Affinage

IRF2

Interferon regulatory factor 2 · UniProt P14316

Length
349 aa
Mass
39.4 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRF2 is a winged helix-turn-helix transcription factor that binds AAGTGA hexamer repeats in interferon (IFN) and IFN-inducible gene promoters, where its founding role is to antagonize the activator IRF-1 at shared cis-elements both by competitive occupancy and by active silencing through a C-terminal repression domain (PMID:2475256, PMID:7687740, PMID:8152803, PMID:9562558). As an in vivo negative regulator of type I IFN gene induction, IRF2 restrains IFN-alpha/beta-driven transcription to preserve tissue homeostasis: its loss causes hematopoietic and B-lymphopoietic suppression, normocytic anemia, CD8+ T cell hyper-responsiveness and inflammatory skin disease, and depletion of colonic and keratinocyte stem cell pools — phenotypes rescued or phenocopied by manipulating IFN signaling (PMID:8402903, PMID:11114377, PMID:18207304, PMID:31611556, PMID:32901054). IRF2 is not merely a passive antagonist: it acts as a direct transcriptional activator of histone H4 genes at the G1/S transition, controlling cell-cycle-regulated gene expression (PMID:7566094, PMID:9417064), and directly drives transcription of the pyroptosis effectors GSDMD and caspase-4 (CASP4), licensing canonical and non-canonical inflammasome signaling and IL-1beta release (PMID:31113851, PMID:31353801, PMID:34878155). It also activates the MHC class I antigen-presentation machinery (immunoproteasome components, TAP, ERAP1) while repressing PD-L1, coupling IRF2 to tumor immune visibility (PMID:31471524, PMID:32377817). IRF2 maintains a primed chromatin state at IFN-inducible promoters such as TLR3 — sustaining basal expression, open chromatin, and active histone marks — through cooperation with the BAF remodeling complex and the cofactor HCFC2 (PMID:25960866, PMID:28970238). In CD8+ T cells, IRF2 converts sustained type I and type II IFN signals into an exhaustion program, and its deletion preserves effector function and antitumor control (PMID:36370712). IRF2 activity is tuned post-translationally by serine phosphorylation (PKA, PKC, CK2), PIASy-mediated sumoylation that enhances repressor and weakens activator function, and Mdm2-dependent ubiquitination requiring dual-site docking (PMID:9213219, PMID:18514056, PMID:19032150).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1989 High

    Established the foundational identity of IRF2: a transcription factor sharing IRF-1's DNA targets but opposing its activity, defining the competitive antagonism model that frames all later work.

    Evidence cDNA cloning with DNA-binding and transcriptional reporter assays

    PMID:2475256

    Open questions at the time
    • Did not define the structural basis of binding or the domain mediating repression
    • Did not address in vivo physiological role
  2. 1993 High

    Resolved whether the antagonism arises from shared DNA recognition by showing IRF-1 and IRF-2 select indistinguishable AAGTGA hexamer repeats, and demonstrated in vivo that IRF-2 normally attenuates type I IFN induction.

    Evidence SELEX/EMSA binding-site selection plus IRF-2 knockout mice with NDV infection and hematopoietic phenotyping

    PMID:7687740 PMID:8402903

    Open questions at the time
    • Did not explain how identical binding produces opposite transcriptional outputs
    • Hematopoietic suppression mechanism not yet tied to IFN signaling
  3. 1994 Medium

    Mapped the molecular basis of repression to a discrete C-terminal repression domain plus a latent central activation domain, and identified an IRF-1-driven autoregulatory loop controlling IRF-2 expression.

    Evidence LexA fusion reporters, truncation analysis, promoter deletion/reporter assays, FISH mapping

    PMID:7507207 PMID:8152803

    Open questions at the time
    • Single-lab domain mapping
    • Identity of silencing partners recruited by the repression domain unknown
  4. 1995 High

    Reframed IRF2 as a bona fide activator, not just an antagonist, by purifying it as the histone H4 cell-cycle-element factor HiNF-M and showing direct activation of H4 transcription, and located its oncogenic activity to the N-terminal DNA-binding/repression domain.

    Evidence Protein purification, EMSA, reconstituted activation assays; deletion mutants with focus formation and nude mouse tumor assays

    PMID:7566094 PMID:7630638

    Open questions at the time
    • How a single domain mediates both repression and transformation not resolved
    • Activator vs repressor context-switch not mechanistically defined
  5. 1997 Medium

    Began defining post-translational control of IRF2 by showing it is phosphorylated on serines by PKA, PKC, and CK2 but not MAP kinases.

    Evidence 32P metabolic labeling, in vitro kinase assays, 2D phosphopeptide and phosphoamino acid analysis

    PMID:9213219

    Open questions at the time
    • Functional consequence of phosphorylation on activity not established
    • Single-lab characterization
  6. 1998 High

    Solidified IRF2 as an active cell-cycle regulator via knockout-plus-rescue showing it is required for cell-cycle-regulated H4 transcription, and defined its fold as a winged helix-turn-helix making the structural basis of hexamer recognition explicit.

    Evidence IRF-2 KO fibroblasts with synchronized cell-cycle analysis and re-expression rescue; NMR structure with DNA-contact mapping

    PMID:9417064 PMID:9562558

    Open questions at the time
    • Structure of full-length protein or DNA co-complex not determined
    • E2F-independent regulatory logic incompletely defined
  7. 2000 High

    Connected IRF2 loss-of-function phenotypes directly to dysregulated IFN-alpha/beta signaling through epistasis, and revealed context-dependent agonist behavior, while extending its repressor reach to the Cox-2 promoter.

    Evidence IRF-2 KO mice with IFNAR nullizygosity rescue; Leishmania infection model and NK/Th1 phenotyping; KO macrophages with EMSA and Cox-2 promoter reporters

    PMID:10859338 PMID:10934221 PMID:11114377

    Open questions at the time
    • Determinants of agonist vs antagonist switching not defined
    • Direct vs indirect targets in immune cells not fully separated
  8. 2002 Medium

    Extended IRF2-mediated repression to T-helper cytokine control, showing IRF-1 and IRF-2 repress the IL-4 promoter downstream of IFN-gamma.

    Evidence EMSA, ChIP, promoter reporters with IRF overexpression in T cells

    PMID:12479817

    Open questions at the time
    • Single-lab evidence
    • Relative contribution of IRF-1 versus IRF-2 not resolved
  9. 2003 Medium

    Defined how the IRF2 DNA-binding domain can cooperate with IRF-1, showing co-occupancy and DBD-sufficient cooperative transactivation at CIITA while autonomous activation requires the latent activation domain.

    Evidence EMSA off-rate, co-occupancy binding, and deletion-mutant reporter assays

    PMID:12493643

    Open questions at the time
    • Promoter features dictating cooperation vs competition unknown
    • Single-lab study
  10. 2004 Medium

    Placed IRF2 within a broader competition network at IFN-beta by showing Blimp-1 shares its GAAAG sites and competes for occupancy.

    Evidence Quantitative binding competition, ChIP, cotransfection reporters

    PMID:15494505

    Open questions at the time
    • Direct IRF-2 vs Blimp-1 displacement not isolated
    • In vivo relevance not tested
  11. 2008 High

    Greatly expanded IRF2 regulation and partnerships: defined PIASy-dependent sumoylation enhancing repression, Mdm2-mediated ubiquitination requiring dual-site docking, physical recruitment of RelA/p65 to the nucleus, and a requirement for IRF2 in erythropoiesis via IFN-signaling attenuation.

    Evidence Co-IP, in vivo sumoylation and site mutagenesis, in vitro ubiquitination with mutagenesis, siRNA with NF-kB reporters/fractionation, KO mice with IFNAR1 double-knockout rescue

    PMID:18207304 PMID:18395009 PMID:18514056 PMID:18671972 PMID:19032150

    Open questions at the time
    • RelA recruitment rests on single Co-IP without reciprocal validation
    • How PTMs are integrated to set activator/repressor balance unresolved
  12. 2015 Medium

    Defined the chromatin-level mechanism of IRF2 priming: it occupies IFN-inducible promoters in the resting state, maintains open chromatin and active histone marks, and physically engages the BAF remodeling complex.

    Evidence ChIP/ChIP-seq for IRF1/IRF2 and histone marks, Co-IP with BAF, IRF2 KO expression analysis

    PMID:25960866

    Open questions at the time
    • BAF interaction not reciprocally validated
    • Single-lab study
  13. 2017 Medium

    Identified a required cofactor (HCFC2) for IRF2 promoter binding at Tlr3 and showed an antiviral phenotype that is indirect, acting through transcriptional control of FAM111A rather than intrinsic IRF2 antiviral activity.

    Evidence ENU and genome-wide siRNA screens with ChIP, replication assays, and expression analysis

    PMID:28320935 PMID:28970238

    Open questions at the time
    • Biochemical nature of the IRF2-HCFC2 interaction not defined
    • Direct vs indirect target distinction relies on a single screen lineage
  14. 2019 High

    Established IRF2 as a direct transcriptional activator of multiple effector programs identified by unbiased screens: GSDMD and CASP4 for pyroptosis, the MHC-I antigen-presentation machinery with PD-L1 repression, and stem-cell/tumor-microenvironment control via keratinocyte fate and the KRAS*-IRF2-CXCL3 axis.

    Evidence ENU and CRISPR forward genetic screens, KO in macrophages/monocytes/HeLa/tumor cells, ChIP and promoter mutagenesis, chromatin/transcriptional profiling, rescue and CXCR2 inhibition

    PMID:30905761 PMID:31113851 PMID:31353801 PMID:31471524 PMID:31611556 PMID:32377817

    Open questions at the time
    • Mechanism selecting activation vs repression at each target promoter not defined
    • Cofactor requirements for direct activation incompletely mapped
  15. 2020 High

    Demonstrated in vivo that IRF2 maintains colonic stem cell stemness specifically by buffering chronic type I IFN signaling, with conditional deletion phenocopied by poly(I:C).

    Evidence Intestinal-epithelium conditional Irf2 KO, organoid assays, DSS colitis, poly(I:C) phenocopy

    PMID:32901054

    Open questions at the time
    • Direct IRF2 target genes in stem cells not enumerated
    • Single-lab study
  16. 2021 Medium

    Broadened IRF2's direct activator repertoire to additional disease-relevant targets, confirming GSDMD-driven cardiomyocyte pyroptosis and identifying CENP-N (in NPC) and INPP4B (in AML) as direct transcriptional targets driving proliferation, glycolysis, autophagy, and apoptosis resistance.

    Evidence ChIP, dual-luciferase reporters, knockdown/overexpression and rescue with phenotypic assays in cardiomyocyte, NPC, and AML models

    PMID:28579269 PMID:34878155 PMID:34893086

    Open questions at the time
    • Each axis validated in a single lab/cell context
    • Tissue-specificity of target selection not explained
  17. 2022 High

    Defined IRF2 as the feedback molecule that converts sustained type I and II IFN signaling into the CD8+ T cell exhaustion program, with cell-intrinsic deletion preserving effector function and antitumor control.

    Evidence CD8+ T cell-specific conditional KO, tumor and adoptive-transfer models, checkpoint therapy, IFN epistasis, transcriptional profiling

    PMID:36370712

    Open questions at the time
    • Direct exhaustion-program target genes bound by IRF2 not fully mapped
    • Translational relevance to human T cells not established
  18. 2023 Medium

    Positioned IRF2 in a developmental transcriptional hierarchy by showing it is required cell-intrinsically downstream of NOTCH2 for nonclassical Ly6Clo monocyte differentiation.

    Evidence Myeloid-progenitor conditional deletion, DLL1-induced transition assay, epistasis with BCL6 and NUR77

    PMID:37607223

    Open questions at the time
    • Direct IRF2 targets in the NOTCH2 pathway unknown
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • What molecular features at a given promoter switch IRF2 between active repressor and direct activator, and how its PTM code (phosphorylation, sumoylation, ubiquitination) integrates with cofactors (BAF, HCFC2) to set this balance, remain unresolved.
  • No unified model linking PTM state to activator/repressor switching
  • No structure of IRF2 in complex with cofactors or at activated vs repressed promoters
  • Determinants of tissue-specific target gene selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 1
Partners
HCFC2IRF1MDM2PIAS4RELASMARCA4

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 IRF2 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 unlike IRF-1, functions as a transcriptional repressor/suppressor of IRF-1-mediated activation, establishing the competitive antagonism model. cDNA cloning, DNA binding assays, transcriptional reporter assays Cell High 2475256
1993 IRF-1 and IRF-2 bind to virtually indistinguishable DNA recognition sequences (AAGTGA hexamer repeats) as determined by PCR-assisted DNA binding site selection; both factors occupy the same cis-elements in IFN-beta and IFN-inducible gene promoters. PCR-assisted DNA binding site selection (SELEX), 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 in fibroblasts, demonstrating that IRF-2 normally attenuates type I IFN gene expression in vivo; IRF-2-deficient mice also exhibit bone marrow suppression of hematopoiesis and B lymphopoiesis. Gene targeting in ES cells (knockout mice), virus infection assays, cellular phenotyping Cell High 8402903
1994 IRF-2 possesses a C-terminal transcriptional repression domain and a latent activation domain in its central region; repression by IRF-2 involves both competition with IRF-1 for promoter binding and active silencing of nearby activators via the repression domain. LexA fusion reporter assays, domain deletion/truncation analysis, transcriptional reporter assays Oncogene Medium 8152803
1994 IRF-2 gene structure is located at chromosome 4q35.1 (human); the IRF-2 promoter contains an IRF binding site, and IRF-1 expression drives IRF-2 transcription, establishing an autoinhibitory regulatory loop within the IFN gene network. FISH chromosomal mapping, promoter deletion/reporter assays, stable and transient transfection Molecular and cellular biology Medium 7507207
1995 IRF-2 (purified as HiNF-M, Mr ~48K) binds the cell-cycle element (CCE) of the human histone H4 gene FO108 and activates H4 transcription, establishing a direct link between IRF-2 and cell-cycle-regulated gene expression at the G1/S transition. Protein purification, EMSA, recombinant protein binding and transcriptional activation assays Nature High 7566094
1995 The oncogenic activity of IRF-2 maps to its N-terminal DNA binding/transcriptional repression domain (first ~160 amino acids), as C-terminal deletions retaining this domain are sufficient for NIH3T3 cell transformation and tumor formation in nude mice. C-terminal deletion mutants, focus formation assay, soft agar anchorage-independent growth, nude mouse tumor formation Oncogene Medium 7630638
1998 Cell-cycle-regulated transcription of histone H4 genes requires IRF-2; IRF-2-null fibroblasts lose stringent cell-cycle control and have reduced H4 mRNA levels, which are restored upon IRF-2 re-introduction, demonstrating that IRF-2 acts as an active transcriptional regulator (not merely a passive IRF-1 antagonist) in E2F-independent cell-cycle gene expression. IRF-2 knockout fibroblasts, synchronized cell cycle analysis, mRNA quantification, rescue by IRF-2 re-expression The Journal of biological chemistry High 9417064
1998 The solution structure of the IRF-2 DNA-binding domain was determined by NMR: it is composed of a four-stranded antiparallel beta-sheet and three alpha-helices forming a winged helix-turn-helix (wHTH) fold; a long loop (Pro37-Asp51) and the second helix of the HTH motif contact the hexamer repeat DNA, defining IRF-2 as a novel subfamily of wHTH proteins. NMR spectroscopy with DNA binding perturbation analysis Structure High 9562558
1997 IRF2 is phosphorylated exclusively on serine residues in vivo; in vitro, PKA, PKC, and CK2 phosphorylate IRF2 at multiple distinct sites, whereas MAP kinases (JNK1, p38, ERK2) do not. 32P metabolic labeling, immunoprecipitation of HA-tagged IRF2, in vitro kinase assays, 2D phosphopeptide mapping, phosphoamino acid analysis Journal of cellular biochemistry Medium 9213219
2000 IRF-2-deficient mice develop an inflammatory skin disease involving CD8+ T cells that exhibit hyper-responsiveness and upregulated IFN-alpha/beta-induced genes; disease and CD8+ T cell abnormality are suppressed by nullizygosity of positive IFN-alpha/beta signaling regulators, establishing IRF-2 as a negative regulator of IFN-alpha/beta-induced transcription necessary for immune homeostasis. IRF-2 knockout mice, CD8+ T cell functional assays, genetic epistasis (IFNAR nullizygosity rescue) Immunity High 11114377
2000 IRF-2 deficiency results in compromised NK cell development (reduced numbers, immature phenotype) and defective Th1 differentiation in vivo; this phenotype cannot be compensated by IRF-1 alone, demonstrating that IRF-2 can act as a functional agonist of IRF-1 for a subset of ISRE-responsive genes. IRF-2 knockout mice, Leishmania major infection model, flow cytometric immune phenotyping The Journal of experimental medicine High 10934221
2000 IRF-2 functions as a negative regulator of the Cox-2 promoter: IRF-2-deficient macrophages show significantly increased basal and IFN-gamma-inducible Cox-2 expression; two IFN stimulation response elements in the mouse Cox-2 promoter bind endogenous IRF-2 and mediate repression. IRF-1/IRF-2 knockout macrophages, Cox-2 mRNA/protein quantification, EMSA, transient transfection reporter assays The Journal of experimental medicine High 10859338
2002 IFN-gamma suppresses IL-4 gene expression through IRF-1 and IRF-2; both factors induced by IFN-gamma bind to three distinct sites in the IL-4 promoter and function as transcriptional repressors of IL-4. EMSA, chromatin immunoprecipitation, promoter reporter assays, IRF-1/IRF-2 overexpression in T cells Immunity Medium 12479817
2003 IRF-2 (DNA binding domain alone) and IRF-1 can co-occupy the IRF-E of the CIITA type IV promoter; the IRF-2 DNA binding domain is sufficient for cooperative transactivation with IRF-1 at this promoter, while the latent activation domain is required for autonomous IRF-2 transactivation. EMSA off-rate assays, deletion mutant reporter assays, co-occupancy DNA binding experiments Molecular immunology Medium 12493643
2004 Blimp-1, IRF-1, and IRF-2 bind with similar affinities to GAAAG-containing regulatory sites; Blimp-1, IRF-1, and IRF-2 all bind the IFN-beta promoter in vivo (by ChIP), and Blimp-1 inhibits IRF-1-dependent activation of IFN-beta promoter in cotransfections, suggesting competition with IRF-2 (and IRF-1) at shared sites. Binding competition assays, equilibrium dissociation constant measurement, ChIP, cotransfection reporter assays Journal of immunology Medium 15494505
2005 IRF-2 autonomously and cell-intrinsically functions as a negative regulator of basophil expansion; IRF-2-deficient mice exhibit STAT6-independent basophil expansion, and reduced basophil numbers (via Kit mutation) abolish spontaneous Th2 polarization, placing IRF-2 upstream of basophil-mediated Th2 control. IRF-2 knockout mice, genetic epistasis with Kit mutation, in vitro Th1/Th2 differentiation assays, basophil depletion/neutralization Blood High 15914553
2008 IRF-2 physically interacts with RelA/p65 and recruits it into the nucleus; IRF-2 knockdown attenuates TNFα-induced NF-κB-dependent transcription by inhibiting nuclear localization of RelA, demonstrating that IRF-2 modulates NF-κB activity by controlling RelA subcellular localization. Co-immunoprecipitation, IRF-2 siRNA knockdown, NF-κB reporter assays, subcellular fractionation Biochemical and biophysical research communications Medium 18395009
2008 IRF2 is sumoylated in vivo at three sites via the SUMO-E3 ligase PIASy; sumoylation does not affect IRF2 nuclear localization or DNA-binding activity, but increases its ability to repress IRF-1-mediated transcription and decreases its ability to activate ISRE and H4 promoters. Co-immunoprecipitation (IRF2/PIASy interaction), mutagenesis of sumoylation sites, in vivo sumoylation assay, reporter assays Biochemical and biophysical research communications Medium 18514056
2008 IRF-2 is a substrate of Mdm2 E3-ubiquitin ligase requiring dual-site interaction: one binding site in IRF-2 contacts the Mdm2 hydrophobic pocket and a second requires the Mdm2 acid domain; mutation of either site attenuates IRF-2 ubiquitination, and the Mdm2/IRF-2 complex forms in cells. Co-immunoprecipitation (Mdm2/IRF-2 complex in cells), in vitro ubiquitination assays, site-directed mutagenesis of IRF-2 binding sites The Biochemical journal High 19032150
2008 IRF2 is required for homeostatic erythropoiesis: IRF2-null mice develop normocytic anemia with decreased late erythroblasts and increased apoptosis; this defect is rescued by additional knockout of IFNAR1, demonstrating that IRF2 maintains erythropoiesis by attenuating type I IFN signaling in erythroid progenitors. IRF-2 knockout mice, flow cytometric erythroid progenitor analysis, genetic epistasis (IFNAR1 double knockout rescue), apoptosis assays Experimental hematology High 18207304
2008 IRF2-binding protein-1 (IRF2-BP1), which co-represses IRF2 transcriptional activity, also functions as a JDP2 ubiquitin E3 ligase via its RING-finger domain, enhancing JDP2 polyubiquitination and repressing ATF2-mediated transcription from CRE-containing promoters. Epitope-tag co-immunoprecipitation, in vitro ubiquitination assay, CRE reporter assays FEBS letters Medium 18671972
2015 IRF2 occupies TLR3 and other IFN-inducible gene promoters in the unstimulated state and maintains basal expression, open chromatin structure, and active histone modifications (H3K9/K14 acetylation, H3K4 trimethylation); IRF2 also directly interacts with the BAF chromatin remodeling complex to maintain this primed state, while IRF1 drives rapid transcriptional activation upon stimulation. ChIP-seq/ChIP assays for IRF1, IRF2, histone marks; Co-immunoprecipitation with BAF complex; gene expression in IRF2 KO cells Cell & bioscience Medium 25960866
2017 IRF2 regulates the basal expression level of FAM111A transcriptionally; in a genome-wide siRNA screen, depletion of IRF2 enhanced replication of SPI-1-deleted orthopoxvirus, and this effect was found to be indirect through FAM111A (and the RFC complex), rather than direct antiviral activity by IRF2. Genome-wide siRNA screen, custom replication assays, microarray, quantitative RT-PCR, immunoblotting Proceedings of the National Academy of Sciences of the United States of America Medium 28320935
2017 HCFC2 is required for binding of both IRF1 and IRF2 to the Tlr3 promoter; HCFC2 mutations abolish macrophage responses to poly(I:C) and impair survival during viral infections, placing HCFC2 as a required co-factor for IRF2-dependent Tlr3 transcription. ENU mutagenesis screen, ChIP for IRF1/IRF2 at Tlr3 promoter, macrophage functional assays, infection survival studies The Journal of experimental medicine Medium 28970238
2019 IRF2 directly binds a unique site in the GSDMD promoter to drive GSDMD transcription; IRF2-deficient macrophages show substantially reduced GSDMD expression, decreased IL-1β secretion, and inhibited pyroptosis; disruption of this single IRF2-binding site abolishes both canonical and non-canonical inflammasome signaling. ENU forward genetic screen, IRF2 KO macrophages, ChIP, promoter reporter assays with site-directed mutagenesis Science signaling High 31113851
2019 IRF2 is identified by CRISPR genome-wide screen as required for caspase-4 expression and cytosolic LPS-mediated pyroptosis in human monocytes; IRF2 directly transcriptionally regulates caspase-4 (CASP4) levels; IFN-γ priming can compensate IRF2 deficiency through IRF1 induction. Genome-wide CRISPR/Cas9 screen, IRF2 KO in human monocytes and iPSC-derived monocytes, CASP4 expression analysis, bacterial infection assays EMBO reports High 31353801
2019 IRF2 loss of function (identified by CRISPR screen) leads to reduced MHC class I antigen presentation by decreasing transcription of immunoproteasome components, TAP, and ERAP1, and simultaneously increases PD-L1 expression; IRF2 thus acts as a transcriptional activator of MHC-I pathway genes and a repressor of PD-L1. CRISPR forward genetic screen, IRF2 KO in HeLa and tumor cells, MHC-I antigen presentation assays, gene expression profiling Journal of immunology High 31471524
2019 KRAS* represses IRF2 expression, which in turn directly represses CXCL3 transcription; KRAS*-mediated loss of IRF2 causes high CXCL3 expression that drives MDSC migration to tumors via CXCR2, promoting immune evasion. Enforced IRF2 expression rescue experiments, CXCR2 inhibition, tumor microenvironment immune cell analysis Cancer cell Medium 30905761
2019 IRF-2 overexpression down-regulates IFN-γ-induced PD-L1 promoter activity and protein levels in HCC cells in a dose-dependent manner; two functional IRF-1 response elements (IRE1 and IRE2) in the PD-L1 (CD274) promoter are bound by both IRF-1 and IRF-2, with IRF-2 antagonizing IRF-1-mediated PD-L1 activation. IRF-2 overexpression, PD-L1 promoter reporter assays, site-directed mutagenesis of IREs, IFN-γ stimulation assays Cancer immunology, immunotherapy : CII Medium 32377817
2019 IRF2 is a master regulator of human keratinocyte stem cell fate: CRISPR knockdown of IRF2 in keratinocytes with low stem cell potential increases self-renewal, migration, and epidermis formation; IRF2 binds and regulates active cis-regulatory elements at interferon response and antigen presentation genes in keratinocytes. Chromatin profiling, transcriptional profiling, CRISPR-KD, keratinocyte functional assays (self-renewal, migration, epidermis formation) Nature communications Medium 31611556
2020 Conditional deletion of Irf2 in intestinal epithelium causes premature differentiation of colonic stem cells (CoSCs) into transit-amplifying cells, reducing CoSC numbers and organoid-forming potential; this phenotype is phenocopied by repeated poly(I:C) injections in wild-type mice, demonstrating that IRF2 maintains colonic stem cell stemness by attenuating chronic type I IFN signaling. Conditional Irf2 knockout mice (Irf2ΔIEC), DSS colitis model, organoid assays, poly(I:C) injection epistasis Scientific reports High 32901054
2021 IRF2 directly binds the GSDMD promoter to drive GSDMD transcription in cardiomyocytes; IRF2 silencing in hypoxia-treated H9c2 cells decreases GSDMD, GSDMD-N, and cleaved caspase-1 levels and reduces IL-1β and IL-18, confirming IRF2 as a transcriptional regulator of pyroptosis in myocardial infarction. Chromatin immunoprecipitation, dual luciferase reporter assay, IRF2 siRNA knockdown in H9c2 cells, in vivo MI model with IRF2 silencing Molecular medicine reports Medium 34878155
2021 IRF2 directly transcriptionally activates CENP-N expression in NPC cells (confirmed by ChIP and dual luciferase assays); the IRF2/CENP-N/AKT axis promotes aerobic glycolysis, proliferation, cell cycling, and apoptosis resistance; CENP-N forms a complex with AKT (confirmed by immunoprecipitation and GST pulldown). ChIP, dual luciferase reporter assay, immunoprecipitation, GST pulldown, CENP-N KD/OE with phenotypic assays Journal of experimental & clinical cancer research : CR Medium 34893086
2021 IRF2 transcriptionally activates INPP4B in AML cells by binding its promoter; IRF2-driven INPP4B expression promotes autophagy and suppresses apoptosis; restoration of INPP4B blocks the pro-apoptotic effects of IRF2 knockdown. IRF2 overexpression/knockdown, INPP4B rescue experiments, autophagy markers (LC3-I/II, Beclin-1, p62), colony formation, apoptosis assays Gene Medium 28579269
2022 CD8+ T cell-specific deletion of IRF2 prevents acquisition of the T cell exhaustion transcriptional program within tumors, enabling sustained effector functions; sustained antitumor control by IRF2-deficient CD8+ T cells requires continuous integration of both type I and type II IFN signals, establishing IRF2 as a feedback molecule that converts IFN signals into T cell suppression. CD8+ T cell-specific IRF2 conditional knockout, tumor models, adoptive cell therapy, immune checkpoint therapy, transcriptional profiling Immunity High 36370712
2023 IRF2 is required cell-intrinsically for development of Ly6Clo (nonclassical) monocytes; NOTCH2/DLL1-induced transition of Ly6Chi to Ly6Clo monocytes requires IRF2, placing IRF2 downstream of NOTCH2 in a transcriptional hierarchy controlling nonclassical monocyte fate. IRF2 conditional deletion in myeloid progenitors, in vitro DLL1-induced monocyte transition assay, genetic epistasis with BCL6 and NUR77 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 903 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 517 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 154 31113851
2002 IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Immunity 140 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 105 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) 103 15494505
2022 The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity. Immunity 100 36370712
1999 IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. Journal of immunology (Baltimore, Md. : 1950) 97 10415056
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) 81 31471524
2019 A genome-wide screen identifies IRF2 as a key regulator of caspase-4 in human cells. EMBO reports 79 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 64 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 58 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
2016 MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients. Journal of gastroenterology and hepatology 47 26173586
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
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
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 42 35212366
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
2015 Division of labor between IRF1 and IRF2 in regulating different stages of transcriptional activation in cellular antiviral activities. Cell & bioscience 39 25960866
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
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
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 29 21703300
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 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 IRF2 contributes to myocardial infarction via regulation of GSDMD induced pyroptosis. Molecular medicine reports 26 34878155
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
2020 LncRNA LINC00265/miR-485-5p/IRF2-mediated autophagy suppresses apoptosis in acute myeloid leukemia cells. American journal of translational research 25 32655783
2013 Molecular characterization of interferon regulatory factor 2 (IRF-2) homolog in pearl oyster Pinctada fucata. Fish & shellfish immunology 25 23422814
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
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 Downregulation of IRF2 Alleviates Sepsis-Related Acute Kidney Injury in vitro and in vivo. Drug design, development and therapy 21 34992348
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
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
2016 MicroRNA-520c enhances cell proliferation, migration, and invasion by suppressing IRF2 in gastric cancer. FEBS open bio 19 28203525
2019 IRF-2 Inhibits Gastric Cancer Invasion and Migration by Down-Regulating MMP-1. Digestive diseases and sciences 18 31350707
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
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 18 22042864
2008 siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth. International journal of oncology 18 18575764
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 17 33444646
2019 IRF1 and IRF2 regulate the non-canonical inflammasome. EMBO reports 17 31379068
1995 IRF-1 and IRF-2 as regulators of the interferon system and cell growth. Indian journal of biochemistry & biophysics 17 8713742
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

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