Mossman K. Innate cellular response to virus particle entry requires IRF3 but not virus replication. J Virol. 2004;78:1706-17 pubmed
  7. Sharma S, tenOever B, Grandvaux N, Zhou G, Lin R, Hiscott J. Triggering the interferon antiviral response through an IKK-related pathway. Science. 2003;300:1148-51 pubmed
    ..These studies illustrate an essential role for an IKK-related kinase pathway in triggering the host antiviral response to viral infection. ..
  8. Wang Q, Nagarkar D, Bowman E, Schneider D, Gosangi B, Lei J, et al. Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. J Immunol. 2009;183:6989-97 pubmed publisher
    ..These results suggest that TLR3 and MDA5, but not RIG-I, are required for maximal sensing of RV dsRNA and that TLR3 and MDA5 signal through a common downstream signaling intermediate, IRF3. ..
  9. Mori M, Yoneyama M, Ito T, Takahashi K, Inagaki F, Fujita T. Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation. J Biol Chem. 2004;279:9698-702 pubmed
    ..These results strongly suggest that Ser-386 is the target of the IRF-3 kinase and critical determinant for the activation of IRF-3. ..
  10. Sarkar S, Peters K, Elco C, Sakamoto S, Pal S, Sen G. Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling. Nat Struct Mol Biol. 2004;11:1060-7 pubmed
    ..Thus, the PI3K-Akt pathway plays an essential role in TLR3-mediated gene induction. ..
  11. Honda K, Takaoka A, Taniguchi T. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity. 2006;25:349-60 pubmed
    ..Here, we summarize the recent studies on IRFs, providing a paradigm of how genes are ingeniously regulated during immune responses. We also consider some evolutional aspects on the IFN-IRF system. ..
  12. Okumura A, Alce T, Lubyova B, Ezelle H, Strebel K, Pitha P. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation. Virology. 2008;373:85-97 pubmed
    ..These data implicate Vif and Vpr in the disruption of the initial antiviral response and point to the need of HIV-1 to circumvent the antiviral response during the very early phase of replication. ..
  13. Zhong B, Yang Y, Li S, Wang Y, Li Y, Diao F, et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity. 2008;29:538-50 pubmed publisher
    ..Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity. ..
  14. Kumar K, McBride K, Weaver B, Dingwall C, Reich N. Regulated nuclear-cytoplasmic localization of interferon regulatory factor 3, a subunit of double-stranded RNA-activated factor 1. Mol Cell Biol. 2000;20:4159-68 pubmed
    ..DRAF1 is a multimeric transcription factor containing the interferon regulatory factor 3 (IRF-3) protein and one of the histone acetyl transferases, CREB binding protein (CBP) or p300 (CBP/..
  15. Doehle B, Hladik F, McNevin J, McElrath M, Gale M. Human immunodeficiency virus type 1 mediates global disruption of innate antiviral signaling and immune defenses within infected cells. J Virol. 2009;83:10395-405 pubmed publisher
    b>Interferon regulatory factor 3 (IRF-3) is essential for innate intracellular immune defenses that limit virus replication, but these defenses fail to suppress human immunodeficiency virus (HIV) infection, which can ultimately associate ..
  16. Soulat D, Burckstummer T, Westermayer S, Goncalves A, Bauch A, Stefanovic A, et al. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J. 2008;27:2135-46 pubmed publisher
    ..Phosphorylation-deficient mutants of DDX3X failed to synergize with TBK1 in their ability to stimulate the IFN promoter. Overall, our data imply that DDX3X is a critical effector of TBK1 that is necessary for type I IFN induction. ..
  17. Doyle S, Vaidya S, O Connell R, Dadgostar H, Dempsey P, Wu T, et al. IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity. 2002;17:251-63 pubmed
    ..of several primary response genes was dependent on NF-kappaB, commonly activated by several TLRs, and interferon regulatory factor 3 (IRF3), which was found to confer TLR3/TLR4 specificity...
  18. Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, et al. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell. 2010;141:315-30 pubmed publisher
    ..Our results delineate the mechanism of RIG-I activation, identify CARD domains as a ubiquitin sensor, and demonstrate that unanchored K63-polyubiquitin chains are signaling molecules in antiviral innate immunity...
  19. Wang Y, Tong X, Omoregie E, Liu W, Meng S, Ye X. Tetraspanin 6 (TSPAN6) negatively regulates retinoic acid-inducible gene I-like receptor-mediated immune signaling in a ubiquitination-dependent manner. J Biol Chem. 2012;287:34626-34 pubmed publisher
    ..We concluded that TSPAN6 functions as a negative regulator of the RLR pathway by interacting with MAVS in a ubiquitination-dependent manner. ..
  20. Zhang M, Tian Y, Wang R, Gao D, Zhang Y, Diao F, et al. Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3. Cell Res. 2008;18:1096-104 pubmed publisher
    ..These findings suggest that the cellular antiviral response is controlled by a negative feedback regulatory mechanism involving RBCK1-mediated ubiquitination and degradation of IRF3. ..
  21. Gao D, Wu J, Wu Y, Du F, Aroh C, Yan N, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science. 2013;341:903-6 pubmed publisher
    ..These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses. ..
  22. Higgs R, Ní Gabhann J, Ben Larbi N, Breen E, Fitzgerald K, Jefferies C. The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. J Immunol. 2008;181:1780-6 pubmed
    ..Collectively, this demonstrates a novel role for Ro52 in turning off and thus limiting IRF3-dependent type I IFN production by targeting the transcription factor for polyubiquitination and subsequent proteasomal degradation. ..
  23. Fitzgerald K, Rowe D, Barnes B, Caffrey D, Visintin A, Latz E, et al. LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med. 2003;198:1043-55 pubmed
    ..These studies suggest that TRIF and TRAM both function in LPS-TLR4 signaling to regulate the MyD88-independent pathway during the innate immune response to LPS. ..
  24. Lin R, Mamane Y, Hiscott J. Structural and functional analysis of interferon regulatory factor 3: localization of the transactivation and autoinhibitory domains. Mol Cell Biol. 1999;19:2465-74 pubmed
    The interferon regulatory factor 3 (IRF-3) gene encodes a 55-kDa protein which is expressed constitutively in all tissues...
  25. Peters K, Chattopadhyay S, Sen G. IRF-3 activation by Sendai virus infection is required for cellular apoptosis and avoidance of persistence. J Virol. 2008;82:3500-8 pubmed publisher
    ..These results demonstrated that in our model system, IRF-3 controlled the fate of the SeV-infected cells by promoting apoptosis and preventing persistence...
  26. Gu L, Fullam A, BRENNAN R, Schröder M. Human DEAD box helicase 3 couples I?B kinase ? to interferon regulatory factor 3 activation. Mol Cell Biol. 2013;33:2004-15 pubmed publisher
    ..Here we show that DDX3 mediates phosphorylation of interferon regulatory factor 3 (IRF3) by the kinase IKK?...
  27. Reimer T, Brcic M, Schweizer M, Jungi T. poly(I:C) and LPS induce distinct IRF3 and NF-kappaB signaling during type-I IFN and TNF responses in human macrophages. J Leukoc Biol. 2008;83:1249-57 pubmed publisher
    ..Thus, in human macrophages, poly(I:C) treatment induces a distinct cytokine response when compared with murine macrophages. Additionally, a robust IFN-beta response can be induced in the absence of detectable IRF3 activation. ..
  28. Fredericksen B, Gale M. West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling. J Virol. 2006;80:2913-23 pubmed publisher
    ..We have previously shown that West Nile virus NY (WNV-NY) delays activation of interferon regulatory factor 3 (IRF-3), a transcription factor critical to the initiation of the antiviral response...
  29. Qin B, Liu C, Lam S, Srinath H, Delston R, Correia J, et al. Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation. Nat Struct Biol. 2003;10:913-21 pubmed
  30. Servant M, Grandvaux N, tenOever B, Duguay D, Lin R, Hiscott J. Identification of the minimal phosphoacceptor site required for in vivo activation of interferon regulatory factor 3 in response to virus and double-stranded RNA. J Biol Chem. 2003;278:9441-7 pubmed
    ..The inability of the phosphospecific antibody to detect Ser(396) phosphorylation in lipopolysaccharide-treated cells suggests that other major pathways may be involved in IRF-3 activation following Toll-like receptor 4 stimulation. ..
  31. Otsuka M, Kato N, Moriyama M, Taniguchi H, Wang Y, Dharel N, et al. Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses. Hepatology. 2005;41:1004-12 pubmed publisher
    ..roles in TLR3-mediated IFN-beta production through the activation of the transcriptional factor interferon regulatory factor 3 (IRF-3)...
  32. Fredericksen B, Smith M, Katze M, Shi P, Gale M. The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway. J Virol. 2004;78:7737-47 pubmed
    ..Although the activation of the IRF-3 pathway was not sufficient to block virus replication, our results suggest that IRF-3 target genes function to constrain WNV infection and limit cell-to-cell virus spread. ..
  33. Chen W, Srinath H, Lam S, Schiffer C, Royer W, Lin K. Contribution of Ser386 and Ser396 to activation of interferon regulatory factor 3. J Mol Biol. 2008;379:251-60 pubmed publisher
    ..These results indicate that Ser386 and Ser396 are critical for IRF-3 activation, and support a phosphorylation-oligomerization model for IRF-3 activation. ..
  34. Tsitoura E, Thomas J, Cuchet D, Thoinet K, Mavromara P, Epstein A. Infection with herpes simplex type 1-based amplicon vectors results in an IRF3/7-dependent, TLR-independent activation of the innate antiviral response in primary human fibroblasts. J Gen Virol. 2009;90:2209-20 pubmed publisher
    ..Therefore, our results confirm the existence of TLR-independent, IRF3/7-dependent activation pathways triggered by HSV-1 particles in human fibroblasts. ..
  35. Au W, Moore P, Lowther W, Juang Y, Pitha P. Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. Proc Natl Acad Sci U S A. 1995;92:11657-61 pubmed
    ..Identification of this ISRE-binding protein may help us to understand the specificity in the various Stat pathways. ..
  36. Wang L, Li S, Dorf M. NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses. PLoS ONE. 2012;7:e43756 pubmed publisher
    ..The combined results refine current views of RLR signaling, define the role of TBK1 polyubiquitination, and detail the mechanisms involved in signalosome assembly...
  37. Lin R, Heylbroeck C, Pitha P, Hiscott J. Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol Cell Biol. 1998;18:2986-96 pubmed
  38. Kim H, Seed B. The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3. Nat Immunol. 2010;11:743-50 pubmed publisher
    ..Higher expression of MafB in human pancreatic islet beta cells might increase cellular vulnerability to viral infections associated with the etiology of type 1 diabetes. ..
  39. Mibayashi M, Martinez Sobrido L, Loo Y, Cardenas W, Gale M, Garcia Sastre A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J Virol. 2007;81:514-24 pubmed
    ..Our results indicate that, in addition to sequestering dsRNA, the NS1 of influenza A virus binds to RIG-I and inhibits downstream activation of IRF-3, preventing the transcriptional induction of IFN-beta. ..
  40. Smith E, Marie I, Prakash A, Garcia Sastre A, Levy D. IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein. J Biol Chem. 2001;276:8951-7 pubmed
  41. Tarassishin L, Loudig O, Bauman A, Shafit Zagardo B, Suh H, Lee S. Interferon regulatory factor 3 inhibits astrocyte inflammatory gene expression through suppression of the proinflammatory miR-155 and miR-155*. Glia. 2011;59:1911-22 pubmed publisher
    ..b>Interferon regulatory factor 3 (IRF3) is a transcription factor required for IFN? production and antiviral immunity...
  42. Bergstroem B, Johnsen I, Nguyen T, Hagen L, Slupphaug G, Thommesen L, et al. Identification of a novel in vivo virus-targeted phosphorylation site in interferon regulatory factor-3 (IRF3). J Biol Chem. 2010;285:24904-14 pubmed publisher
    ..Taken together, our results show that IRF3 is subject to multiple interdependent phosphorylations, and we identify Thr(390) as a novel in vivo phosphorylation site that modulates the phosphorylation status of TBK1-targeted Ser(396). ..
  43. Everett R, Young D, Randall R, Orr A. STAT-1- and IRF-3-dependent pathways are not essential for repression of ICP0-null mutant herpes simplex virus type 1 in human fibroblasts. J Virol. 2008;82:8871-81 pubmed publisher
    ..interferon signaling in the phenotype of ICP0-null mutant HSV-1, we isolated HFs depleted of STAT-1 or interferon regulatory factor 3 (IRF-3). Surprisingly, plaque formation by the mutant virus was not improved in either cell type...
  44. Chattopadhyay S, Fensterl V, Zhang Y, Veleeparambil M, Yamashita M, Sen G. Role of interferon regulatory factor 3-mediated apoptosis in the establishment and maintenance of persistent infection by Sendai virus. J Virol. 2013;87:16-24 pubmed publisher
    ..The key proapoptotic protein in this pathway is interferon regulatory factor 3 (IRF-3), which upon activation by virus infection binds BAX, translocates it to mitochondria, and ..
  45. Panne D, McWhirter S, Maniatis T, Harrison S. Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch. J Biol Chem. 2007;282:22816-22 pubmed
    The transcription factor interferon regulatory factor 3 (IRF-3) regulates genes in the innate immune response. IRF-3 is activated through phosphorylation by the kinases IKK epsilon and/or TBK1...
  46. Yoneyama M, Suhara W, Fujita T. Control of IRF-3 activation by phosphorylation. J Interferon Cytokine Res. 2002;22:73-6 pubmed
  47. Long L, Deng Y, Yao F, Guan D, Feng Y, Jiang H, et al. Recruitment of phosphatase PP2A by RACK1 adaptor protein deactivates transcription factor IRF3 and limits type I interferon signaling. Immunity. 2014;40:515-29 pubmed publisher
    ..Therefore, dephosphorylation of IRF3 is a deactivation mechanism that contributes to termination of IRF3-type I IFN signaling. ..
  48. Joung S, Park Z, Rani S, Takeuchi O, Akira S, Lee J. Akt contributes to activation of the TRIF-dependent signaling pathways of TLRs by interacting with TANK-binding kinase 1. J Immunol. 2011;186:499-507 pubmed publisher
    ..To our knowledge, our results demonstrate a new regulatory mechanism for Akt activation mediated by TBK1 and a novel role of Akt in TLR-mediated immune responses. ..
  49. Suh H, Zhao M, Choi N, Belbin T, Brosnan C, Lee S. TLR3 and TLR4 are innate antiviral immune receptors in human microglia: role of IRF3 in modulating antiviral and inflammatory response in the CNS. Virology. 2009;392:246-59 pubmed publisher
    ..We suggest that a balanced expression between inflammatory and innate immune genes might be achieved by IRF3 over-expression. ..
  50. Yoneyama M, Suhara W, Fukuhara Y, Fukuda M, Nishida E, Fujita T. Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300. EMBO J. 1998;17:1087-95 pubmed
    ..These findings suggest that IRF-3 plays an important role in the virus-inducible primary activation of type I IFN and IFN-responsive genes. ..
  51. Genin P, Lin R, Hiscott J, Civas A. Differential regulation of human interferon A gene expression by interferon regulatory factors 3 and 7. Mol Cell Biol. 2009;29:3435-50 pubmed publisher
    ..IFN-A) gene cluster is modulated following paramyxovirus infection by the relative amounts of active interferon regulatory factor 3 (IRF-3) and IRF-7...
  52. Qin B, Liu C, Srinath H, Lam S, Correia J, Derynck R, et al. Crystal structure of IRF-3 in complex with CBP. Structure. 2005;13:1269-77 pubmed
    ..The finding suggests a possible regulatory mechanism in CBP/p300, by which the interacting transcription factor can specify the coactivator's conformation and influence the transcriptional outcome. ..
  53. Chen H, Sun H, You F, Sun W, Zhou X, Chen L, et al. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell. 2011;147:436-46 pubmed publisher
    ..Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum...
  54. Sasai M, Shingai M, Funami K, Yoneyama M, Fujita T, Matsumoto M, et al. NAK-associated protein 1 participates in both the TLR3 and the cytoplasmic pathways in type I IFN induction. J Immunol. 2006;177:8676-83 pubmed
    ..Both the cytoplasmic and TLR3-mediated dsRNA recognition pathways converge upon NAP1 for the activation of the IRF-3 and IFN-beta promoter. ..
  55. Melroe G, Silva L, Schaffer P, Knipe D. Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: Potential role in blocking IFN-beta induction. Virology. 2007;360:305-21 pubmed
    ..Therefore, ICP0 provides an example of how viruses can block IFN-beta induction by sequestration of important transcription factors essential for the host response. ..
  56. Zeng W, Xu M, Liu S, Sun L, Chen Z. Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell. 2009;36:315-25 pubmed publisher
    ..Furthermore, we show that replacement of endogenous ubiquitin with its K63R mutant abolishes viral activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in IRF3 activation. ..
  57. Prinarakis E, Chantzoura E, Thanos D, Spyrou G. S-glutathionylation of IRF3 regulates IRF3-CBP interaction and activation of the IFN beta pathway. EMBO J. 2008;27:865-75 pubmed publisher
    b>Interferon regulatory factor 3 (IRF3) is an essential transcriptional regulator of the interferon genes. IRF3 is constitutively present in a latent conformation in the cell cytoplasm...
  58. Saitoh T, Tun Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, et al. Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1. Nat Immunol. 2006;7:598-605 pubmed
    ..These results elucidate a previously unknown mechanism for controlling innate antiviral responses by negatively regulating IRF3 activity via Pin1. ..
  59. Bibeau Poirier A, Gravel S, Clément J, Rolland S, Rodier G, Coulombe P, et al. Involvement of the IkappaB kinase (IKK)-related kinases tank-binding kinase 1/IKKi and cullin-based ubiquitin ligases in IFN regulatory factor-3 degradation. J Immunol. 2006;177:5059-67 pubmed
  60. Ordureau A, Enesa K, Nanda S, Le François B, Peggie M, Prescott A, et al. DEAF1 is a Pellino1-interacting protein required for interferon production by Sendai virus and double-stranded RNA. J Biol Chem. 2013;288:24569-80 pubmed publisher
    ..3 (TLR3), induces the TANK-Binding Kinase 1 (TBK1)-dependent phosphorylation and activation of Interferon Regulatory Factor 3 (IRF3) and the E3 ubiquitin ligase Pellino1, which are required for interferon β (IFNβ) gene ..
  61. Servant M, ten Oever B, Lepage C, Conti L, Gessani S, Julkunen I, et al. Identification of distinct signaling pathways leading to the phosphorylation of interferon regulatory factor 3. J Biol Chem. 2001;276:355-63 pubmed
    ..The failure of numerous well characterized pharmacological inhibitors to abrogate virus-induced IRF-3 phosphorylation suggests the involvement of a novel kinase activity in IRF-3 regulation by viruses. ..
  62. Suhara W, Yoneyama M, Iwamura T, Yoshimura S, Tamura K, Namiki H, et al. Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP/p300. J Biochem. 2000;128:301-7 pubmed
    ..We previously reported that IRF-3 (interferon regulatory factor 3) is specifically phosphorylated on serine residues and directly transmits a virus-induced signal from ..
  63. Shi H, Yang K, Liu X, Liu X, Wei B, Shan Y, et al. Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. Mol Cell Biol. 2010;30:2424-36 pubmed publisher
    ..Transcription factor interferon regulatory factor 3 (IRF3) plays a pivotal role and is tightly regulated in this process...
  64. Cui J, Li Y, Zhu L, Liu D, Songyang Z, Wang H, et al. NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4. Nat Immunol. 2012;13:387-95 pubmed publisher
    ..Our results identify a previously unrecognized role for NLRP4 in the regulation of type I interferon signaling and provide molecular insight into the mechanisms by which NLRP4-DTX4 targets TBK1 for degradation. ..
  65. Sen N, Sommer M, Che X, White K, Ruyechan W, Arvin A. Varicella-zoster virus immediate-early protein 62 blocks interferon regulatory factor 3 (IRF3) phosphorylation at key serine residues: a novel mechanism of IRF3 inhibition among herpesviruses. J Virol. 2010;84:9240-53 pubmed publisher
    ..Thus, IE62 has two critical but discrete roles following VZV entry: to induce expression of VZV genes and to disarm the IFN-dependent antiviral defense through a novel mechanism that prevents IRF3 phosphorylation. ..
  66. Devaraj S, Wang N, Chen Z, Chen Z, Tseng M, Barretto N, et al. Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J Biol Chem. 2007;282:32208-21 pubmed
    ..Our data suggest that regulation of IRF-3-dependent innate antiviral defenses by PLpro may contribute to the establishment of SARS-CoV infection. ..
  67. Clément J, Bibeau Poirier A, Gravel S, Grandvaux N, Bonneil E, Thibault P, et al. Phosphorylation of IRF-3 on Ser 339 generates a hyperactive form of IRF-3 through regulation of dimerization and CBP association. J Virol. 2008;82:3984-96 pubmed publisher
    ..Importantly, our study establishes a molecular link between the role of serine 339 in IRF-3 homodimerization, CBP association, and its destabilization. ..
  68. Zhang B, Li M, Chen L, Yang K, Shan Y, Zhu L, et al. The TAK1-JNK cascade is required for IRF3 function in the innate immune response. Cell Res. 2009;19:412-28 pubmed publisher
    ..Thus, this study demonstrates that the TAK1-JNK cascade is required for IRF3 function, in addition to TBK1/IKKvarepsilon, uncovering a new mechanism for mitogen-activated protein (MAP) kinase to regulate the innate immunity. ..
  69. Hou F, Sun L, Zheng H, Skaug B, Jiang Q, Chen Z. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell. 2011;146:448-61 pubmed publisher
    ..These results suggest that a prion-like conformational switch of MAVS activates and propagates the antiviral signaling cascade. ..
  70. tenOever B, Servant M, Grandvaux N, Lin R, Hiscott J. Recognition of the measles virus nucleocapsid as a mechanism of IRF-3 activation. J Virol. 2002;76:3659-69 pubmed
    ..Altogether, this study suggests that IRF-3 recognizes nucleocapsid structures during the course of an MeV infection and triggers the induction of interferon production. ..
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    ..Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFN? production by targeting the TBK1 signaling complex. ..
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    b>Interferon regulatory factor 3 (IRF3) plays a crucial role in mediating cellular responses to virus intrusion. The protein kinase TBK1 is a key regulator inducing phosphorylation of IRF3...
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    On detecting viral RNAs, the RNA helicase retinoic acid-inducible gene I (RIG-I) activates the interferon regulatory factor 3 (IRF3) signalling pathway to induce type I interferon (IFN) gene transcription...
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    ..In particular, interferon regulatory factor 3 (IRF3) has been shown to be essential for the induction of an antiviral response...
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    ..Therefore, we propose a model for the rapid induction of IFN-? in monocytes, whereby IRF8 and PU.1 form a scaffold complex on the IFN-? promoter to facilitate the recruitment of IRF3, thus enabling rapid IFN-? transcription. ..
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    ..These observations provide a unique example of the coordinate activation of multiple transcriptional activator proteins and their highly cooperative assembly into a transcriptional enhancer complex in vivo...
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    ..Altogether, these data further highlight the respective functions of IRF-3 and IRF-7 to program apoptotic, immune and anti-tumor responses. ..
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    ..Two of the components of DRAF1 have now been identified as interferon regulatory factor 3 (IRF-3) and the transcriptional coactivator CREB-binding protein (CBP)/p300...
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    ..adaptor protein STING (stimulator of IFN genes), which activates the transcription factor interferon regulatory factor 3 (IRF3); however, how STING activates IRF3 is unclear...
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    ..Collectively, these studies suggest that the ability of bICP0 to reduce IRF3 protein levels is important with respect to disarming the IFN response during productive infection...
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    ..We propose that the ULD is a regulatory component of the TBK1/IKK-i kinases involved in the control of the kinase activation, substrate presentation and downstream signaling pathways. ..
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    ..These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling. ..
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    ..Our findings suggest that MIP-T3 functions as a negative regulator of innate IFN response by preventing TRAF3 from forming protein complexes with critical downstream transducers and effectors. ..
  85. Akahoshi M, Nakashima H, Sadanaga A, Miyake K, Obara K, Tamari M, et al. Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus. Lupus. 2008;17:568-74 pubmed publisher
    ..In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE. ..