Affinage

IRF1

Interferon regulatory factor 1 · UniProt P10914

Length
325 aa
Mass
36.5 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRF1 is a stimulus-inducible transcription factor that integrates interferon and inflammatory signaling into programs of antiviral defense, macrophagic immunity, inflammatory cell death, and cell growth control (PMID:36736301, PMID:36384204). It engages target promoters through an N-terminal DNA-binding domain that, together with a C-terminal extension, recognizes ISRE/IRF-E elements, while a separable acidic C-terminal domain provides transcriptional activation and a dedicated NLS directs nuclear import; the same protein carries a heterodimerization surface that mediates binding to ICSBP/IRF2 (PMID:9742224). Through direct promoter binding IRF1 activates antiviral and growth-suppressive genes including PKR, 2-5A synthetase, and the cell-cycle inhibitor p21, and induces IRF2 itself to establish autoinhibitory feedback (PMID:8622878, PMID:10321737), while functioning as a repressor at other loci such as IL-4, PGC1α, and SLC7A11 (PMID:12479817, PMID:32938919, PMID:37441987). At chromatin, IRF1 acts as a pioneering/remodeling factor that opens ISG and lineage-specific loci, recruits BRD4, and maintains H3K4me1 to enable rapid and constitutive induction of interferon-stimulated and pattern-recognition genes including TLR2/TLR3 (PMID:31156620, PMID:33761354, PMID:28166218). Human IRF1 deficiency demonstrates that this factor is essential for IFN-γ-dependent control of mycobacteria and intramacrophagic pathogens but largely redundant for IFN-α/β antiviral responses (PMID:36736301). IRF1 output is gated by tightly controlled protein turnover: GSK3β phosphorylation at T181 creates a phosphodegron recognized by SCF-Fbxw7α, and this ubiquitin-driven degradation of DNA-bound IRF1 is itself required for productive RNA Pol II elongation at target promoters (PMID:30854564), whereas DNA binding occludes the Mf2 docking site used by CHIP and MDM2 to protect active IRF1 (PMID:23134341). Stability is further tuned by XAF1 (antagonizing CHIP), SPOP-mediated ubiquitination, and Roquin-mediated mRNA destabilization (PMID:35972291, PMID:36481790, PMID:31451648). IRF1 also acts within IFN-γ-induced KAT8 condensates, where acetylation at K78 drives CD274/PD-L1 transcription (PMID:36894639), cooperates with partners such as BATF2 and IRF3 (whose activation it promotes by blocking PP2A) (PMID:25957166, PMID:32878885), and directs inflammatory cell-death programs by transactivating GSDMD, CASP1, GBP5, and ZBP1 and contributing to PANoptosome activation (PMID:36384204, PMID:38229660, PMID:39026271, PMID:37557956).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established that IRF1 is not merely an interferon-responsive marker but a functional transcriptional activator of an effector gene, linking it directly to antiviral output.

    Evidence IRF-1 knockout fibroblasts and rescue transfection in haploinsufficient cells measuring PKR levels

    PMID:8622878

    Open questions at the time
    • Did not map the IRF-E in the PKR promoter
    • Did not address other target genes
  2. 1998 High

    Defined the modular architecture of IRF1, separating DNA binding, nuclear import, heterodimerization, and transactivation into discrete domains.

    Evidence GFP-fusion imaging, in vitro heterodimerization, two-hybrid and deletion mutagenesis of murine IRF-1

    PMID:9742224

    Open questions at the time
    • Domain function defined largely in vitro/ectopic systems
    • Structural basis of DNA recognition not resolved
  3. 1999 High

    Showed IRF1 directly binds and transactivates growth-suppressive and antiviral promoters while autoregulating via IRF2, framing it as a bidirectional regulator within a feedback network.

    Evidence EMSA promoter binding plus CAT reporter and antisense assays for 2-5A synthetase, p21, and IRF-2

    PMID:10321737

    Open questions at the time
    • Quantitative contribution of each IRF-E in vivo not established
    • Cell-type specificity of feedback loop unaddressed
  4. 2002 High

    Demonstrated IRF1 can act as a transcriptional repressor, providing a direct mechanism for IFN-γ antagonism of Th2 responses.

    Evidence EMSA, reporter assays, and IRF-1/IRF-2 over/knockdown at the IL-4 promoter in CD4+ T cells

    PMID:12479817

    Open questions at the time
    • Co-repressor machinery not identified
    • Does not explain switch between activation and repression at different promoters
  5. 2002 Medium

    Placed IRF1 activation within an antiviral signaling axis targeted by viral immune evasion.

    Evidence HCV NS5A colocalization with PKR, replicon system, and NS5A mutant reporter assays

    PMID:11904369

    Open questions at the time
    • IRF1 activation inferred from downstream readouts rather than measured directly
    • Single lab, indirect link via PKR
  6. 2013 High

    Resolved how active DNA-bound IRF1 is protected from degradation, coupling its transcriptional state to its stability.

    Evidence In vitro ubiquitination, Mf2 mutagenesis, and DNA-binding competition with CHIP and MDM2

    PMID:23134341

    Open questions at the time
    • In vitro reconstitution only
    • Relative in vivo contribution of CHIP vs MDM2 unclear
  7. 2019 High

    Uncovered a phosphodegron mechanism in which regulated IRF1 turnover is paradoxically required for transcription, linking degradation to Pol II elongation.

    Evidence T181A mutagenesis, ChIP, RNA Pol II elongation assays, and Fbxw7-deficient cells

    PMID:30854564

    Open questions at the time
    • Mechanistic coupling of ubiquitination to elongation not fully defined
    • Generality across all IRF1 targets untested
  8. 2019 High

    Defined IRF1 as a chromatin-priming factor that recruits BRD4 and maintains active histone marks for rapid and constitutive ISG induction.

    Evidence CRISPR KO, transcriptomics, ChIP for BRD4 and H3K4me1, and IFN/JAK-STAT blockade

    PMID:31156620

    Open questions at the time
    • How IRF1 selects ISG loci genome-wide not fully resolved
    • Direct vs indirect H3K4me1 maintenance unclear
  9. 2017 High

    Established IRF1 as a pioneering transcription factor that opens chromatin during lymphoid and myeloid differentiation programs.

    Evidence ATAC-seq and RNA-seq in IRF1- and BATF-deficient cells during IL-27-driven Tr1 differentiation; later extended to macrophage TLR4 responses

    PMID:28166218 PMID:33761354

    Open questions at the time
    • Cofactors enabling nucleosome engagement not defined
    • Lineage selectivity of remodeling mechanism unexplained
  10. 2017 High

    Showed IRF1 promoter occupancy depends on accessory factors, identifying HCFC2 as a determinant of IRF1/IRF2 binding to the Tlr3 promoter.

    Evidence ENU screen, ChIP for IRF1/IRF2, genetic complementation, and poly(I:C) macrophage responses

    PMID:28970238

    Open questions at the time
    • Molecular basis of HCFC2-IRF1 cooperation unresolved
    • Generality to other IRF1 targets untested
  11. 2020 High

    Defined IRF1 as a multi-pathway driver of inflammatory cell death by directly transactivating pyroptotic and apoptotic effector genes.

    Evidence ChIP/reporter assays and IRF1 KO mice for caspase-3, GSDMD, CASP1, and DRP1 across intestinal, vascular, and barrier-injury models

    PMID:32641998 PMID:34309645 PMID:36384204

    Open questions at the time
    • Context determinants selecting cell-death program not defined
    • Direct vs indirect promoter effects vary by study
  12. 2020 High

    Demonstrated IRF1 enhances IRF3 activation by shielding it from PP2A, expanding IRF1 into a post-translational regulator of partner transcription factors.

    Evidence Co-IP, IRF1 DBD deletion mutants, and PP2A interaction competition during viral infection

    PMID:32878885

    Open questions at the time
    • Stoichiometry of the IRF1-IRF3-PP2A interaction unknown
    • Whether this is DNA-independent unclear
  13. 2022 High

    Identified SPOP-mediated and Roquin-mediated negative regulation that constrains IRF1-driven immune and PD-L1 expression.

    Evidence Co-IP and ubiquitination assays with SPOP mutants; CLIP-seq mapping of Roquin binding to IRF1 mRNA

    PMID:31451648 PMID:36481790

    Open questions at the time
    • Degradation site mapping incomplete
    • Interplay with stabilizing factors not reconciled
  14. 2023 High

    Showed IRF1 functions within phase-separated KAT8 condensates where K78 acetylation drives PD-L1 transcription, adding biomolecular condensates and acetylation to IRF1 regulation.

    Evidence Phase separation assays, MS, K78 mutagenesis, ChIP, and in vivo tumor models with a blocking peptide

    PMID:36894639

    Open questions at the time
    • Generality of condensate behavior to non-PD-L1 targets untested
    • Determinants of condensate composition unclear
  15. 2023 High

    Human IRF1 deficiency established the non-redundant, pathway-specific role of IRF1 in IFN-γ-dependent macrophagic immunity versus dispensable IFN-α/β antiviral function.

    Evidence IRF1-deficient patient cells with IFN-γ and IFN-α/β stimulation, mycobacterial killing, and viral infection assays

    PMID:36736301

    Open questions at the time
    • Molecular basis of IFN-type selectivity not fully defined
    • Spectrum of susceptible pathogens incomplete
  16. 2024 Medium

    Revealed NLS-localized PTMs and mtDNA/STING-linked signals controlling IRF1 nuclear translocation and activation.

    Evidence MS PTM mapping, NLS site mutagenesis, nuclear translocation imaging, and SSBP1-IRF1 co-IP in radiation and infection models

    PMID:38849539

    Open questions at the time
    • Enzymes depositing each NLS PTM only partly defined
    • In vivo physiological relevance limited to specific stress models

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IRF1 selects between transcriptional activation and repression, and how its post-translational modifications, condensate behavior, and turnover are integrated to specify divergent cell-fate outcomes (antiviral defense vs PANoptosis vs growth control), remains unresolved.
  • No unified model linking PTM state to activator vs repressor function
  • Determinants of target-gene selection across tissues unknown
  • Structural model of DNA-bound IRF1 with cofactors absent from corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
BATF2ICSBPIRF2IRF3KAT8SPI1SPOPXAF1

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Functional domain mapping of murine IRF-1 identified: (1) a minimal DNA-binding domain requiring N-terminal 124 amino acids plus a C-terminal extension; (2) a nuclear localization signal (NLS) sufficient for nuclear translocation; (3) a heterodimerization domain (homologous to IRF-2) that mediates interaction with ICSBP in vitro; (4) an acidic C-terminal domain required and sufficient for transcriptional activation. GFP-fusion mutant live-cell imaging, in vitro heterodimerization assays, mammalian two-hybrid system, epitope mapping The Biochemical journal High 9742224
2002 IRF-1 and IRF-2 induced by IFN-γ bind to three distinct sites in the IL-4 promoter and function as transcriptional repressors of IL-4 gene expression, providing a direct negative feedback mechanism by which IFN-γ attenuates Th2 responses. Electrophoretic mobility shift assay (EMSA), reporter gene assays, IRF-1/IRF-2 overexpression and knockdown in CD4+ T cells Immunity High 12479817
2002 HCV NS5A protein colocalizes with PKR and suppresses dsRNA-mediated activation of PKR, thereby blocking IRF-1 activation and induction of IRF-1-dependent antiviral genes; mutations in the PKR-binding domain of NS5A relieved this blockade and reduced HCV replication efficiency. Colocalization (subcellular imaging), reporter gene assays with NS5A mutants, HCV subgenomic replicon system, dsRNA stimulation Proceedings of the National Academy of Sciences of the United States of America Medium 11904369
1996 IRF-1 transcriptionally activates PKR expression: IRF-1-deficient mouse embryonic fibroblasts show reduced PKR levels, and transfection of IRF-1 into IRF-1-haploinsufficient U937 cells (which carry a deletion of one IRF-1 allele) is sufficient to induce PKR expression. IRF-1 knockout fibroblasts, transient transfection overexpression, Western blot/Northern blot for PKR levels Oncogene High 8622878
1999 IRF-1 transactivates the 2-5A synthetase and p21 (WAF1/CIP1) gene promoters by directly binding to IRF-binding elements within them; IRF-2 counteracts this activation; and IRF-1 also induces transcription of IRF-2 itself via an IRF-E in the IRF-2 promoter, establishing an autoinhibitory feedback loop. EMSA (direct promoter binding), CAT reporter transfection assays, IRF-1/IRF-2 ectopic expression and antisense constructs Oncogene High 10321737
2014 DTX3L and ARTD9 (PARP9) form a complex that acts as a transcriptional repressor of IRF1 in metastatic prostate cancer cells; co-immunoprecipitation confirmed physical interaction between DTX3L, ARTD8, and ARTD9. Co-immunoprecipitation, Western blot, siRNA knockdown, immunofluorescence Molecular cancer Medium 24886089
2015 BATF2 physically associates with IRF1 (demonstrated by co-immunoprecipitation), and this Batf2/Irf1 complex drives expression of inflammatory genes (Tnf, Ccl5, Nos2, Il12b) in IFN-γ-activated macrophages and during Mycobacterium tuberculosis infection. Co-immunoprecipitation, Irf1 knockdown, gene expression profiling Journal of immunology Medium 25957166
2019 IRF1 enhances recruitment of BRD4 to promoter-enhancer regions of interferon-stimulated genes (ISGs) for rapid transcriptional induction, and maintains histone H3K4me1 levels at ISG loci for constitutive expression; IRF1 also regulates constitutive expression of TLR2 and TLR3, promoting signaling through these pattern recognition receptors. CRISPR KO cell line, transcriptome analysis, chromatin immunoprecipitation (ChIP) for BRD4 and H3K4me1, IFN/JAK-STAT blockade, viral infection assays Frontiers in immunology High 31156620
2019 GSK3β phosphorylates IRF1 at residue T181, generating a phosphodegron recognized by the SCF-Fbxw7α E3 ubiquitin ligase, which ubiquitinates and degrades DNA-bound IRF1; T181A mutation stabilizes IRF1 at target promoters but blocks RNA Pol II elongation and transcription of target genes, abolishing anti-proliferative activity. Site-directed mutagenesis (T181A), ChIP, RNA Pol II elongation assay, proteasome inhibition, Fbxw7-deficient cell lines, proliferation assays Nucleic acids research High 30854564
2013 E3 ligases CHIP and MDM2 dock to the Mf2 domain of IRF-1 and ubiquitinate lysine residues predominantly in loop structures of the DNA-binding domain; when IRF-1 is bound to cognate DNA, the Mf2 docking site is occluded, suppressing ubiquitination and protecting active DNA-bound IRF-1 from degradation. In vitro ubiquitination assays, DNA-binding competition assays, site-directed mutagenesis of Mf2 domain The Biochemical journal High 23134341
2023 In IFN-γ-stimulated cells, KAT8 undergoes phase separation with IRF1, forming biomolecular condensates; within these condensates KAT8 acetylates IRF1 at K78, which promotes IRF1 binding to the CD274 (PD-L1) promoter and enriches the transcription apparatus to drive PD-L1 transcription; a blocking peptide (2142-R8) disrupts KAT8-IRF1 condensate formation and inhibits PD-L1 expression. Phase separation assays, co-immunoprecipitation, mass spectrometry, mutagenesis of IRF1 K78, ChIP, in vitro and in vivo tumor models with blocking peptide Nature cancer High 36894639
2022 SPOP (E3 ubiquitin ligase adaptor) binds IRF1 and triggers its ubiquitin-proteasomal degradation, thereby suppressing IRF1-mediated transcriptional upregulation of PD-L1; cancer-associated SPOP mutants lose the ability to degrade IRF1, resulting in IRF1 stabilization and elevated PD-L1 expression. Co-immunoprecipitation, ubiquitination assay, proteasome inhibition, Western blot with SPOP mutants, reporter assays Cell death and differentiation High 36481790
2020 IRF1 directly binds to the promoter region of DRP1 and suppresses its expression; IS (indoxyl sulfate) upregulates IRF1, which in turn reduces DRP1 and inhibits mitophagic flux, causing intestinal barrier injury; IRF1 knockout mice are protected from these effects. ChIP assay (IRF1 binding to DRP1 promoter), IRF1 knockout mice, DRP1 overexpression rescue, Western blot, transmission electron microscopy Theranostics High 32641998
2020 IRF1 directly binds to the promoter of PGC1α (via histone H3K9 acetylation-dependent upregulation of IRF1 by high phosphate) and transcriptionally represses PGC1α expression, leading to myocardial energy metabolism dysfunction in cardiorenal syndrome type 4. ChIP assay (IRF1 binding to PGC1α promoter), IRF1 knockdown, IRF1 knockout mice, histone acetylation analysis Nature communications High 32938919
2022 IRF-1 is transcriptionally upregulated by RelB/p52 (non-canonical NF-κB) binding to the IRF-1 promoter at −782/−770; IRF-1 in turn binds the GSDMD promoter at −526/−515 and the CASP1 promoter at −11/10 to promote their expression, driving NLRP3 inflammasome-mediated pyroptosis and atherosclerosis. ChIP assay, RNA-seq, endothelial-specific NIK and IRF-1 KO mice on Apoe-null background, luciferase reporter, Western blot Translational research High 36384204
2020 IRF1 is required for caspase-3 expression in intestinal epithelial cells by directly binding to IRF1-binding sites in the caspase-3 promoter, as confirmed by dual-luciferase reporter and ChIP assays; IRF1−/− mice are completely protected from TNFα-induced IEC shedding. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), IRF1 and caspase-3 knockout mice, TNFα-injection model Journal of Crohn's & colitis High 34309645
2020 IRF1 interacts with IRF3 (via its DNA-binding domain) and augments IRF3 activation by blocking the interaction between IRF3 and protein phosphatase 2A (PP2A), thereby increasing IRF3 phosphorylation and innate immune gene induction during viral infection. Co-immunoprecipitation, IRF1 DBD deletion mutants, PP2A interaction competition assay, siRNA knockdown, viral infection assays Journal of virology High 32878885
2018 IRF1 promotes STAT1 phosphorylation at Y701 and JAK1 phosphorylation, enabling STAT1 dimerization and binding to gamma-activated sequence (GAS) elements; the transactivation domain of IRF1 is required for this effect, and IRF1-conditioned medium (containing a secreted factor that is not IFN-β or IFN-γ) can activate STAT1 in recipient cells; loss of IRF1 reduces sustained IFN-γ-induced STAT1 phosphorylation. IRF1 transient overexpression and CRISPR KO in HEK293 cells, GAS-reporter assays, anti-IFN neutralizing antibodies, Western blot for phospho-STAT1/JAK1, EMSA for STAT1-GAS binding Immunology and cell biology Medium 29893425
2000 IRF-1 binds to an ISRE/IRF-E candidate sequence in the SMN and SMNc gene promoters in vitro, and overexpression of IRF-1 induces SMN/SMNc mRNA and protein expression in transfection assays; IFN-β and IFN-γ induction of SMN genes is at least partly mediated by IRF-1. In vitro DNA binding (EMSA), transfection reporter/overexpression assays, primary fibroblasts from SMA patients, Western blot Molecular medicine Medium 11147573
2014 Oncogenic Ras/MEK signaling downregulates IRF1 protein expression; MEK inhibition restores IRF1 expression; and re-expression of IRF1 in human cancer cells renders them resistant to oncolytic vesicular stomatitis virus, placing IRF1 downstream of Ras/MEK in suppressing IFN-inducible gene transcription. Promoter deletion analysis, IRF1−/− MEFs (epistasis), MEK inhibitor treatment, IRF1 re-expression, oncolytic virus infection assays Oncogene High 25347735
2019 XAF1 stabilizes IRF1 protein by antagonizing CHIP-mediated ubiquitination and degradation of IRF1; this XAF1-IRF1 positive feedback loop induces antiviral IRF1 target genes (DDX58, DDX60, MX1, OAS2) and restricts RNA virus replication. Co-immunoprecipitation, XAF1 knockout cell lines, CHIP ubiquitination assay, viral infection in vitro and in vivo mouse models Journal of virology Medium 35972291
2017 HCFC2 promotes the binding of IRF1 and IRF2 to the Tlr3 promoter; without HCFC2, IRF1/IRF2 binding is impaired, resulting in reduced Tlr3 transcription and diminished poly(I:C)-induced cytokine and type I IFN responses in macrophages. ENU mutagenesis screen, ChIP for IRF1/IRF2 at Tlr3 promoter, genetic complementation, macrophage poly(I:C) stimulation, viral infection survival assays The Journal of experimental medicine High 28970238
2019 Human cytomegalovirus induces Roquin expression; Roquin binds IRF1 mRNA directly (identified by CLIP-seq) and reduces IRF1 protein expression post-transcriptionally, suppressing IRF1-dependent antiviral gene expression to enable viral replication. CLIP-seq (cross-linking immunoprecipitation + sequencing), loss-of-function screen, transcriptome profiling, Roquin knockdown/overexpression Proceedings of the National Academy of Sciences of the United States of America High 31451648
2016 DUSP1 overexpression elevates IRF1 mRNA and protein stability by suppressing MAPKs (which otherwise destabilize IRF1), thereby maintaining expression of IRF1-dependent genes including CXCL10; ChIP showed IRF1 recruitment to the CXCL10 promoter is essentially unaffected by dexamethasone despite DUSP1 induction. DUSP1 overexpression and siRNA silencing, MAPK inhibitors, mRNA stability assays, ChIP at CXCL10 and other IRF1-dependent promoters The Journal of biological chemistry Medium 27551049
2021 IRF1 governs differential ISG responses in human macrophages vs. monocytes: TLR4 signaling in macrophages uniquely engages IRF1, which facilitates chromatin opening at ISG loci for transcription; this lineage-specific chromatin remodeling function was not observed in monocytes. ATAC-seq (chromatin accessibility), RNA-seq, IRF1 KO in macrophages, TLR ligand stimulation panel, ChIP Cell reports High 33761354
2017 IRF1 and BATF serve as pioneering transcription factors during Tr1 cell differentiation: both are induced early by IL-27 and are required for chromatin accessibility and expression of Tr1 cell functional genes, as shown by epigenetic (ATAC-seq) and transcriptional analyses in IRF1- and BATF-deficient cells. ATAC-seq, RNA-seq, IRF1-deficient and BATF-deficient T cells, in vitro and in vivo Tr1 differentiation assays Nature immunology High 28166218
2023 IRF1-deficient mononuclear phagocytes fail to control mycobacteria and related intramacrophagic pathogens after IFN-γ stimulation; IFN-γ-dependent responses in IRF1-deficient leukocytes and fibroblasts are qualitatively and quantitatively much more impaired than IFN-α/β-dependent responses, demonstrating that IRF1 is essential for IFN-γ-dependent macrophagic immunity but largely redundant for IFN-α/β-dependent antiviral responses. IRF1-deficient patient cells (natural human genetic experiment), in vitro IFN-γ and IFN-α/β stimulation, mycobacterial killing assays, virus infection assays in fibroblasts Cell High 36736301
2023 IRF1 acts as an upstream transcriptional regulator of PANoptosome components: IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and PANoptosis (inflammatory cell death) in primary murine macrophages, but is dispensable for inflammasomes that form independently of the PANoptosome to drive pyroptosis alone. Live-cell imaging, Western blotting, ELISA, genetic IRF1 KO primary macrophages, multiple PANoptosome activation stimuli The Journal of biological chemistry Medium 37557956
2020 IRF1 transcriptionally suppresses PGC1α expression by binding to its promoter region (upregulated via H3K9 acetylation induced by high phosphate); restoration of PGC1α or genetic IRF1 knockdown attenuates high-phosphate-induced myocardial energy metabolism dysfunction. ChIP (IRF1 binding to PGC1α promoter), H3K9 acetylation analysis, IRF1 knockdown in vitro and KO mice in vivo, metabolic assays Nature communications High 32938919
2023 IRF1 binds to the promoter region of SLC7A11 (xCT) and suppresses its transcription, as confirmed by ChIP and luciferase reporter assays; loss of IRF1 increases SLC7A11, suppressing ferroptosis of hepatic stellate cells; this mechanism mediates GRh2-induced HSC ferroptosis and liver fibrosis attenuation. ChIP assay, luciferase reporter assay, IRF1 loss-of-function, SLC7A11 expression analysis, ferroptosis markers Phytomedicine Medium 37441987
2023 IRF1 directly binds the GBP5 promoter (confirmed by ChIP and dual luciferase assay) to enhance GBP5 expression; the IRF1/GBP5 axis promotes NLRP3 inflammasome-mediated chondrocyte pyroptosis and extracellular matrix degradation in osteoarthritis. Dual-luciferase reporter assay, ChIP, siRNA knockdown, adenoviral overexpression, NLRP3 inflammasome pathway readouts, DMM mouse model Journal of orthopaedic translation Medium 38229660
2024 Radiation-induced leakage of mitochondrial DNA (mtDNA) initiates nuclear translocation of IRF1; novel PTM sites in the IRF1 NLS were identified — mutation of an acetylation site and phosphorylation sites in the NLS blocked IRF1 transcriptional activation and reduced radiation-induced cell death. Reciprocal regulation between SSBP1 and IRF1 restrains STING/p300-mediated PTMs of IRF1. Site-directed mutagenesis of NLS PTM sites, mass spectrometry PTM identification, nuclear fractionation/translocation imaging, SSBP1-IRF1 co-IP, CRISPR KO, radiation and SARS-CoV-2 infection models Cellular & molecular immunology Medium 38849539
2015 IRF1 is required downstream of IRF8 for IL-1β expression in reactive microglia: peripheral nerve injury induces IRF1 gene expression in spinal microglia in an IRF8-dependent manner; IRF8 transduction in cultured microglia induces IRF1 de novo; and IRF1 knockdown in IRF8-transduced microglia prevents IL-1β upregulation. IRF8 viral transduction, IRF1 siRNA knockdown, in vivo spinal cord IRF1 expression analysis after nerve injury, qPCR/Western blot Journal of pharmacological sciences Medium 26318672
2016 IRF1 directly regulates IRG1 (immune-responsive gene 1/CAD) transcription: siRNA-mediated knockdown of IRF1 in macrophages significantly decreased IRG1/CAD gene and protein expression and correlated with reduced itaconic acid production. siRNA knockdown, RT-PCR, Western blot, itaconic acid measurement, gene regulatory network computational + experimental validation PloS one Medium 26872335
2012 IRF-1 transcriptionally regulates VCAM-1 expression in human aortic endothelial cells: overexpression of IRF-1 recapitulated proatherogenic upregulation of VCAM-1, while silencing of IRF-1 mimicked the antiatherogenic downregulation; IRF-1 and miR-126 were reciprocally modulated by postprandial triglyceride-rich lipoproteins. IRF-1 overexpression, siRNA silencing, miR-126 modulation, VCAM-1 expression assays in HAEC Circulation research Medium 22874466
2021 SARS-CoV-2 ORF6 protein suppresses IRF1 gene expression by blocking STAT1 signaling (type II interferon-mediated), which prevents IRF1 upregulation of NLRC5 and MHC class I pathway genes; ORF6 also blocks karyopherin complex-dependent nuclear import of NLRC5. SARS-CoV-2-infected epithelial cell lines, COVID-19 patient gene expression, ORF6 overexpression, JAK-STAT reporter assays, nuclear import assays Nature communications Medium 34782627
2023 PARP7 is a nuclear, cysteine-specific mono-ADP-ribosyltransferase that modifies FRA1 (AP-1 transcription factor) at C97; loss of FRA1 ADP-ribosylation promotes FRA1 degradation via PSMC3, which de-represses IRF1- and IRF3-dependent proapoptotic and cytokine gene expression, culminating in CASP8-mediated apoptosis. PARP7 inhibition (RBN-2397), C97 mutation of FRA1, proteasome inhibition, IRF1/IRF3-dependent reporter assays, mass spectrometry for ADP-ribosylation sites Proceedings of the National Academy of Sciences of the United States of America Medium 38011562
2023 IRF1 regulates ZBP1 transcription in an IRF1-dependent manner downstream of TNF-α; IRF1-driven ZBP1 overexpression is activated by mitochondrial DNA binding to ZBP1; activated ZBP1 interacts with RIPK1 and activates TAK1-NF-κB signaling, leading to chondrocyte inflammation and matrix degradation in osteoarthritis. IRF1 KD in chondrocytes, ZBP1 KD, DMM mouse model, co-immunoprecipitation (ZBP1-RIPK1), Cyclosporine A (mtDNA release blocker), Western blot Cell communication and signaling Medium 39026271
2023 IRF1 loss in mouse HSCs significantly impairs self-renewal, increases stress-induced proliferation, and confers resistance to apoptosis, establishing IRF1 as a pivotal regulator of HSC homeostasis. Conditional IRF1 KO in mouse HSCs, transplantation assays, stress-induced proliferation assays, apoptosis measurement Science advances Medium 37889967
2024 IRF1 binds to the promoter of GPX4 indirectly by interacting with SPI1 (PU.1) and suppressing SPI1's transcriptional activating effect on GPX4 expression, thereby reducing GPX4 levels, increasing lipid ROS accumulation, and enhancing ferroptosis in colon cancer cells. Co-immunoprecipitation (IRF1-SPI1 interaction), ChIP (SPI1 binding to GPX4 promoter), luciferase reporter assay, IRF1/SPI1 overexpression and knockdown, ferroptosis markers Experimental cell research Medium 37517591
2022 IFIH1 promotes IRF1 translocation into the nucleus in macrophages during infection; nuclear IRF1 then binds to the STAT1 promoter (confirmed by ChIP-seq) and activates STAT1 transcription, contributing to macrophage M1 polarization and septic lung injury. ChIP-seq (IRF1 binding to STAT1 promoter), IRF1 KO mice (CLP model), shRNA knockdown, nuclear fractionation, immunohistochemistry International immunopharmacology Medium 36462334
2020 iNOS/NO promotes IRF1 nuclear translocation and transcriptional activity through HDAC2-mediated histone H3 deacetylation (H3K9 hypoacetylation) at IRF1 target gene promoters; iNOS KO mice show impaired IRF1 nuclear translocation and reduced PUMA expression after hepatic I/R injury. iNOS KO mice (I/R model), iNOS overexpression, NO donors, HDAC inhibitor (romidepsin), nuclear fractionation for IRF1, H3AcK9 Western blot, IRF1 reporter assay Molecular medicine Medium 32517688

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Activities of IRF-1. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 232 11846971
1995 Chromatin domains and prediction of MAR sequences. International review of cytology 197 8575883
1998 SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. Nucleic acids research 155 9671816
2002 IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Immunity 140 12479817
2002 Regulation of PKR and IRF-1 during hepatitis C virus RNA replication. Proceedings of the National Academy of Sciences of the United States of America 139 11904369
2021 SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis. Nature communications 135 34782627
2002 The multiple antibiotic resistance (mar) locus and its significance. Research in veterinary science 115 12027588
2002 IRF-1 as a negative regulator of cell proliferation. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 110 11846974
2023 Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity. Nature cancer 108 36894639
2020 Indoxyl sulfate induces intestinal barrier injury through IRF1-DRP1 axis-mediated mitophagy impairment. Theranostics 106 32641998
2021 NF-κB-dependent IRF1 activation programs cDC1 dendritic cells to drive antitumor immunity. Science immunology 101 34244313
2014 DTX3L and ARTD9 inhibit IRF1 expression and mediate in cooperation with ARTD8 survival and proliferation of metastatic prostate cancer cells. Molecular cancer 97 24886089
2017 Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation. Nature immunology 96 28166218
2023 Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria. Cell 93 36736301
2023 Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis). The Journal of biological chemistry 91 37557956
2015 Batf2/Irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection. Journal of immunology (Baltimore, Md. : 1950) 89 25957166
2012 IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal. Circulation research 88 22874466
2020 Verteporfin Inhibits PD-L1 through Autophagy and the STAT1-IRF1-TRIM28 Signaling Axis, Exerting Antitumor Efficacy. Cancer immunology research 87 32265228
2018 The MAR databases: development and implementation of databases specific for marine metagenomics. Nucleic acids research 85 29106641
2004 Identification of a novel plant MAR DNA binding protein localized on chromosomal surfaces. Plant molecular biology 85 15604740
2019 IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response. Frontiers in immunology 82 31156620
2016 Effects of IRF1 and IFN-β interaction on the M1 polarization of macrophages and its antitumor function. International journal of molecular medicine 79 27176664
1998 Functional domains of interferon regulatory factor I (IRF-1). The Biochemical journal 79 9742224
2016 Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages. PloS one 76 26872335
2019 IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell. Cancer immunology research 71 31239318
2023 Ferroptosis triggered by STAT1- IRF1-ACSL4 pathway was involved in radiation-induced intestinal injury. Redox biology 68 37611494
2021 IRF1 governs the differential interferon-stimulated gene responses in human monocytes and macrophages by regulating chromatin accessibility. Cell reports 66 33761354
2022 IFIH1/IRF1/STAT1 promotes sepsis associated inflammatory lung injury via activating macrophage M1 polarization. International immunopharmacology 61 36462334
1996 Expression of the protein kinase PKR in modulated by IRF-1 and is reduced in 5q- associated leukemias. Oncogene 61 8622878
2020 IRF1-mediated downregulation of PGC1α contributes to cardiorenal syndrome type 4. Nature communications 59 32938919
1999 Activation and repression of the 2-5A synthetase and p21 gene promoters by IRF-1 and IRF-2. Oncogene 59 10321737
2022 SPOP mutations promote tumor immune escape in endometrial cancer via the IRF1-PD-L1 axis. Cell death and differentiation 51 36481790
2020 IRF1 Promotes the Innate Immune Response to Viral Infection by Enhancing the Activation of IRF3. Journal of virology 51 32878885
2019 Transcriptional regulation of homeostatic and disease-associated-microglial genes by IRF1, LXRβ, and CEBPα. Glia 51 31301160
2021 SOX10 Regulates Melanoma Immunogenicity through an IRF4-IRF1 Axis. Cancer research 49 34728538
2020 miR-130b-3p regulates M1 macrophage polarization via targeting IRF1. Journal of cellular physiology 47 32853398
2023 Ginsenoside Rh2 promotes hepatic stellate cell ferroptosis and inactivation via regulation of IRF1-inhibited SLC7A11. Phytomedicine : international journal of phytotherapy and phytopharmacology 46 37441987
2018 IRF1 supports DNA binding of STAT1 by promoting its phosphorylation. Immunology and cell biology 45 29893425
2014 Osteopontin enhances the expression of HOTAIR in cancer cells via IRF1. Biochimica et biophysica acta 45 24999034
2019 Interferon-inducible lncRNA IRF1-AS represses esophageal squamous cell carcinoma by promoting interferon response. Cancer letters 43 31173852
2016 STAT3/IRF1 Pathway Activation Sensitizes Cervical Cancer Cells to Chemotherapeutic Drugs. Cancer research 42 27216197
2015 Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia. Journal of pharmacological sciences 41 26318672
2022 Non-canonical NF-κB contributes to endothelial pyroptosis and atherogenesis dependent on IRF-1. Translational research : the journal of laboratory and clinical medicine 38 36384204
2017 Properties of STAT1 and IRF1 enhancers and the influence of SNPs. BMC molecular biology 38 28274199
2000 Interferons and IRF-1 induce expression of the survival motor neuron (SMN) genes. Molecular medicine (Cambridge, Mass.) 38 11147573
2023 PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis. Proceedings of the National Academy of Sciences of the United States of America 37 38011562
2018 miR-383 promotes cholangiocarcinoma cell proliferation, migration, and invasion through targeting IRF1. Journal of cellular biochemistry 37 30145803
1996 Binding of MAR-DNA elements by mutant p53: possible implications for its oncogenic functions. Journal of cellular biochemistry 36 8844397
2007 IRF-1 gene variations influence IgE regulation and atopy. American journal of respiratory and critical care medicine 35 18079498
2022 An IRF1-dependent Pathway of TNFα-induced Shedding in Intestinal Epithelial Cells. Journal of Crohn's & colitis 34 34309645
2018 IRF1 inhibits the proliferation and metastasis of colorectal cancer by suppressing the RAS-RAC1 pathway. Cancer management and research 33 30643462
2010 A mini review of MAR-binding proteins. Molecular biology reports 33 20174991
2009 Minicircle performance depending on S/MAR-nuclear matrix interactions. Journal of molecular biology 33 20004666
2014 Oncogenic Ras inhibits IRF1 to promote viral oncolysis. Oncogene 32 25347735
2023 The IRF1/GBP5 axis promotes osteoarthritis progression by activating chondrocyte pyroptosis. Journal of orthopaedic translation 30 38229660
2015 Interferon-regulatory factor-1 (IRF1) regulates bevacizumab induced autophagy. Oncotarget 29 26362401
2013 MAR elements and transposons for improved transgene integration and expression. PloS one 29 23646143
2023 IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance. Science advances 28 37889967
2019 Multiple Antibiotic Resistance (MAR), Plasmid Profiles, and DNA Polymorphisms among Vibrio vulnificus Isolates. Antibiotics (Basel, Switzerland) 28 31141983
2024 Chaperone- and PTM-mediated activation of IRF1 tames radiation-induced cell death and the inflammatory response. Cellular & molecular immunology 27 38849539
2021 CITED2 inhibits STAT1-IRF1 signaling and atherogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 34365659
2022 Effective gene therapy of Stargardt disease with PEG-ECO/pGRK1-ABCA4-S/MAR nanoparticles. Molecular therapy. Nucleic acids 25 36159595
2019 GSK3β-SCFFBXW7α mediated phosphorylation and ubiquitination of IRF1 are required for its transcription-dependent turnover. Nucleic acids research 25 30854564
2013 DNA-binding regulates site-specific ubiquitination of IRF-1. The Biochemical journal 25 23134341
2008 Regulation of STAT pathways and IRF1 during human dendritic cell maturation by TNF-alpha and PGE2. Journal of leukocyte biology 25 18678606
2020 In Primitive Zebrafish, MHC Class II Expression Is Regulated by IFN-γ, IRF1, and Two Forms of CIITA. Journal of immunology (Baltimore, Md. : 1950) 24 32188757
2015 Inhibition of SGK1 enhances mAR-induced apoptosis in MCF-7 breast cancer cells. Cancer biology & therapy 23 25427201
2012 SIRT1 deacetylates SATB1 to facilitate MAR HS2-MAR ε interaction and promote ε-globin expression. Nucleic acids research 23 22328728
2015 MAR characteristic motifs mediate episomal vector in CHO cells. Gene 22 25598284
2011 Non-viral episomal modification of cells using S/MAR elements. Expert opinion on biological therapy 22 21548848
2006 The role of IRF1 and IRF2 transcription factors in leukaemogenesis. Current gene therapy 22 17073600
2023 IRF1 suppresses colon cancer proliferation by reducing SPI1-mediated transcriptional activation of GPX4 and promoting ferroptosis. Experimental cell research 21 37517591
2021 IRF1 regulates the progression of colorectal cancer via interferon‑induced proteins. International journal of molecular medicine 21 33907823
2020 IRF-1 Inhibits Angiogenic Activity of HPV16 E6 Oncoprotein in Cervical Cancer. International journal of molecular sciences 21 33076322
2020 IFI44L expression is regulated by IRF-1 and HIV-1. FEBS open bio 21 33159419
2016 DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes: A MECHANISM PROMOTING GLUCOCORTICOID INSENSITIVITY. The Journal of biological chemistry 21 27551049
2014 Restoration of IRF1-dependent anticancer effects by MEK inhibition in human cancer cells. Cancer letters 21 25497010
2024 Opposing tumor-cell-intrinsic and -extrinsic roles of the IRF1 transcription factor in antitumor immunity. Cell reports 20 38833371
2024 IRF1 regulation of ZBP1 links mitochondrial DNA and chondrocyte damage in osteoarthritis. Cell communication and signaling : CCS 20 39026271
2017 HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections. The Journal of experimental medicine 20 28970238
2016 MAR-Mediated transgene integration into permissive chromatin and increased expression by recombination pathway engineering. Biotechnology and bioengineering 20 27575535
2001 Alterations in IRF1/IRF2 expression in acute myelogenous leukemia. American journal of hematology 20 11559933
2022 XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity. Journal of virology 19 35972291
2022 HDAC8 Promotes Liver Metastasis of Colorectal Cancer via Inhibition of IRF1 and Upregulation of SUCNR1. Oxidative medicine and cellular longevity 19 36035205
2024 TNF and IFNγ-induced cell death requires IRF1 and ELAVL1 to promote CASP8 expression. The Journal of cell biology 18 38319288
2023 Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways. International immunopharmacology 18 36931170
2021 IFN-γ Induces IL-15 Trans-Presentation by Epithelial Cells via IRF1. Journal of immunology (Baltimore, Md. : 1950) 18 34893528
2003 IL12B and IRF1 gene polymorphisms and susceptibility to celiac disease. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 18 14675396
2024 Sulforaphane improves post-resuscitation myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the Nrf2/IRF1/GPX4 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 39244999
2021 TNF-Mediated Inhibition of Classical Swine Fever Virus Replication Is IRF1-, NF-κB- and JAK/STAT Signaling-Dependent. Viruses 17 34696447
2019 IRF1 and IRF2 regulate the non-canonical inflammasome. EMBO reports 17 31379068
2014 Episomal maintenance of S/MAR-containing non-viral vectors for RPE-based diseases. Advances in experimental medicine and biology 17 24664761
2020 iNOS/NO is required for IRF1 activation in response to liver ischemia-reperfusion in mice. Molecular medicine (Cambridge, Mass.) 16 32517688
2019 Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state. Proceedings of the National Academy of Sciences of the United States of America 16 31451648
2019 IRF1 Negatively Regulates Oncogenic KPNA2 Expression Under Growth Stimulation and Hypoxia in Lung Cancer Cells. OncoTargets and therapy 16 31920336
2018 FOXM1c promotes oesophageal cancer metastasis by transcriptionally regulating IRF1 expression. Cell proliferation 16 30485581
2023 ABCA1 deficiency contributes to podocyte pyroptosis priming via the APE1/IRF1 axis in diabetic kidney disease. Scientific reports 15 37316538
2020 IRF-1 mediates the suppressive effects of mTOR inhibition on arterial endothelium. Journal of molecular and cellular cardiology 15 32087218
2022 Interferon regulatory factor 1 (IRF1) controls the metabolic programmes of low-grade pancreatic cancer cells. Gut 14 35568393
2020 Maternal-Autoantibody-Related (MAR) Autism: Identifying Neuronal Antigens and Approaching Prospects for Intervention. Journal of clinical medicine 14 32784803

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