Affinage

IRF2

Interferon regulatory factor 2 · UniProt P14316

Length
349 aa
Mass
39.4 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRF2 is a winged helix-turn-helix transcription factor that functions as both a transcriptional repressor and activator, serving as a central modulator of interferon signaling, innate immune gene expression, cell cycle control, and immune cell differentiation. IRF2 binds the same ISRE/IRF-E consensus elements as the activator IRF1 with virtually indistinguishable affinity and represses IFN-stimulated genes by competitive promoter occupancy and through a C-terminal repression domain, while a latent activation domain enables it to directly activate transcription of histone H4, GSDMD, CASP4, CIITA, and MHC-I pathway genes (PMID:2475256, PMID:7687740, PMID:8152803, PMID:7566094, PMID:31113851, PMID:31471524). Its activity is modulated by phosphorylation (PKA, PKC, CK2), SUMOylation via PIASy that enhances repressor function, and Mdm2-mediated ubiquitination (PMID:9213219, PMID:18514056, PMID:19032150). In vivo, IRF2 is essential for attenuating type I IFN signaling to maintain homeostatic erythropoiesis, colonic stem cell renewal, B lymphopoiesis, nonclassical monocyte development, and NK/CD8+ T cell homeostasis; within tumors, sustained IFN-driven IRF2 expression in CD8+ T cells promotes the exhaustion transcriptional program, and its deletion restores effector function and long-term tumor control (PMID:8402903, PMID:11114377, PMID:18207304, PMID:32901054, PMID:37607223, PMID:36370712).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 High

    The discovery that IRF2 binds the same IFN regulatory elements as IRF1 yet functions as a repressor established the paradigm of antagonistic IRF pairing in IFN gene regulation.

    Evidence cDNA cloning with DNA binding and transcriptional reporter competition assays in Cell

    PMID:2475256

    Open questions at the time
    • Repression mechanism not resolved — competitive displacement vs. active silencing unclear
    • No in vivo validation at this stage
  2. 1993 High

    Demonstration that IRF1 and IRF2 recognize virtually identical DNA sequences, combined with the phenotype of IRF2 knockout mice showing exaggerated IFN induction and impaired hematopoiesis, proved that IRF2 is a physiological brake on IFN signaling and hematopoietic homeostasis in vivo.

    Evidence PCR-assisted binding site selection (EMSA) and targeted gene disruption in mice

    PMID:7687740 PMID:8402903

    Open questions at the time
    • Cell-type-specific contributions of IRF2 not resolved
    • Mechanism linking IFN derepression to bone marrow suppression unknown
  3. 1994 High

    Mapping of a C-terminal repression domain and a latent central activation domain within IRF2 resolved how a single factor can act as both repressor and context-dependent activator.

    Evidence Deletion mapping and LexA fusion transcriptional assays

    PMID:8152803

    Open questions at the time
    • Corepressor/coactivator identity unknown
    • Whether both domains function simultaneously or are context-switched not determined
  4. 1995 High

    Identification of IRF2 as the long-sought histone H4 activator HiNF-M revealed that IRF2 has bona fide transcriptional activator function at a cell cycle–regulated promoter, fundamentally expanding its role beyond IFN repression.

    Evidence Protein purification from HeLa nuclei, identity confirmation, EMSA, and transcriptional reporter assays

    PMID:7566094

    Open questions at the time
    • Cell cycle–dependent regulation of IRF2 activity not mechanistically explained
    • Chromatin context of activation not addressed
  5. 1997 High

    Demonstration that IRF2 is phosphorylated in vivo and selectively targeted by PKA, PKC, and CK2 in vitro established post-translational modification as a regulatory layer for IRF2 activity.

    Evidence In vivo 32P labeling, immunoprecipitation, in vitro kinase assays, 2D phosphopeptide mapping

    PMID:9213219

    Open questions at the time
    • Functional consequence of specific phosphorylation events on DNA binding or transcription not determined
    • In vivo kinase-IRF2 relationships not validated genetically
  6. 1998 High

    NMR determination of the IRF2 DNA-binding domain structure revealed a winged helix-turn-helix fold and identified specific residues mediating DNA recognition, providing the first atomic-resolution understanding of IRF-DNA interaction.

    Evidence NMR spectroscopy of the IRF2 DBD

    PMID:9562558

    Open questions at the time
    • Full-length IRF2 structure not solved
    • Co-crystal with DNA not obtained at this point
  7. 1998 High

    Rescue of histone H4 cell cycle regulation by IRF2 re-expression in knockout fibroblasts demonstrated that IRF2 is required, not merely sufficient, for coupling H4 transcription to S-phase entry.

    Evidence IRF2 KO fibroblasts synchronized in culture with complementation rescue

    PMID:9417064

    Open questions at the time
    • Direct mechanism linking IRF2 to cell cycle machinery not identified
    • Whether IRF2 senses cell cycle signals directly or via upstream regulation unknown
  8. 2000 High

    Genetic epistasis showing that CD8+ T cell and skin disease phenotypes of IRF2 KO mice are rescued by loss of IFN-α/β pathway genes firmly placed IRF2 as a negative regulator of type I IFN signaling in vivo, and loss of IRF2 in macrophages derepressed COX-2 through direct promoter binding, expanding the target repertoire.

    Evidence Double-KO genetic epistasis in mice; ChIP and EMSA on COX-2 promoter in KO macrophages

    PMID:10859338 PMID:11114377

    Open questions at the time
    • Whether IRF2 regulates type I IFN signaling transcriptionally or post-transcriptionally not fully dissected
    • COX-2 regulation not tested in non-macrophage lineages
  9. 2008 Medium

    Identification of SUMOylation by PIASy (enhancing repressor function) and ubiquitination by Mdm2, together with the physical interaction with RelA/p65 promoting NF-κB nuclear translocation, revealed a multi-layered post-translational regulatory network controlling IRF2 activity and expanded its role beyond classical IRF-E targets.

    Evidence In vivo SUMOylation assays with site mutagenesis; reconstituted in vitro Mdm2-dependent ubiquitination; co-IP of IRF2-RelA and NF-κB reporter assays with siRNA knockdown

    PMID:18395009 PMID:18514056 PMID:19032150

    Open questions at the time
    • Physiological triggers for SUMOylation and ubiquitination unknown
    • RelA interaction not validated by reciprocal endogenous co-IP in multiple cell types
    • Functional interplay between SUMOylation and ubiquitination not tested
  10. 2008 High

    Genetic epistasis (Irf2−/−;Ifnar1−/− double KO) rescuing the erythropoiesis defect of IRF2 KO mice established that IRF2 maintains homeostatic erythropoiesis specifically by attenuating type I IFN receptor signaling in erythroid progenitors.

    Evidence Double-KO mice with flow cytometric analysis of erythroid progenitors and Bcl-XL measurement

    PMID:18207304

    Open questions at the time
    • Direct IRF2 target genes in erythroid progenitors not identified
    • Whether IRF2 acts cell-autonomously in erythroid cells not formally proven with conditional KO
  11. 2015 Medium

    ChIP studies showing constitutive IRF2 occupancy at the TLR3 promoter maintaining open chromatin with active histone marks, and interaction with the BAF remodeling complex, revealed a chromatin-architectural role for IRF2 at baseline that primes gene expression prior to IFN stimulation.

    Evidence ChIP for IRF2 and histone marks, BAF complex interaction assays, IRF1/IRF2 KO cell expression analysis

    PMID:25960866

    Open questions at the time
    • BAF subunit specificity for IRF2 interaction not determined
    • Genome-wide extent of this chromatin-priming role unknown
  12. 2017 High

    HCFC2 was identified as a cofactor required for IRF2 binding to the Tlr3 promoter and a large subset of IRF2-dependent IFN-regulated genes, revealing that IRF2 promoter occupancy is not solely determined by its intrinsic DNA-binding properties but requires accessory factors.

    Evidence ENU mutagenesis screen in mice, ChIP for IRF2 at Tlr3 promoter with and without HCFC2, macrophage poly(I:C) response and viral survival assays

    PMID:28320935 PMID:28970238

    Open questions at the time
    • Structural basis of HCFC2-IRF2 interaction not resolved
    • Whether HCFC2 dependency is universal for all IRF2 targets unknown
  13. 2019 High

    Convergent forward genetic and CRISPR screens established IRF2 as a direct transcriptional activator of GSDMD and CASP4, two essential executors of pyroptosis, and of MHC-I pathway components (immunoproteasomes, TAP, ERAP1), while simultaneously repressing PD-L1 and CXCL3, placing IRF2 at a regulatory nexus of innate immunity, antigen presentation, and tumor immune evasion.

    Evidence ENU screen and ChIP/mutagenesis for GSDMD; CRISPR screen in human monocytes for CASP4; CRISPR screen in HeLa for MHC-I pathway; KRAS-driven CRC models for CXCL3 axis

    PMID:30905761 PMID:31113851 PMID:31353801 PMID:31471524

    Open questions at the time
    • Whether GSDMD and CASP4 activation uses the latent activation domain or a distinct mechanism not resolved
    • Direct binding to CASP4 promoter not confirmed by ChIP
    • Quantitative contribution of IRF2 loss to immune evasion in patients not established
  14. 2020 High

    Tissue-specific conditional deletion showed that IRF2 maintains colonic stem cell self-renewal by limiting IFN signaling, with its loss causing premature differentiation and impaired epithelial regeneration after colitis, extending IRF2's IFN-attenuating role to epithelial homeostasis.

    Evidence Irf2ΔIEC conditional KO mice with organoid assays, flow cytometry, poly(I:C) and DSS colitis models

    PMID:32901054

    Open questions at the time
    • Direct IRF2 target genes in colonic stem cells not identified
    • Whether type I vs. type III IFN is the dominant signal restrained by IRF2 in gut epithelium not distinguished
  15. 2022 High

    Cell-type-specific deletion of IRF2 in CD8+ T cells prevented acquisition of the exhaustion transcriptional program in tumors and sustained effector function, establishing that IFN-driven IRF2 expression is a critical checkpoint linking chronic IFN signaling to T cell dysfunction.

    Evidence CD8+ T cell-specific IRF2 conditional KO, adoptive transfer into tumor-bearing mice, transcriptional profiling, checkpoint blockade experiments

    PMID:36370712

    Open questions at the time
    • Direct transcriptional targets of IRF2 that execute the exhaustion program in CD8+ T cells not catalogued
    • Whether IRF2 acts alone or requires co-factors (e.g. TOX, NFAT) for exhaustion programming unknown
  16. 2023 Medium

    Placement of IRF2 downstream of NOTCH2 signaling in the Ly6Chi-to-Ly6Clo nonclassical monocyte transition resolved the signaling hierarchy controlling this differentiation step and established IRF2 as the required transcription factor independently of NUR77 and BCL6.

    Evidence IRF2 KO mice, myeloid progenitor-specific deletions, in vitro DLL1-induced transition assay with flow cytometry

    PMID:37607223

    Open questions at the time
    • Direct IRF2 target genes that execute the nonclassical monocyte program not identified
    • Whether NOTCH2 directly induces IRF2 expression or acts through intermediaries not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the identity of the full genome-wide IRF2 target repertoire in specific cell types, the structural basis for context-dependent switching between repressor and activator modes, the interplay among phosphorylation/SUMOylation/ubiquitination in regulating IRF2 function in vivo, and the therapeutic potential of modulating IRF2 to reverse CD8+ T cell exhaustion in cancer immunotherapy.
  • No full-length IRF2 structure in complex with corepressors or coactivators
  • In vivo phosphosite-specific mutant phenotypes not characterized
  • Pharmacological tools to modulate IRF2 activity do not exist

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2
Partners
BLIMP1HCFC2IRF1MDM2PIASYRELA

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 IRF-2 was identified as a transcription factor that binds to the same regulatory cis-elements as IRF-1 within IFN and IFN-inducible gene promoters, but functions as a transcriptional repressor rather than an activator, suppressing IRF-1 function by competing for the same binding sequences. cDNA cloning, DNA binding assays, transcriptional reporter assays, competition experiments Cell High 2475256
1993 The DNA recognition sequences of IRF-1 and IRF-2 are virtually indistinguishable; both factors bind the same consensus sequences within IFN and IFN-inducible gene promoters with similar affinities, as determined by PCR-assisted DNA-binding site selection. PCR-assisted DNA binding site selection, EMSA Molecular and cellular biology High 7687740
1993 Targeted disruption of IRF-2 in mice results in up-regulated type I IFN induction following NDV infection, demonstrating that IRF-2 functions as a negative regulator of IFN gene transcription in vivo. IRF-2 knockout mice also exhibit bone marrow suppression of hematopoiesis and B lymphopoiesis. Gene targeting in embryonic stem cells, knockout mice, viral infection assays Cell High 8402903
1994 IRF-2 possesses a transcriptional repression domain in its carboxyl-terminal region and a latent activation domain in its central region. Repression by IRF-2 involves both competition with IRF-1 for promoter binding and silencing of nearby activators via a LexA fusion approach. Deletion mapping, LexA fusion transcriptional assays, reporter gene assays Oncogene High 8152803
1994 The human IRF-2 gene is located at chromosome 4q35.1. The IRF-2 promoter contains an IRF binding site, and IRF-2 gene expression is regulated by IRF-1, establishing a gene network for autoregulation of the IFN system. FISH chromosomal mapping, promoter analysis, transient and stable transfection Molecular and cellular biology Medium 7507207
1995 IRF-2 (identified as histone nuclear factor M, HiNF-M) was purified and shown to be a 48 kDa protein that binds the cell cycle element (CCE) in the human histone H4 gene promoter and activates its transcription, linking IRF-2 to cell cycle-regulated gene expression at the G1/S transition. Protein purification, EMSA, transcriptional reporter assays, recombinant protein binding Nature High 7566094
1995 The oncogenic activity of IRF-2 maps to its N-terminal DNA binding/transcriptional repression domain (first 160 amino acids). Overexpression of wild-type or truncated IRF-2 transforms NIH3T3 cells in vitro and promotes tumor formation in vivo. C-terminal deletion mutagenesis, NIH3T3 transformation assay, soft agar colony assay, nude mouse tumor formation Oncogene High 7630638
1997 IRF-2 is phosphorylated in vivo on serine residues. In vitro, recombinant IRF-2 is a substrate for PKA, PKC, and CK2, but not for JNK1, p38, or ERK2, indicating selective kinase regulation of IRF-2. In vivo 32P labeling with immunoprecipitation, in vitro kinase assays, 2D phosphopeptide mapping, phosphoamino acid analysis Journal of cellular biochemistry High 9213219
1998 Cell cycle regulation of histone H4 gene transcription requires IRF-2. IRF-2-null embryonic fibroblasts lose stringent cell cycle control of histone H4 expression, and reintroduction of IRF-2 restores both mRNA levels and cell cycle-regulated transcription. IRF-2 knockout fibroblasts, synchronized cell culture, mRNA analysis, complementation with IRF-2 re-expression The Journal of biological chemistry High 9417064
1998 The solution structure of the IRF-2 DNA-binding domain (DBD) was determined by NMR spectroscopy. The DBD adopts a winged helix-turn-helix (wHTH) fold with a four-stranded antiparallel beta sheet and three alpha helices. A long loop (Pro37-Asp51) and the second helix of the HTH motif participate in DNA recognition. NMR spectroscopy, DNA binding experiments Structure High 9562558
1999 IRF-2 acts as a transcriptional repressor of the 2-5A synthetase and p21 gene promoters by direct binding to promoter IRF elements, counterbalancing IRF-1 activation. IRF-1 also induces IRF-2 expression via an IRF-E element in the IRF-2 promoter, establishing an autoinhibitory feedback loop. Ectopic expression, EMSA, cotransfection reporter assays, antisense approach Oncogene Medium 10321737
2000 IRF-2 negatively regulates IFN-alpha/beta-induced gene transcription; CD8+ T cell abnormalities and inflammatory skin disease in IRF-2-deficient mice are suppressed by nullizygosity for genes that positively regulate IFN-alpha/beta signaling, placing IRF-2 as a negative regulator of IFN-alpha/beta signaling in vivo. IRF-2 KO mice, genetic epistasis (double KO with IFN-alpha/beta pathway genes), in vitro T cell assays Immunity High 11114377
2000 IRF-2 deficiency in macrophages results in increased basal and IFN-gamma-inducible COX-2 mRNA and protein expression, and two IFN stimulation response elements in the COX-2 promoter bind endogenous IRF-2 to repress transcription. IRF-2 KO macrophages, reporter gene assays, EMSA with endogenous protein, COX-2 protein and PGE2 measurement The Journal of experimental medicine High 10859338
2002 IFN-gamma-induced IRF-1 and IRF-2 bind to three distinct sites in the IL-4 promoter and function as transcriptional repressors, providing a direct mechanism by which IFN-gamma suppresses Th2 cytokine IL-4 expression. Promoter reporter assays, EMSA, chromatin-IP-like binding studies, CD4+ T cell assays Immunity Medium 12479817
2003 IRF-2 co-occupies the IRF-E of the CIITA type IV promoter with IRF-1, stabilizing IRF-1 binding and cooperating to activate CIITA transcription. The IRF-2 DNA binding domain is sufficient for cooperative activation with IRF-1, while a latent activation domain in IRF-2 is required for IRF-2 transactivation of this promoter. EMSA, off-rate experiments, deletion analysis, cotransfection reporter assays Molecular immunology Medium 12493643
2004 Blimp-1, IRF-1, and IRF-2 share similar binding affinities for regulatory sites containing the GAAAG sequence and can compete for the same binding sites in vitro and in vivo, including the IFN-beta promoter, as shown by chromatin immunoprecipitation. Binding competition assays, equilibrium dissociation constant measurement, chromatin immunoprecipitation, cotransfection assays Journal of immunology High 15494505
2008 IRF-2 regulates NF-kappaB activity by physically interacting with RelA/p65 and promoting its nuclear localization. The N-terminal domain of IRF-2 is required for this interaction; knockdown of IRF-2 attenuates TNFalpha-induced NF-kappaB transcription by inhibiting RelA nuclear translocation. Co-immunoprecipitation, subcellular localization assays, siRNA knockdown, NF-kappaB reporter assays, dominant-negative deletion Biochemical and biophysical research communications Medium 18395009
2008 IRF2 is sumoylated in vivo through interaction with the SUMO-E3 ligase PIASy at three sumoylation sites. Sumoylation of IRF2 does not affect nuclear localization or DNA binding but increases its ability to inhibit IRF1 transcriptional activity and decreases its ability to activate ISRE- and H4-driven promoters. Co-IP with PIASy, in vivo sumoylation assay, mutagenesis of sumoylation sites, reporter gene assays, subcellular localization, DNA binding assays Biochemical and biophysical research communications Medium 18514056
2008 IRF2 is a substrate of Mdm2 E3-ubiquitin ligase. Mdm2-mediated ubiquitination of IRF2 requires interaction at both the hydrophobic pocket and the acid domain of Mdm2, mirroring the dual-site mechanism used for p53. IRF2-Mdm2 complex formation occurs in cells. Bioinformatics, in vitro ubiquitination assay, mutagenesis of Mdm2-binding sites on IRF2, co-immunoprecipitation in cells The Biochemical journal High 19032150
2008 IRF2 maintains normal erythropoiesis by attenuating type I IFN signaling. Additional homozygous deletion of IFNAR1 in Irf2-deficient mice rescues the erythropoiesis defect, establishing IRF2 as a regulator of homeostatic erythropoiesis through negative regulation of type I IFN signaling in erythroid cells. IRF-2 KO mice, double KO epistasis (Irf2-/-; Ifnar1-/-), flow cytometry of erythroid progenitors, Bcl-XL expression analysis Experimental hematology High 18207304
2008 IRF2-binding protein-1 (IRF2-BP1), a transcriptional corepressor of IRF2 containing a RING-finger domain, acts as an E3 ubiquitin ligase for JDP2 and represses ATF2-mediated transcription from CRE-containing promoters. Epitope-tag pulldown to identify IRF2-BP1 as JDP2-binding protein, ubiquitination assay, reporter gene assays FEBS letters Medium 18671972
2011 IRF2 directly binds to an interferon-stimulated response element (ISRE) in the MHV68 M2 gene promoter during latency in vivo and functions as an IFNalphabeta-induced transcriptional repressor of M2, limiting viral reactivation from latency. Virus lacking the M2 ISRE shows IRF2-dependent dysregulated M2 expression and uncontrolled reactivation. ChIP in vivo, ISRE mutant virus (ISREΔ), IRF2 knockout mice, viral load and reactivation assays PLoS pathogens High 22114555
2015 IRF2 (not IRF1) is constitutively associated with the TLR3 promoter in unstimulated cells and maintains an open chromatin structure with active histone marks (H3K9/K14 acetylation, H3K4 tri-methylation), while IRF1 binding is induced upon IFN stimulation to drive transcriptional activation. Both IRF1 and IRF2 interact with the BAF chromatin remodeling complex. ChIP assays, histone modification analysis, BAF complex interaction assays, IRF1/IRF2 KO cells, gene expression analysis Cell & bioscience Medium 25960866
2017 IRF2 regulates basal expression of FAM111A; depletion of IRF2 reduces FAM111A expression, and this is the mechanism by which IRF2 knockdown enhances replication of an SPI-1 deletion orthopoxvirus mutant in human cells. Microarray analysis, qRT-PCR, and immunoblotting confirmed IRF2 as a transcriptional regulator of FAM111A. Genome-wide siRNA screen, secondary screen confirmation, microarray analysis, qRT-PCR, immunoblotting Proceedings of the National Academy of Sciences of the United States of America Medium 28320935
2019 IRF2 directly binds to a unique site within the GSDMD promoter to drive GSDMD transcription. Loss of IRF2 substantially attenuates GSDMD expression in macrophages and multiple tissues, reducing IL-1beta secretion and inhibiting pyroptosis by both canonical and non-canonical inflammasomes. Disruption of the single IRF2-binding site in the GSDMD promoter abolishes inflammasome signaling. ENU forward genetic screen, IRF2 KO macrophages and tissues, ChIP/promoter binding, site-directed mutagenesis of GSDMD promoter, pyroptosis and IL-1beta secretion assays Science signaling High 31113851
2019 A genome-wide CRISPR screen identified IRF2 as essential for caspase-4 expression in human monocytes, establishing IRF2 as a transcriptional activator of CASP4 and thereby a regulator of non-canonical inflammasome-driven pyroptosis following cytosolic LPS delivery. IFN-gamma priming can induce IRF1 to compensate for IRF2 deficiency. Genome-wide CRISPR/Cas9 screen, IRF2 KO human monocytes and iPSC-derived monocytes, caspase-4 expression analysis, pyroptosis assays, bacterial infection EMBO reports High 31353801
2019 IRF2 identified in a CRISPR-based forward genetic screen as a transcriptional activator of multiple MHC-I pathway components (immunoproteasomes, TAP, ERAP1) and a transcriptional repressor of PD-L1. Loss of IRF2 impairs cytosol-to-ER peptide transport and N-terminal peptide trimming, reducing antigen presentation. CRISPR forward genetic screen in HeLa cells, IRF2 KO, antigen presentation assays, PD-L1 expression measurement Journal of immunology High 31471524
2019 KRAS* (oncogenic KRAS) represses IRF2 expression, and IRF2 in turn directly represses CXCL3 expression. KRAS*-mediated loss of IRF2 leads to elevated CXCL3, which promotes MDSC migration to the tumor microenvironment via CXCR2, mediating immune suppression and anti-PD-1 resistance. Enforced IRF2 expression in CRC models, CXCL3 reporter assays, CXCR2 inhibition, anti-PD-1 treatment experiments Cancer cell High 30905761
2020 IRF-2 overexpression down-regulates IFN-gamma-induced PD-L1 promoter activity and protein levels in hepatocellular carcinoma cells. Two IRF-1 response elements (IRE1 and IRE2) in the PD-L1 (CD274) promoter were identified, and site-directed mutagenesis confirmed both are functional. IRF-2 antagonizes IRF-1 for binding to the IRE promoter element in PD-L1. IRF-2 overexpression, PD-L1 promoter reporter assays, site-directed mutagenesis, protein expression analysis Cancer immunology, immunotherapy Medium 32377817
2020 IRF2 maintains stemness of colonic stem cells by limiting IFN signaling. Conditional intestinal epithelial deletion of Irf2 (Irf2ΔIEC mice) reduces colonic stem cell numbers and organoid-forming potential, with premature differentiation into transit-amplifying cells, and impairs colon epithelium regeneration after colitis. Conditional KO mice (Irf2ΔIEC), organoid assay, flow cytometry, poly(I:C) injection model, DSS colitis model Scientific reports High 32901054
2021 IRF2 directly binds to the GSDMD promoter (confirmed by ChIP and dual-luciferase reporter assay) to drive GSDMD transcription and promote pyroptosis in cardiomyocytes during myocardial infarction. IRF2 expression in this context may be regulated by HIF-1 signaling. ChIP, dual-luciferase reporter assay, IRF2 silencing in hypoxia model, MI mouse model Molecular medicine reports Medium 34878155
2021 IRF2 transcriptionally activates CENP-N expression by binding its promoter (confirmed by ChIP and dual luciferase reporter assays). CENP-N in turn forms a complex with AKT (confirmed by co-IP and GST pulldown) to regulate glucose metabolism, proliferation, and apoptosis in nasopharyngeal carcinoma cells. ChIP, dual luciferase reporter assay, co-IP, GST pulldown, siRNA knockdown, overexpression Journal of experimental & clinical cancer research Medium 34893086
2022 IRF2 expression in CD8+ T cells is driven by sustained IFN signaling within tumors. CD8+ T cell-specific deletion of IRF2 prevents acquisition of the T cell exhaustion transcriptional program and instead enables sustained effector functions, promoting long-term tumor control. The tumor control by IRF2-deficient CD8+ T cells requires integration of both type I and type II IFN signals. CD8+ T cell-specific IRF2 KO, adoptive transfer, tumor models, transcriptional profiling, checkpoint blockade and adoptive cell therapy experiments Immunity High 36370712
2017 HCFC2 promotes the binding of IRF2 (and IRF1) to the Tlr3 promoter; without HCFC2, IRF2 cannot effectively bind the Tlr3 promoter, and a large subset of IRF2-dependent interferon-regulated genes fails to be transcribed properly. HCFC2 mutations were identified by ENU mutagenesis and confirmed to compromise poly(I:C) responses and viral survival. ENU mutagenesis screen, ChIP for IRF1/IRF2 binding at Tlr3 promoter, macrophage functional assays, viral survival assays The Journal of experimental medicine High 28970238
2023 IRF2 is required cell-intrinsically for the development of Ly6Clo nonclassical monocytes. DLL1-induced NOTCH2 signaling can drive Ly6Chi to Ly6Clo monocyte transition in vitro, and this transition requires IRF2 but can occur in the absence of NUR77 or BCL6, placing IRF2 downstream of NOTCH2 in a transcriptional hierarchy for nonclassical monocyte development. IRF2 KO mice, myeloid progenitor-specific deletions, in vitro DLL1-induced transition assay, flow cytometry Proceedings of the National Academy of Sciences of the United States of America Medium 37607223

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell 901 2475256
1993 Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell 584 8402903
2019 KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer. Cancer cell 507 30905761
1993 Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system. Molecular and cellular biology 404 7687740
1990 Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell 356 2208287
1994 Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system. Molecular and cellular biology 271 7507207
2000 CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling. Immunity 207 11114377
1995 Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2. Nature 171 7566094
2019 IRF2 transcriptionally induces GSDMD expression for pyroptosis. Science signaling 150 31113851
2002 IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Immunity 139 12479817
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. The Journal of experimental medicine 136 10934221
2014 Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3. Cancer research 107 24607843
2000 Interferon regulatory factor (IRF)-1 and IRF-2 regulate interferon gamma-dependent cyclooxygenase 2 expression. The Journal of experimental medicine 107 10859338
2017 MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer. Cell death & disease 104 28471447
2004 B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites. Journal of immunology (Baltimore, Md. : 1950) 102 15494505
1999 IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. Journal of immunology (Baltimore, Md. : 1950) 97 10415056
2022 The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity. Immunity 93 36370712
1994 The oncogenic transcription factor IRF-2 possesses a transcriptional repression and a latent activation domain. Oncogene 87 8152803
2020 Interferon regulatory factor 1 (IRF-1) and IRF-2 regulate PD-L1 expression in hepatocellular carcinoma (HCC) cells. Cancer immunology, immunotherapy : CII 86 32377817
2003 Cloning and expression analysis of rainbow trout Oncorhynchus mykiss interferon regulatory factor 1 and 2 (IRF-1 and IRF-2). Developmental and comparative immunology 86 12543125
2007 Involvement of IFN regulatory factor (IRF)-1 and IRF-2 in the formation and progression of human esophageal cancers. Cancer research 85 17363571
2005 Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance. Blood 85 15914553
2019 Frequent Loss of IRF2 in Cancers Leads to Immune Evasion through Decreased MHC Class I Antigen Presentation and Increased PD-L1 Expression. Journal of immunology (Baltimore, Md. : 1950) 78 31471524
2019 A genome-wide screen identifies IRF2 as a key regulator of caspase-4 in human cells. EMBO reports 77 31353801
1998 Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2. The Journal of biological chemistry 77 9417064
1997 Constitutive activation of Epstein-Barr virus (EBV) nuclear antigen 1 gene transcription by IRF1 and IRF2 during restricted EBV latency. Molecular and cellular biology 65 9001242
1995 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. Infection and immunity 65 7822029
2020 Exosomes derived from human bone marrow mesenchymal stem cells transfer miR-222-3p to suppress acute myeloid leukemia cell proliferation by targeting IRF2/INPP4B. Molecular and cellular probes 63 31968218
1999 Activation and repression of the 2-5A synthetase and p21 gene promoters by IRF-1 and IRF-2. Oncogene 59 10321737
2021 The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis. Journal of experimental & clinical cancer research : CR 56 34893086
2007 Pig conceptuses increase uterine interferon-regulatory factor 1 (IRF1), but restrict expression to stroma through estrogen-induced IRF2 in luminal epithelium. Biology of reproduction 56 17475929
1995 Transcription factor IRF-2 exerts its oncogenic phenotype through the DNA binding/transcription repression domain. Oncogene 53 7630638
2008 Gene structures and promoter characteristics of interferon regulatory factor 1 (IRF-1), IRF-2 and IRF-7 from snakehead Channa argus. Molecular immunology 47 18291530
2016 MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients. Journal of gastroenterology and hepatology 46 26173586
2005 Interferon regulatory factor 1 (IRF-1) and IRF-2 expression in breast cancer tissue microarrays. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 44 16241857
2006 Transcriptional regulation of lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) expression in murine macrophages: role of interferon regulatory factors 1 (IRF-1) and 2 (IRF-2). Journal of endotoxin research 42 17059692
2022 Characterisation of the Circulating Transcriptomic Landscape in Inflammatory Bowel Disease Provides Evidence for Dysregulation of Multiple Transcription Factors Including NFE2, SPI1, CEBPB, and IRF2. Journal of Crohn's & colitis 41 35212366
2014 Ctenopharyngodon idella IRF2 plays an antagonistic role to IRF1 in transcriptional regulation of IFN and ISG genes. Developmental and comparative immunology 38 25463511
2018 miR-18a-5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2. Oncology letters 37 30127908
2015 Division of labor between IRF1 and IRF2 in regulating different stages of transcriptional activation in cellular antiviral activities. Cell & bioscience 37 25960866
2011 A gammaherpesvirus cooperates with interferon-alpha/beta-induced IRF2 to halt viral replication, control reactivation, and minimize host lethality. PLoS pathogens 37 22114555
2021 IRF2 regulates cellular survival and Lenvatinib-sensitivity of hepatocellular carcinoma (HCC) through regulating β-catenin. Translational oncology 36 33735820
2009 Role of Mdm2 acid domain interactions in recognition and ubiquitination of the transcription factor IRF-2. The Biochemical journal 35 19032150
2008 IRF-2 regulates NF-kappaB activity by modulating the subcellular localization of NF-kappaB. Biochemical and biophysical research communications 33 18395009
2017 Triad of human cellular proteins, IRF2, FAM111A, and RFC3, restrict replication of orthopoxvirus SPI-1 host-range mutants. Proceedings of the National Academy of Sciences of the United States of America 32 28320935
2017 Hsa-miR-513b-5p suppresses cell proliferation and promotes P53 expression by targeting IRF2 in testicular embryonal carcinoma cells. Gene 31 28512062
2001 Mutation and association analysis of the interferon regulatory factor 2 gene (IRF2) with atopic dermatitis. Journal of human genetics 31 11721886
1998 The integrated activities of IRF-2 (HiNF-M), CDP/cut (HiNF-D) and H4TF-2 (HiNF-P) regulate transcription of a cell cycle controlled human histone H4 gene: mechanistic differences between distinct H4 genes. Molecular biology reports 30 9540062
2006 Gene structure and transcription of IRF-2 in the mandarin fish Siniperca chuatsi with the finding of alternative transcripts and microsatellite in the coding region. Immunogenetics 29 16871414
2011 Molecular cloning and characterization of interferon regulatory factor 1 (IRF-1), IRF-2 and IRF-5 in the chondrostean paddlefish Polyodon spathula and their phylogenetic importance in the Osteichthyes. Developmental and comparative immunology 28 21703300
2011 IRF-2 is over-expressed in pancreatic cancer and promotes the growth of pancreatic cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 28 22119988
2008 Regulation of IRF2 transcriptional activity by its sumoylation. Biochemical and biophysical research communications 28 18514056
2004 Evaluation of the IRF-2 gene as a candidate for PSORS3. The Journal of investigative dermatology 28 14962090
2009 Intratumoral interferon regulatory factor (IRF)-1 but not IRF-2 is of relevance in predicting patient outcome in ovarian cancer. International journal of cancer 27 19170204
2021 LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2. Diagnostic pathology 25 34022918
2021 IRF2 contributes to myocardial infarction via regulation of GSDMD induced pyroptosis. Molecular medicine reports 25 34878155
2020 LncRNA LINC00265/miR-485-5p/IRF2-mediated autophagy suppresses apoptosis in acute myeloid leukemia cells. American journal of translational research 25 32655783
2003 Psoriatic lesional skin exhibits an aberrant expression pattern of interferon regulatory factor-2 (IRF-2). The Journal of pathology 25 12474233
2020 Circular RNA hsa_circ_0000658 inhibits osteosarcoma cell proliferation and migration via the miR-1227/IRF2 axis. Journal of cellular and molecular medicine 24 33264494
2019 IRF2-INPP4B-mediated autophagy suppresses apoptosis in acute myeloid leukemia cells. Biological research 24 30876449
2017 miR-302b inhibits cancer-related inflammation by targeting ERBB4, IRF2 and CXCR4 in esophageal cancer. Oncotarget 24 28467773
2016 Expression and functional characterization of interferon regulatory factors (irf2, irf7 and irf9) in the blunt snout bream (Megalobrama amblycephala). Developmental and comparative immunology 24 27677680
2013 Molecular characterization of interferon regulatory factor 2 (IRF-2) homolog in pearl oyster Pinctada fucata. Fish & shellfish immunology 24 23422814
2008 Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling. Experimental hematology 23 18207304
2003 The IRF-2 DNA binding domain facilitates the activation of the class II transactivator (CIITA) type IV promoter by IRF-1. Molecular immunology 23 12493643
1998 Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family. Structure (London, England : 1993) 23 9562558
2015 Genetic association of key Th1/Th2 pathway candidate genes, IRF2, IL6, IFNGR2, STAT4 and IL4RA, with atopic asthma in the Indian population. Journal of human genetics 22 25994869
2006 The role of IRF1 and IRF2 transcription factors in leukaemogenesis. Current gene therapy 22 17073600
1993 Characterization of the DNA binding domain of the mouse IRF-2 protein. Protein engineering 22 8475044
2021 IRF2-mediated upregulation of lncRNA HHAS1 facilitates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells by acting as a competing endogenous RNA. Clinical and translational medicine 20 34185419
2017 HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections. The Journal of experimental medicine 20 28970238
2010 Interferon regulatory factor (IRF)-2 activates the HPV-16 E6-E7 promoter in keratinocytes. Virology 20 20129639
2008 IRF2-binding protein-1 is a JDP2 ubiquitin ligase and an inhibitor of ATF2-dependent transcription. FEBS letters 20 18671972
2001 Alterations in IRF1/IRF2 expression in acute myelogenous leukemia. American journal of hematology 20 11559933
1997 Phosphorylation of the oncogenic transcription factor interferon regulatory factor 2 (IRF2) in vitro and in vivo. Journal of cellular biochemistry 20 9213219
2021 Downregulation of IRF2 Alleviates Sepsis-Related Acute Kidney Injury in vitro and in vivo. Drug design, development and therapy 19 34992348
2019 IRF2 is a master regulator of human keratinocyte stem cell fate. Nature communications 19 31611556
2018 [ARTICLE WITHDRAWN] MicroRNA-18a Targets IRF2 and CBX7 to Promote Cell Proliferation in Hepatocellular Carcinoma. Oncology research 19 29386090
2019 LncRNA XIST, as a ceRNA of miR-204, aggravates lipopolysaccharide-induced acute respiratory distress syndrome in mice by upregulating IRF2. International journal of clinical and experimental pathology 18 31934069
2016 MicroRNA-520c enhances cell proliferation, migration, and invasion by suppressing IRF2 in gastric cancer. FEBS open bio 18 28203525
2008 siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth. International journal of oncology 18 18575764
2019 IRF-2 Inhibits Gastric Cancer Invasion and Migration by Down-Regulating MMP-1. Digestive diseases and sciences 17 31350707
2019 IRF1 and IRF2 regulate the non-canonical inflammasome. EMBO reports 17 31379068
2011 Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription. Proceedings of the National Academy of Sciences of the United States of America 17 22042864
1995 IRF-1 and IRF-2 as regulators of the interferon system and cell growth. Indian journal of biochemistry & biophysics 17 8713742
2021 IRF1 and IRF2 act as positive regulators in antiviral response of large yellow croaker (Larimichthys crocea) by induction of distinct subgroups of type I IFNs. Developmental and comparative immunology 16 33444646
2018 Regulation of IL-17 by lncRNA of IRF-2 in the pearl oyster. Fish & shellfish immunology 16 30017925
2015 Fish IRF3 up-regulates the transcriptional level of IRF1, IRF2, IRF3 and IRF7 in CIK cells. Fish & shellfish immunology 16 26545324
2013 Up-regulation of intestinal epithelial cell derived IL-7 expression by keratinocyte growth factor through STAT1/IRF-1, IRF-2 pathway. PloS one 16 23554911
2005 A retroviral library genetic screen identifies IRF-2 as an inhibitor of N-ras-induced growth suppression in leukemic cells. Oncogene 16 16007130
2020 IRF2 maintains the stemness of colonic stem cells by limiting physiological stress from interferon. Scientific reports 15 32901054
2017 IRF2-INPP4B axis participates in the development of acute myeloid leukemia by regulating cell growth and survival. Gene 15 28579269
2002 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. Journal of endotoxin research 15 12537697
2021 Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis. Journal of immunology research 13 34423051
2021 IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3. Virology journal 13 34930359
2012 IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms. International immunology 13 22773153
2009 SUMOylated IRF-1 shows oncogenic potential by mimicking IRF-2. Biochemical and biophysical research communications 13 19962964
2000 The interferon-alpha regulation of interferon regulatory factor 1 (IRF-1) and IRF-2 has therapeutic implications in carcinoid tumors. Annals of oncology : official journal of the European Society for Medical Oncology 13 10942060
2023 Bcl6, Irf2, and Notch2 promote nonclassical monocyte development. Proceedings of the National Academy of Sciences of the United States of America 12 37607223
2022 IRF2 Cooperates with Phosphoprotein of Spring Viremia of Carp Virus to Suppress Antiviral Response in Zebrafish. Journal of virology 12 36314827