Genomes and Genes
Gene Symbol: IRF-3
Description: interferon regulatory factor 3
Alias: IIAE7, interferon regulatory factor 3
- 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. ..
- 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...
- Gu L, Fullam A, BRENNAN R, Schröder M. Human DEAD box helicase 3 couples IκB kinase ε 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 IKKε...
- 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...
- 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)...
- 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...
- 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. ..
- 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....
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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 ..
- 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 publisherb>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...
- 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. ..
- 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. ..
- 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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Friedman C, O Donnell M, Legarda Addison D, Ng A, Cardenas W, Yount J, et al. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Rep. 2008;9:930-6 pubmed publisherOn 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...
- Lee Y, Song B, Park C, Kwon K. TRIM11 negatively regulates IFNβ production and antiviral activity by targeting TBK1. PLoS ONE. 2013;8:e63255 pubmed publisher..Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex. ..
- Wathelet M, Lin C, Parekh B, Ronco L, Howley P, Maniatis T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell. 1998;1:507-18 pubmed..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...
- Goubau D, Romieu Mourez R, Solis M, Hernandez E, Mesplede T, Lin R, et al. Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7. Eur J Immunol. 2009;39:527-40 pubmed publisher..Altogether, these data further highlight the respective functions of IRF-3 and IRF-7 to program apoptotic, immune and anti-tumor responses. ..
- Li P, Wong J, Sum C, Sin W, Ng K, Koh M, et al. IRF8 and IRF3 cooperatively regulate rapid interferon-β induction in human blood monocytes. Blood. 2011;117:2847-54 pubmed publisher..Therefore, we propose a model for the rapid induction of IFN-β in monocytes, whereby IRF8 and PU.1 form a scaffold complex on the IFN-β promoter to facilitate the recruitment of IRF3, thus enabling rapid IFN-β transcription. ..
- Weaver B, Kumar K, Reich N. Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol Cell Biol. 1998;18:1359-68 pubmed..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...
- Saira K, Zhou Y, Jones C. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 and, consequently, inhibits beta interferon promoter activity. J Virol. 2007;81:3077-86 pubmed publisher..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...
- Ikeda F, Hecker C, Rozenknop A, Nordmeier R, Rogov V, Hofmann K, et al. Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. EMBO J. 2007;26:3451-62 pubmed..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. ..
- Ng M, Ho T, Kok K, Siu K, Li J, Jin D. MIP-T3 is a negative regulator of innate type I IFN response. J Immunol. 2011;187:6473-82 pubmed publisher..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. ..
- Xu L, Wang Y, Han K, Li L, Zhai Z, Shu H. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19:727-40 pubmed..These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling. ..
- 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. ..