Genomes and Genes
Gene Symbol: Irf2
Description: interferon regulatory factor 2
Alias: 9830146E22Rik, AI646973, Irf-2, interferon regulatory factor 2
- Driggers P, Ennist D, Gleason S, Mak W, Marks M, Levi B, et al. An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A. 1990;87:3743-7 pubmed..The presence of multiple factors that bind common IFN response motifs may partly account for the complexity and diversity of IFN action as well as IFN-regulated gene expression. ..
- Tanaka N, Taniguchi T. Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system. Adv Immunol. 1992;52:263-81 pubmed
- Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T. Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat Med. 2009;15:696-700 pubmed publisher..induce proliferation and exhaustion in hematopoietic stem cells (HSCs) and that interferon regulatory factor-2 (IRF2), a transcriptional suppressor of type I IFN signaling5, 6, preserves the self-renewal and multilineage ..
- Vaughan P, van der Meijden C, Aziz F, Harada H, Taniguchi T, van Wijnen A, et al. Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2. J Biol Chem. 1998;273:194-9 pubmed..We have previously shown that the transcription factor interferon regulatory factor 2 (IRF-2) can activate histone H4 gene expression...
- Fehr T, Schoedon G, Odermatt B, Holtschke T, Schneemann M, Bachmann M, et al. 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. 1997;185:921-31 pubmed..ICSBP-/- and to a lesser degree also IRF2-/- mice were highly susceptible to Listeria infection...
- Salkowski C, Barber S, Detore G, Vogel S. Differential dysregulation of nitric oxide production in macrophages with targeted disruptions in IFN regulatory factor-1 and -2 genes. J Immunol. 1996;156:3107-10 pubmed..synthase mRNA in response to IFN-gamma and LPS. These results indicate that IRF-1 and IRF-2 differ in their mechanism of NO. regulation and that IRF-2 regulates inducible NO. synthase post-transcriptionally. ..
- Mamane Y, Heylbroeck C, Genin P, Algarte M, Servant M, Lepage C, et al. Interferon regulatory factors: the next generation. Gene. 1999;237:1-14 pubmed..The aim of this review is to provide an update on the novel discoveries in the area of IRF transcription factors and the important roles of the new generation of IRFs--particularly IRF-3, IRF-4 and IRF-7. ..
- Salkowski C, Kopydlowski K, Blanco J, Cody M, McNally R, Vogel S. IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. J Immunol. 1999;163:1529-36 pubmed..These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production. ..
- Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, et al. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell. 1993;75:83-97 pubmed..IRF-2-deficient mice exhibited bone marrow suppression of hematopoiesis and B lymphopoiesis and mortality following lymphocytic choriomeningitis virus infection. ..
- Barber S, Fultz M, Salkowski C, Vogel S. Differential expression of interferon regulatory factor 1 (IRF-1), IRF-2, and interferon consensus sequence binding protein genes in lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive macrophages. Infect Immun. 1995;63:601-8 pubmed..Thus, the IRFs may represent yet an additional molecular pathway in the complex response to LPS. ..
- Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, et al. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989;58:729-39 pubmed..Our results suggest that transcription of the IFN and IFN-inducible genes is regulated by two similar trans-acting factors that apparently compete for the same cis-acting recognition sequences, but which have opposite effects. ..
- Ko J, Gendron Fitzpatrick A, Splitter G. Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis. J Immunol. 2002;168:2433-40 pubmed
- Hida S, Tadachi M, Saito T, Taki S. Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance. Blood. 2005;106:2011-7 pubmed..Here we show that naive mice lacking the transcription factor, interferon regulatory factor 2 (IRF-2), exhibited signal transducer and activator of transcription 6 (Stat6)-independent expansion of ..
- Kim E, Park J, Um S. Ubc9-mediated sumoylation leads to transcriptional repression of IRF-1. Biochem Biophys Res Commun. 2008;377:952-6 pubmed publisher..Taken together, these observations suggest that Ubc9 functions as a transcriptional repressor of IRF-1 by inducing sumoylation, and that this effect may be required for the physiological activity of IRF-1. ..
- Masumi A, Yamakawa Y, Fukazawa H, Ozato K, Komuro K. Interferon regulatory factor-2 regulates cell growth through its acetylation. J Biol Chem. 2003;278:25401-7 pubmed..These results indicate that IRF-2 is acetylated in a cell growth-dependent manner, which enables it to contribute to transcription of cell growth-regulated promoters. ..
- Blackburn J, Ohazama A, Kawasaki K, Otsuka Tanaka Y, Liu B, Honda K, et al. The role of Irf6 in tooth epithelial invagination. Dev Biol. 2012;365:61-70 pubmed publisher..Irf6 thus also plays a critical role in regulating epithelial invagination. In addition, we also found that canonical Wnt signaling is upregulated in evaginated incisor epithelium of both Ikk? and Irf6 mutant embryos. ..
- Ashkar A, Black G, Wei Q, He H, Liang L, Head J, et al. Assessment of requirements for IL-15 and IFN regulatory factors in uterine NK cell differentiation and function during pregnancy. J Immunol. 2003;171:2937-44 pubmed..These studies indicate that uNK cell development and maturation share some aspects with NK cell development in other tissues, but also display distinctive tissue-specific regulation. ..
- Minamino K, Takahara K, Adachi T, Nagaoka K, Iyoda T, Taki S, et al. IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms. Int Immunol. 2012;24:573-81 pubmed publisher..These results revealed a multi-faceted role of IRF-2 in the function of B cells, particularly B2 cells, through regulating proliferation in an IFNAR-dependent manner and antibody production via up-regulation of Blimp-1. ..
- Uegaki K, Shirakawa M, Fujita T, Taniguchi T, Kyogoku Y. Characterization of the DNA binding domain of the mouse IRF-2 protein. Protein Eng. 1993;6:195-200 pubmed..These results showed that this peptide fragment, IRF-2(113), may be a good material for investigation of the DNA binding domain of IRF-2 and of the DNA-protein interaction. ..
- Sato T, Ikeda M, Yotsumoto S, Shimada Y, Higuchi T, Kobayashi H, et al. Novel interferon-based pre-transplantation conditioning in the treatment of a congenital metabolic disorder. Blood. 2013;121:3267-73 pubmed publisher..active type I IFN signaling in HSC recipients was further demonstrated using mice lacking IFN regulatory factor 2 (IRF2), a transcriptional suppressor of type I IFN signaling...
- Notake T, Horisawa S, Sanjo H, Miyagawa S, Hida S, Taki S. Differential requirements for IRF-2 in generation of CD1d-independent T cells bearing NK cell receptors. J Immunol. 2012;188:4838-45 pubmed publisher..The influence of IRF-2 deficiency on Ly49(+) memory phenotype T cells observed in this study suggested a unique transcriptional program for this T cell population among other NKR(+) T and memory phenotype T cells. ..
- Hayashi H, Kohno T, Yasui K, Murota H, Kimura T, Duncan G, et al. Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription. Proc Natl Acad Sci U S A. 2011;108:18766-71 pubmed publisherMice deficient for interferon regulatory factor (Irf)2 (Irf2(-/-) mice) exhibit immunological abnormalities and cannot survive lymphocytic choriomeningitis virus infection...
- Klune J, Dhupar R, Kimura S, Ueki S, Cardinal J, Nakao A, et al. Interferon regulatory factor-2 is protective against hepatic ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2012;303:G666-73 pubmed publisher..No strategies to mitigate IRF1-mediated liver damage exist. IRF2 is a structurally similar endogenous protein that competes with IRF1 for DNA binding sites in IRF-responsive target ..
- Liljeroos M, Vuolteenaho R, Rounioja S, Henriques Normark B, Hallman M, Ojaniemi M. Bacterial ligand of TLR2 signals Stat activation via induction of IRF1/2 and interferon-alpha production. Cell Signal. 2008;20:1873-81 pubmed publisher..Here, we studied the involvement of IRF1 and IRF2 in TLR2-mediated responses...
- Prakash K, Kumar P, Mukherjee S, Rath P. Chimeric murine interferon regulatory factor-2 (IRF-2) binds to IRF-E (IRF binding element), VRE? (virus response element) but not to VRE?1. Cell Biochem Funct. 2014;32:630-6 pubmed publisher..This study is first of its kind and paves the way to understand the differential DNA binding and molecular mechanism of DNA binding activity of the IRF-2 molecule, which is crucial for its function(s). ..
- Ichikawa E, Hida S, Omatsu Y, Shimoyama S, Takahara K, Miyagawa S, et al. Defective development of splenic and epidermal CD4+ dendritic cells in mice deficient for IFN regulatory factor-2. Proc Natl Acad Sci U S A. 2004;101:3909-14 pubmed..Our current findings thus pointed to a previously unknown unique cell-type-selective multimode function of IRF-2 in the regulation of lymphohematopoiesis. ..
- Sun L, Jiang Z, Acosta Rodriguez V, Berger M, Du X, Choi J, et al. HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections. J Exp Med. 2017;214:3263-3277 pubmed publisher..an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors...
- Cuesta N, Salkowski C, Thomas K, Vogel S. Regulation of lipopolysaccharide sensitivity by IFN regulatory factor-2. J Immunol. 2003;170:5739-47 pubmed..Collectively, these findings reveal a critical role for IRF-2 in endotoxicity, and point to a previously unappreciated role for IRF-2 in the regulation of apoptosis. ..
- Xie R, Van Wijnen A, van der Meijden C, Stein J, Stein G. Forced expression of the interferon regulatory factor 2 oncoprotein causes polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cells. Cancer Res. 2002;62:2510-5 pubmed..Our data suggest that the IRF-2 oncoprotein regulates a critical cell cycle checkpoint that controls progression through G2 and mitosis in FDC-P1 hematopoietic progenitor cells. ..
- Horiuchi M, Koike G, Yamada T, Mukoyama M, Nakajima M, Dzau V. The growth-dependent expression of angiotensin II type 2 receptor is regulated by transcription factors interferon regulatory factor-1 and -2. J Biol Chem. 1995;270:20225-30 pubmed..We speculate that these transcriptional factors influence cell growth in part by regulating AT2 receptor expression. ..
- Honda K, Mizutani T, Taniguchi T. Negative regulation of IFN-alpha/beta signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells. Proc Natl Acad Sci U S A. 2004;101:2416-21 pubmed
- Huang X, Nandakumar V, Tumurkhuu G, Wang T, Jiang X, Hong B, et al. Mysm1 is required for interferon regulatory factor expression in maintaining HSC quiescence and thymocyte development. Cell Death Dis. 2016;7:e2260 pubmed publisher..We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at ..
- Blanco J, Contursi C, Salkowski C, DeWitt D, Ozato K, Vogel S. Interferon regulatory factor (IRF)-1 and IRF-2 regulate interferon gamma-dependent cyclooxygenase 2 expression. J Exp Med. 2000;191:2131-44 pubmed..Our data demonstrate conclusively the importance of IFN-gamma as a direct activator and coactivator of the Cox-2 gene, and the central role of IRF-1/2 family members in this process. ..
- Kuo T, Calame K. B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites. J Immunol. 2004;173:5556-63 pubmed..Thus, our data suggest that Blimp-1 competes in vivo with a subset of IRF proteins and help predict the sites and IRF family members that may be affected. ..
- Zhang S, Thomas K, Blanco J, Salkowski C, Vogel S. The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro. J Endotoxin Res. 2002;8:379-88 pubmed..Collectively, these data provide evidence for an important role for IRF-1 in vivo and in vitro and for IRF-2 in vitro in the regulation of COX-2 expression by LPS. ..
- Gudjonsson J, Johnston A, Dyson M, Valdimarsson H, Elder J. Mouse models of psoriasis. J Invest Dermatol. 2007;127:1292-308 pubmed..In this review, we describe various animal models, detail the immunologic and intracellular pathways that mediate these phenotypes and assess the utility of these models to better understand this disease. ..
- Riego E, Perez A, Martinez R, Castro F, Lleonart R, de la Fuente J. Differential constitutive expression of interferon genes in early mouse embryos. Mol Reprod Dev. 1995;41:157-66 pubmed..Mu IFN-alpha A and a new Mu IFN-alpha species (Mu IFN-alpha 12) were isolated from (D-) P19 cells. The presence of constitutive IFN-alpha transcripts in early mouse embryos suggests a role for these molecules during embryogenesis. ..
- Cai Y, Wang W, Yang Y, Sun L, Teitelbaum D, Yang H. Up-regulation of intestinal epithelial cell derived IL-7 expression by keratinocyte growth factor through STAT1/IRF-1, IRF-2 pathway. PLoS ONE. 2013;8:e58647 pubmed publisher..KGF could up-regulate IL-7 expression through the STAT1/IRF-1, IRF-2 signaling pathway, which is a new insight in potential effects of KGF on the intestinal mucosal immune system. ..
- Masumi A, Hamaguchi I, Kuramitsu M, Mizukami T, Takizawa K, Momose H, et al. Interferon regulatory factor-2 induces megakaryopoiesis in mouse bone marrow hematopoietic cells. FEBS Lett. 2009;583:3493-500 pubmed publisher..The number of CD41-positive bone marrow cells increased in mice injected with IRF-2-expressing bone marrow cells. These findings suggest that IRF-2 plays an important role in megakaryopoiesis in inflammatory states. ..
- Mashima H, Sato T, Horie Y, Nakagawa Y, Kojima I, Ohteki T, et al. Interferon regulatory factor-2 regulates exocytosis mechanisms mediated by SNAREs in pancreatic acinar cells. Gastroenterology. 2011;141:1102-1113.e1-8 pubmed publisher..We investigated the role of interferon regulatory factor-2 (IRF2) in exocytosis in pancreatic acinar cells...
- Lohoff M, Duncan G, Ferrick D, Mittrucker H, Bischof S, Prechtl S, et al. 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. 2000;192:325-36 pubmed..Mechanistically, IRF-2 may act as a functional agonist rather than antagonist of IRF-1 for some, but not all, IFN-stimulated regulatory element (ISRE)-responsive genes. ..
- Li W, Nagineni C, Efiok B, Chepelinsky A, Egwuagu C. Interferon regulatory transcription factors are constitutively expressed and spatially regulated in the mouse lens. Dev Biol. 1999;210:44-55 pubmed
- Xi H, Goodwin B, Shepherd A, Blanck G. Impaired class II transactivator expression in mice lacking interferon regulatory factor-2. Oncogene. 2001;20:4219-27 pubmed..These data indicate that IRF-2, like IRF-1, plays a critical role in the regulation of the endogenous CIITA gene. The implications in understanding the previously described phenotypes of IRF-2 defective mice are discussed. ..
- Taki S, Nakajima S, Ichikawa E, Saito T, Hida S. IFN regulatory factor-2 deficiency revealed a novel checkpoint critical for the generation of peripheral NK cells. J Immunol. 2005;174:6005-12 pubmed..The differential peripheral and central NK cell deficiencies in IRF-2(-/-) mice thus revealed a novel late checkpoint for NK cell maturation, distinct from the early IL-15-dependent expansion stage. ..
- Fujii Y, Shimizu T, Kusumoto M, Kyogoku Y, Taniguchi T, Hakoshima T. Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences. EMBO J. 1999;18:5028-41 pubmed..Our results provide new insights into the structure and function of this family of transcription factors. ..
- Kawakami T, Matsumoto M, Sato M, Harada H, Taniguchi T, Kitagawa M. Possible involvement of the transcription factor ISGF3 gamma in virus-induced expression of the IFN-beta gene. FEBS Lett. 1995;358:225-9 pubmed..These results suggest that ISGF3 gamma or complex containing ISGF3 gamma is involved in the IRF-1-independent pathway mediating IFN-beta gene regulation. ..
- Sul O, Lee H, Kim W, Choi J, Kwak J, Choi Y, et al. Regulation of the murine TR2/HVEM gene expression by IRF. Biochem Biophys Res Commun. 2008;367:277-83 pubmed..Transfection of IRF-2 expression plasmid and of dominant negative IRF-2 mutant further confirmed our results. Together, these data demonstrate that IRF-2 is involved in the regulation of TR2 expression in EL-4 T cells. ..
- Li M, Bozzacco L, Hoffmann H, Breton G, Loschko J, Xiao J, et al. Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion. J Exp Med. 2016;213:2931-2947 pubmed..In this study, we demonstrate that IFN regulatory factor 2 (IRF2), an ISG and a negative regulator of IFN signaling, influences alphavirus neuroinvasion and pathogenesis...
- Cuesta N, Nhu Q, Zudaire E, Polumuri S, Cuttitta F, Vogel S. IFN regulatory factor-2 regulates macrophage apoptosis through a STAT1/3- and caspase-1-dependent mechanism. J Immunol. 2007;178:3602-11 pubmed..Collectively, these data support the hypothesis that IRF-2 acts as a transcriptional repressor of Casp1, and that the absence of IRF-2 renders macrophages more sensitive to apoptotic stimuli in a caspase-1-dependent process. ..
- Mizutani T, Tsuji K, Ebihara Y, Taki S, Ohba Y, Taniguchi T, et al. Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling. Exp Hematol. 2008;36:255-64 pubmed publisher..type I interferon (IFN) is known to inhibit erythropoiesis, we studied mice deficient in the gene for interferon regulatory factor 2 (IRF2), which functions as a negative regulator of type I IFN signaling, in the context of ..
- Hida S, Ogasawara K, Sato K, Abe M, Takayanagi H, Yokochi T, et al. CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling. Immunity. 2000;13:643-55 pubmed..IRF-2 may represent a unique negative regulator, attenuating IFN-alpha/beta-induced gene transcription, which is necessary for balancing the beneficial and harmful effects of IFN-alpha/beta signaling in the immune system. ..
- Furui J, Uegaki K, Yamazaki T, Shirakawa M, Swindells M, Harada H, et al. Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family. Structure. 1998;6:491-500 pubmed..The evidence here implies that the evolutional pathway of the IRF family is distinct from that of the other wHTH proteins, in other words, the immune system diverged from an evolutional stem at an early stage. ..
- Chung M, Kawamoto S. IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene expression during phorbol ester-induced promyelocytic HL-60 differentiation. J Biol Chem. 2004;279:56042-52 pubmed..Together, these results indicate that IRF-2 contributes to transcriptional activation of the NMHC-A gene via 32kb-150 during TPA-induced differentiation of HL-60 cells. ..
- Arakura F, Hida S, Ichikawa E, Yajima C, Nakajima S, Saida T, et al. Genetic control directed toward spontaneous IFN-alpha/IFN-beta responses and downstream IFN-gamma expression influences the pathogenesis of a murine psoriasis-like skin disease. J Immunol. 2007;179:3249-57 pubmed