Affinage

IFIT3

Interferon-induced protein with tetratricopeptide repeats 3 · UniProt O14879

Length
490 aa
Mass
56.0 kDa
Annotated
2026-06-10
81 papers in source corpus 31 papers cited in narrative 31 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

IFIT3 is an interferon-induced TPR-domain protein that functions as a multivalent scaffold coordinating innate immune signaling and direct antiviral effector activity (PMID:21813773, PMID:29554348). In RNA-sensing signaling it bridges MAVS and TBK1, with its TPR motif (E164/E165) contacting the TBK1 N-terminus (K38) to promote TBK1 activation and IRF3 phosphorylation (PMID:21813773); downstream of cGAS, it binds STING and TBK1 to drive IFNβ expression (PMID:29806091) and acts as a bridge between STING and the deubiquitinase USP18 to block STING degradation and amplify inflammatory signaling (PMID:41686220). IFIT3 also potentiates the IFN-α effector arm by binding STAT1 and STAT2 to enhance STAT1–STAT2 heterodimerization and nuclear translocation and ISG induction (PMID:28295457, PMID:36314949). As a direct effector, IFIT3 partners with the other IFITs: it heterodimerizes with IFIT1 through a C-terminal YxxxL motif, stabilizing IFIT1 against proteasomal degradation and allosterically reshaping the IFIT1 RNA-binding channel to sharpen specificity for cap-0 (2'-O-unmethylated) viral RNA [PMID:29525521, PMID:29554348, PMID:bio_10.1101_2025.11.17.688928], a sensing function confirmed against 2'-O-methyltransferase-deficient SARS-CoV-2 (PMID:36722972); in a domain-swapped heterodimer with IFIT2 it recognizes viral mRNAs bearing short (<50 nt) 5' UTRs and inhibits their translation (PMID:41093992). IFIT3 binds RNA directly through a conserved surface and TPR-resident elements, a property separable from dimerization and required for its RNA-dependent activities (PMID:40497724, PMID:41929069). The protein is itself a regulatory target: it is ubiquitinated by UBE2O at K236 for proteasomal turnover (PMID:38129382) and is cleaved by coronaviral nsp5 main proteases at a defined site to antagonize type I IFN signaling (PMID:38289117). Beyond antiviral defense, IFIT3 sequesters JAB1/CSN5 to perturb the COP9 signalosome and cullin-RING ligase activity, stabilizing p27 and driving G1/S arrest (PMID:17050680, PMID:23415865), and in cancer contexts engages partners including VDAC2, ANXA2, LASP1, and DVL2 to modulate apoptosis, EGFR recycling, FAK-ERK, and canonical WNT signaling (PMID:32641986, PMID:30626937, PMID:41850400, PMID:41413015).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2006 High

    Established the first mechanistic role for IFIT3 outside antiviral defense, showing it controls cell cycle progression by acting on the ubiquitin/proteasome machinery.

    Evidence Co-IP, ectopic expression and proteasome inhibition in U937 cells linking IFIT3/JAB1 binding to p27 stabilization

    PMID:17050680

    Open questions at the time
    • Did not define the IFIT3 residues mediating JAB1 binding
    • Relationship between this growth-arrest role and antiviral signaling unresolved
  2. 2010 Medium

    Defined how IFIT3 transcription is induced, showing it is an ISRE-driven gene amplified by but not strictly dependent on the classical JAK-STAT pathway, and confirmed its contribution to IFN-α antiviral protection.

    Evidence STAT1-deficient cell reconstitution with IRF-1/IRF-9/STAT2 perturbation and luciferase reporters; siRNA/overexpression antiviral titer assays

    PMID:20686046 PMID:21056555

    Open questions at the time
    • The 2010 antiviral study identified no molecular mechanism for restriction
    • Did not distinguish IFIT3 effector versus signaling contributions
  3. 2011 High

    Answered how IFIT3 links upstream sensing to kinase activation, identifying it as a scaffold that physically bridges MAVS and TBK1 to promote IRF3 phosphorylation.

    Evidence Reciprocal Co-IP with E164/E165 and TBK1 K38 mutagenesis, siRNA knockdown, and IRF3 phosphorylation/antiviral assays

    PMID:21813773

    Open questions at the time
    • Did not address whether the same TPR surface engages STING-pathway components
    • Stoichiometry within the MAVS complex not defined
  4. 2013 Medium

    Extended IFIT3's effect on the ubiquitin system, showing it disrupts COP9 signalosome integrity and thereby deregulates cullin-RING ligase activity and IκBα turnover.

    Evidence Co-IP, deneddylation/ubiquitination assays and Western blot of CSN subunits/Cul1/βTrCP after ectopic IFIT3 expression

    PMID:23415865

    Open questions at the time
    • No mutagenesis to define the IFIT3 surface disrupting CSN
    • Reliance on overexpression leaves physiological relevance open
  5. 2017 Medium

    Showed IFIT3 acts on the IFN effector limb, binding STAT1 and STAT2 to enhance their heterodimerization and nuclear translocation.

    Evidence Reciprocal Co-IP, nuclear fractionation, and KD/OE with antitumor assays in HCC cells

    PMID:28295457

    Open questions at the time
    • Did not map the STAT-binding region of IFIT3
    • Direct versus indirect nature of the STAT interaction not resolved
  6. 2018 High

    Resolved the structural and regulatory basis of IFIT1–IFIT3 partnership, showing IFIT3's C-terminal domain stabilizes IFIT1 and allosterically reshapes its channel to enforce cap-0 RNA specificity.

    Evidence X-ray crystallography of cap-0 RNA–IFIT1–IFIT3 CTD with binding, half-life and viral restriction assays; in vitro IFIT complex reconstitution with YxxxL mutagenesis and EMSA

    PMID:29525521 PMID:29554348

    Open questions at the time
    • Mouse Ifit3 lacks the relevant CTD, complicating model-organism extrapolation
    • How IFIT2/IFIT3 versus IFIT1/IFIT3 complex choice is governed not defined here
  7. 2018 Medium

    Placed IFIT3 within the cytosolic DNA-sensing pathway, showing it interacts with STING and TBK1 to drive IFNβ downstream of cGAS/STING.

    Evidence Co-IP of IFIT3 with STING and TBK1 and gain/loss-of-function IFNβ assays in human monocytes

    PMID:29806091

    Open questions at the time
    • Interaction interfaces with STING/TBK1 not mapped
    • Whether STING and MAVS scaffolding use the same IFIT3 surface unknown
  8. 2023 Medium

    Identified the degradation control of IFIT3 itself, defining UBE2O-mediated ubiquitination at K236 as a checkpoint limiting IFN-α efficacy.

    Evidence MS, Co-IP, K236A mutagenesis rescue and KD/OE functional assays in hepatocellular carcinoma

    PMID:38129382

    Open questions at the time
    • E3 ligase cooperating with UBE2O not identified
    • Signals triggering IFIT3 degradation undefined
  9. 2024 High

    Revealed a viral evasion strategy targeting IFIT3, showing coronaviral nsp5 proteases cleave it at a defined residue to disable type I IFN signaling.

    Evidence In vitro cleavage assays with Q406A mutagenesis across multiple coronavirus nsp5 proteins and viral replication assays

    PMID:38289117

    Open questions at the time
    • Functional consequence of cleavage fragments not characterized
    • Whether cleavage abolishes scaffolding or effector functions selectively unresolved
  10. 2025 High

    Defined IFIT3's intrinsic RNA-binding activity and its targets, showing direct RNA binding through a conserved surface and TPR elements, separable from dimerization and including preferential m6A-modified RNA recognition.

    Evidence Cryo-EM of the domain-swapped IFIT2-IFIT3 heterodimer with translation assays; EMSA/RBS-ID mutagenesis for IAV; HyperTRIBE-seq and TPR/hairpin mutagenesis for m6A/HCV RNA (preprint)

    PMID:40497724 PMID:41093992 PMID:41929069

    Open questions at the time
    • Pro-viral versus antiviral outcomes of IFIT3 RNA binding context-dependent and not unified
    • m6A-dependence characterized only in preprint form
  11. 2025 Medium

    Showed why IFIT1 accumulation is coupled to IFIT3, demonstrating that IFIT3 protects IFIT1 from degradation and rescues self ISG mRNAs from IFIT1-mediated translation inhibition, preventing self-targeting.

    Evidence Ectopic IFIT1±IFIT3 expression, proteasome inhibition, translation and viral replication assays (preprint)

    PMID:bio_10.1101_2025.11.17.688928

    Open questions at the time
    • Not yet peer-reviewed
    • Quantitative thresholds distinguishing self versus viral RNA discrimination undefined
  12. 2026 Medium

    Refined IFIT3's role in STING signaling, showing it bridges STING and USP18 to block STING ubiquitination and amplify inflammatory output.

    Evidence Co-IP of the IFIT3/STING/USP18 complex, ubiquitination assays and AAV-mediated in vivo knockdown affecting lung injury and M1 polarization

    PMID:41686220

    Open questions at the time
    • Direct versus bridged contacts within the ternary complex partially inferred
    • Whether USP18 acts catalytically or stoichiometrically on STING not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IFIT3 partitions between its many roles — antiviral effector, signaling scaffold, and pro-tumorigenic partner — and what determines which complexes (IFIT1, IFIT2, STING/TBK1, STAT, VDAC2, ANXA2, LASP1, DVL2) it forms in a given cell remains unresolved.
  • No unified model reconciling antiviral and pro-viral/pro-tumor activities
  • Determinants of complex selection in vivo unknown
  • Most cancer-context partners rest on single-lab Co-IP without structural validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0045182 translation regulator activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 1
Partners
IFIT1IFIT2JAB1STAT1STAT2STINGTBK1USP18
Complex memberships
COP9 signalosome (disrupts)IFIT1-IFIT3 heterodimerIFIT2-IFIT3 heterodimer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 IFIT3 bridges MAVS and TBK1 on mitochondria to potentiate antiviral signaling: the TPR motif (E164/E165) of IFIT3 interacts with the N-terminus (K38) of TBK1, physically linking TBK1 to the MAVS complex and promoting TBK1 activation and IRF3 phosphorylation. Disruption of this interaction attenuates TBK1 and IRF3 activation. Co-immunoprecipitation, ectopic expression, siRNA knockdown, mutagenesis (E164/E165 and K38), IRF3 phosphorylation assays, antiviral replication assays Journal of immunology High 21813773
2018 Crystal structure of cap 0 RNA bound to human IFIT1 in complex with the C-terminal domain of human IFIT3 reveals that IFIT3 binding to IFIT1 has dual regulatory functions: (1) extending IFIT1 half-life (increasing steady-state protein levels) and (2) allosterically reshaping the IFIT1 RNA-binding channel to enhance specificity for cap 0 but not cap 1 or 5'-ppp RNA. Mouse Ifit3 lacks this C-terminal domain and does not bind mouse Ifit1. X-ray crystallography, biochemical binding assays, mutagenesis, cell-based half-life/stability assays, viral restriction assays with 2'-O methylation-deficient viruses Immunity High 29525521
2018 IFIT1 and IFIT3 interact via a conserved YxxxL motif in the C-terminus of each protein. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that also associates with IFIT1. IFIT3 stabilizes IFIT1 protein expression, promotes IFIT1 binding to cap0 Zika virus reporter mRNA, and enhances IFIT1-mediated translation inhibition. In vitro reconstitution of IFIT complexes, electrophoretic mobility shift assays (EMSA), mutagenesis (YxxxL motif), translation inhibition assays, protein stability assays Nucleic acids research High 29554348
2006 RIG-G (IFIT3) induces G1/S cell cycle arrest by interacting with JAB1 (CSN5), sequestering it and preventing JAB1-dependent, ubiquitin/proteasome-mediated degradation of p27, thereby elevating p27 levels. Additionally, RIG-G causes c-Myc downregulation, leading to p21 upregulation, contributing to growth arrest. Ectopic expression in U937 cells, Co-immunoprecipitation (RIG-G/JAB1 interaction), cell cycle analysis (flow cytometry), Western blot for p21/p27/c-Myc, ubiquitin/proteasome inhibition experiments Proceedings of the National Academy of Sciences of the United States of America High 17050680
2013 RIG-G (IFIT3) disrupts the integrity and stability of the COP9 signalosome (CSN) complex, dramatically reducing cellular CSN content and inhibiting its regulatory roles in assembly and activation of cullin-RING ubiquitin E3 ligases (CRL). This causes excessive CRL activation (via CSN-mediated deneddylation inhibition), decreasing Cul1 and βTrCP levels, and impairing CSN-associated deubiquitination (USP15 recruitment), resulting in accumulation of IκBα. Co-immunoprecipitation, Western blot for CSN subunits/Cul1/βTrCP/IκBα, deneddylation assays, ubiquitination assays, ectopic expression of RIG-G Biochemical and biophysical research communications Medium 23415865
2017 IFIT3 binds STAT1 and STAT2 to enhance STAT1-STAT2 heterodimerization and nuclear translocation upon IFN-α treatment, thereby promoting IFN-α effector signaling. This was demonstrated by co-immunoprecipitation in HCC cells and confirmed functionally in vitro and in vivo. Co-immunoprecipitation (IFIT3/STAT1 and IFIT3/STAT2), nuclear fractionation, ectopic expression and knockdown, in vitro and in vivo antitumor assays Hepatology Medium 28295457
2018 IFIT3 interacts with both STING and TBK1, and promotes IFNβ expression downstream of the cGAS/STING pathway. Knockdown of IFIT3 reduced VACV70-induced IFNβ expression, while overexpression produced an opposite effect. Co-immunoprecipitation (IFIT3/STING and IFIT3/TBK1), gain- and loss-of-function experiments, IFNβ expression assays in human monocytes Arthritis & rheumatology Medium 29806091
2020 IFIT3 directly interacts with the mitochondrial channel protein VDAC2, and stabilizes the interaction of VDAC2 with O-GlcNAc transferase (OGT), promoting O-GlcNAcylation of VDAC2. This increased VDAC2 O-GlcNAcylation protects PDAC cells from chemotherapy-induced apoptosis, conferring drug resistance. Co-immunoprecipitation, mass spectrometry, subcellular fractionation, confocal immunofluorescence, knockdown/overexpression, apoptosis assays, chromatin-immunoprecipitation Theranostics Medium 32641986
2019 IFIT1 and IFIT3 interact with ANXA2 (Annexin A2) by co-immunoprecipitation and LC-MS/MS, and this interaction enhances endosomal recycling of phosphorylated EGFR (p-EGFRY1068). Depletion of ANXA2 abolished p-EGFR and p-AKT expression in IFIT1- or IFIT3-overexpressing OSCC cells. Co-immunoprecipitation, LC-MS/MS, siRNA knockdown of ANXA2, Western blot for p-EGFR/p-AKT, xenograft and orthotopic mouse models Oncogene Medium 30626937
2023 UBE2O ubiquitinates IFIT3 at lysine 236 (K236), targeting it for proteasomal degradation and reducing IFN-α signaling efficacy in hepatocellular carcinoma. Knockdown of UBE2O increased IFIT3 expression and enhanced IFN-α antitumor effects; rescue experiments with K236 mutant IFIT3 confirmed dependence on this ubiquitination site. Proteomic analysis, mass spectrometry, co-immunoprecipitation, mutagenesis (K236A), knockdown/overexpression, in vitro and in vivo functional assays Cell death & disease Medium 38129382
2024 PDCoV nsp5 (main protease) cleaves porcine IFIT3 at Gln-406, antagonizing type I interferon signaling. A pIFIT3-Q406A mutant was resistant to nsp5-mediated cleavage and exhibited greater ability to inhibit PDCoV infection than wild-type IFIT3. Similar cleavage of endogenous IFIT3 by nsp5 proteins of multiple human coronaviruses (but not alphacoronaviruses) was observed. Transcriptomic analysis, site-directed mutagenesis (Q406A), in vitro cleavage assays, ectopic expression, viral replication assays, Western blot Journal of virology High 38289117
2025 The IFIT2-IFIT3 heterodimer, formed through a domain-swapped structure resolved by cryo-EM at 3.2 Å, recognizes viral mRNA 5' ends with short untranslated regions (<50 nucleotides) as a molecular pattern, inhibiting their translation. This complex mediates antiviral activity against viruses with short 5' UTRs (e.g., VSV, parainfluenza virus 3). Cryo-EM structure determination (3.2 Å), in vitro translation inhibition assays, mutagenesis, viral replication assays Nature microbiology High 41093992
2025 IFIT3 directly binds RNA via a conserved surface composed of residues shared with IFIT2 paralogs, located near the dimerization interface. Mutation of this RNA-binding surface reduced IFIT3's ability to promote IAV gene expression and translation efficiency without affecting IFIT2/IFIT3 dimerization, establishing that RNA binding is functionally separable from dimerization and required for pro-viral activity during IAV infection. Electrophoretic mobility shift assay (EMSA), RNA-binding site identification (RBS-ID), mutagenesis, co-immunoprecipitation, IAV replication/translation assays Journal of virology High 40497724
2023 IFIT3 mediates TBK1 phosphorylation as an upstream regulatory factor, activating plasmacytoid dendritic cells (pDCs) and contributing to SSc pathogenesis. IFIT3-knockout mice showed reduced skin and lung fibrosis in the SSc model. Single-cell RNA sequencing, in vitro cell experiments, CRISPR/Cas9 IFIT3-knockout mouse model, TBK1 phosphorylation assays, cytokine measurements Clinical and translational medicine Medium 39305055
2022 IFIT3 promotes the anti-HBV effect of IFN-α in a STAT2-dependent manner: knockdown of IFIT3 inhibited STAT2 phosphorylation while overexpression promoted it, and IFIT3 overexpression enhanced IFN-α-triggered ISG expression (MxA, OAS1, PKR). This effect was abrogated by JAK inhibitor ruxolitinib. shRNA knockdown, overexpression, Western blot for pSTAT2, qRT-PCR for ISGs, HBV antigen/DNA quantification, ruxolitinib epistasis experiment Microbiology spectrum Medium 36314949
2016 HSV-1 tegument protein UL41, a viral endoribonuclease, counteracts IFIT3 antiviral activity by degrading IFIT3 mRNA, reducing its accumulation. UL41-null mutant HSV-1 replication was restricted by ectopic IFIT3, and stable IFIT3 knockdown facilitated UL41-null virus replication. Ectopic expression of UL41, UL41-null mutant virus (R2621), stable IFIT3 knockdown, mRNA quantification, viral replication assays Journal of virology Medium 27681138
2023 IFIT1 and IFIT3 form a complex with BAX and N-GSDME, directing N-GSDME translocation to mitochondria and increasing mitochondrial membrane permeabilization, thereby triggering pyroptosis in myeloma and leukemia cells. Co-immunoprecipitation, RNA sequencing, siRNA knockdown, caspase/GSDME activation assays, mitochondrial fractionation, venetoclax combination experiments Cancer letters Medium 38462032
2019 HBV regulatory protein HBx activates NF-κB, which in turn directly drives IFIT3 transcription, and overexpressed IFIT3 paradoxically enhances HBV replication in HepG2 cells. Transfection with pHBV1.3 plasmid, NF-κB activation assays, IFIT3 overexpression, HBV replication assays Frontiers in microbiology Low 31681236
2018 IFIT3 (ISG60) constitutes a negative feedback loop downstream of TLR3/IFN-β signaling in brain capillary endothelial cells: knockdown of IFIT3 increased poly IC-induced IFN-β and CXCL10 expression, demonstrating that IFIT3 limits these responses. siRNA knockdown of ISG60, poly IC treatment, ELISA/qRT-PCR for IFN-β and CXCL10 Journal of neuroimmunology Low 30195920
2015 IFIT3 shows binding to JNK and STAT1 in pancreatic cancer cells (COLO357FG), and STAT1 is an important inducer of IFIT3 expression. Transgenic IFIT3 expression increased VEGF and IL-6 secretion, chemoresistance, and decreased starvation-induced apoptosis. Co-immunoprecipitation (IFIT3/JNK and IFIT3/STAT1), ectopic expression, in vitro/in vivo tumor assays, cytokine quantification Oncotarget Low 25650658
2010 STAT1 significantly enhances the IRF-9/STAT2 complex or IRF-1 on RIG-G (IFIT3) induction through the activated JAK-STAT pathway; however, STAT1 is not essential for RIG-G expression. In STAT1-deficient cells, IRF-1 can induce RIG-G expression via ISREs, but cannot upregulate IRF-9 and STAT2 unless STAT1 is reconstituted. RIG-G expression is independent of the classical JAK-STAT pathway but greatly amplified by it. STAT1-deficient U3A cell reconstitution, luciferase reporter assays, Western blot, IRF-1/IRF-9/STAT2 overexpression Experimental cell research Medium 21056555
2025 IFIT3 preferentially associates with N6-methyladenosine (m6A)-modified HCV genomic RNA and host transcripts to restrict HCV infection. Two structural regions are required for RNA binding: TPR1-2 (required for IFIT2 interaction but dispensable for HCV RNA binding) and a predicted helical hairpin between TPR6 and TPR7 (required for HCV RNA binding but dispensable for IFIT2 interaction). Loss of either region diminished antiviral activity. HyperTRIBE-seq (transcriptome-wide RNA-binding site mapping), co-purification with m6A-modified RNA probes, m6A inhibition experiments, mutagenesis of TPR domains and helical hairpin, HCV replication assays bioRxiv (preprint)preprint Medium 41929069
2025 When IFIT1 is expressed at high levels without IFIT3, it can inhibit translation of certain self ISG mRNAs (including ISG15 and IFITM1). IFIT1:IFIT3 complex formation rescues these self-ISGs from IFIT1-mediated translation inhibition. IFIT3 directly binds IFIT1 and protects it from proteasomal degradation, ensuring IFIT1 accumulation only occurs alongside IFIT3—a mechanism to prevent self-targeting while enabling antiviral activity. Ectopic expression of IFIT1 with/without IFIT3, siRNA knockdown, proteasome inhibitor experiments, translation assays, viral replication assays (Semliki Forest virus) bioRxiv (preprint)preprint Medium bio_10.1101_2025.11.17.688928
2026 IFIT3 acts as a molecular bridge between STING and the deubiquitinase USP18, inhibiting ubiquitination-mediated degradation of STING and amplifying downstream cGAS-STING inflammatory signaling. IFIT3 promoted M1 macrophage polarization and early lung injury; IFIT3 knockdown ameliorated early lung injury in vivo. Co-immunoprecipitation (IFIT3/STING/USP18), ubiquitination assays, IFIT3 knockdown in vivo (AAV-mediated), flow cytometry for M1/M2 polarization, cytokine assays Cellular and molecular life sciences Medium 41686220
2025 IFIT3 interacts with DVL2 (dishevelled 2) in the cytoplasm of lung squamous cell carcinoma cells and promotes phosphorylation of DVL2 at threonine 224, increasing phosphorylation of GSK-3β (S9) and β-catenin (S675), promoting β-catenin nuclear translocation and activating canonical WNT target genes (Cyclin D1, c-MYC, AXIN2). DVL2 knockdown or WNT inhibitor XAV-939 abrogated these effects. Co-immunoprecipitation (IFIT3/DVL isoforms), phosphorylation assays (T224-DVL2, S9-GSK3β, S675-β-catenin), β-catenin nuclear fractionation, luciferase reporter (TCF/β-catenin), siRNA knockdown of DVL2, XAV-939 pharmacological inhibition, in vivo tumor models The Journal of biological chemistry Medium 41850400
2024 IFIT3 promotes lymph node metastasis in esophageal squamous cell carcinoma by interacting with LASP1, facilitating LASP1 localization to the cell edge, promoting LASP1-Talin1 interaction and Talin1-integrin binding, and ultimately activating the FAK-ERK signaling pathway. Co-immunoprecipitation (IFIT3/LASP1/Talin1), confocal microscopy for subcellular localization, knockdown/overexpression, FAK-ERK phosphorylation assays, in vivo metastasis models Cell death & disease Medium 41413015
2024 IFIT3 selectively promotes M1 polarization of microglia and macrophages by activating STAT1 and NF-κB signaling pathways. Knockdown of IFIT3 inhibited M1 polarization without affecting M2 polarization, and ameliorated disease progression in EAE mice. siRNA knockdown, flow cytometry for M1/M2 markers, Western blot for pSTAT1 and NF-κB, AAV-mediated IFIT3 silencing in EAE mouse model International immunopharmacology Medium 38232539
2024 IFIT3 interacts with and modulates STAT1 in prostate cancer small extracellular vesicles (sEVs): loss of IFIT3 generates sEVs enriched in STAT1 while reducing cellular STAT1 levels, revealing a regulatory relationship between IFIT3 and STAT1 compartmentalization in intercellular communication. CRISPR/Cas9 knockdown of IFIT3, β6 integrin subunit, or STAT1; sEV isolation; Western blot for IFIT3 and STAT1 in cells and sEVs The Biochemical journal Low 34622927
2024 IFIT3 promotes the phosphorylation of TBK1 and STAT1 and upregulates IFN-β and ISG transcription during TGEV (porcine coronavirus) infection. Co-immunoprecipitation confirmed IFIT3 interaction with both TBK1 and STAT1; blocking the JAK-STAT1 pathway reversed IFIT3-mediated restriction of TGEV infection. Immunoprecipitation (IFIT3/TBK1 and IFIT3/STAT1), TBK1/STAT1 phosphorylation assays, overexpression/knockdown, JAK-STAT1 pathway inhibitor epistasis, viral replication assays Virology Medium 40381424
2023 SARS-CoV-2 NSP16 2'-O-methyltransferase activity protects viral mRNAs from restriction by IFIT1 and IFIT3. Silencing either IFIT1 or IFIT3 partially restored fitness to the NSP16-deficient SARS-CoV-2 mutant, demonstrating that IFIT3 senses the absence of 2'-O-methylation on viral RNA caps. SARS-CoV-2 NSP16 active-site mutation, siRNA knockdown of IFIT1/IFIT3, viral replication assays in vitro, hamster model in vivo, IFN-I sensitivity assays, sinefungin (MTase inhibitor) treatment Journal of virology High 36722972
2010 IFIT3 (the most upregulated gene under antiviral conditions in Daudi cells) contributes to IFN-α antiviral activity: IFIT3-siRNA knockdown reduced IFN-α-induced antiviral protection, and IFIT3 overexpression decreased viral titers. siRNA knockdown, overexpression, antiviral assay (viral titer measurement), antibody neutralization, microarray analysis Journal of virology Low 20686046

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. Journal of immunology (Baltimore, Md. : 1950) 146 21813773
2018 Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability. Immunity 106 29525521
2006 RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins. Proceedings of the National Academy of Sciences of the United States of America 101 17050680
2018 IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA. Nucleic acids research 90 29554348
2019 IFIT1 and IFIT3 promote oral squamous cell carcinoma metastasis and contribute to the anti-tumor effect of gefitinib via enhancing p-EGFR recycling. Oncogene 84 30626937
2018 Association of Abnormal Elevations in IFIT3 With Overactive Cyclic GMP-AMP Synthase/Stimulator of Interferon Genes Signaling in Human Systemic Lupus Erythematosus Monocytes. Arthritis & rheumatology (Hoboken, N.J.) 81 29806091
2013 Protective roles of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in dengue virus infection of human lung epithelial cells. PloS one 75 24223959
1997 Cloning of a gene (RIG-G) associated with retinoic acid-induced differentiation of acute promyelocytic leukemia cells and representing a new member of a family of interferon-stimulated genes. Proceedings of the National Academy of Sciences of the United States of America 70 9207104
2010 Identification of alpha interferon-induced genes associated with antiviral activity in Daudi cells and characterization of IFIT3 as a novel antiviral gene. Journal of virology 68 20686046
2017 Hepatic IFIT3 predicts interferon-α therapeutic response in patients of hepatocellular carcinoma. Hepatology (Baltimore, Md.) 65 28295457
1996 The glucocorticoid attenuated response genes GARG-16, GARG-39, and GARG-49/IRG2 encode inducible proteins containing multiple tetratricopeptide repeat domains. Archives of biochemistry and biophysics 57 8660659
2020 Inflammatory IFIT3 renders chemotherapy resistance by regulating post-translational modification of VDAC2 in pancreatic cancer. Theranostics 53 32641986
1998 IFI60/ISG60/IFIT4, a new member of the human IFI54/IFIT2 family of interferon-stimulated genes. Genomics 53 9828129
2016 Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a. Scientific reports 44 27210312
2016 Herpes Simplex Virus 1 Tegument Protein UL41 Counteracts IFIT3 Antiviral Innate Immunity. Journal of virology 40 27681138
2023 SARS-CoV-2 Uses Nonstructural Protein 16 To Evade Restriction by IFIT1 and IFIT3. Journal of virology 39 36722972
2022 The emerging roles of IFIT3 in antiviral innate immunity and cellular biology. Journal of medical virology 39 36305096
2013 Poly(I:C) inhibits porcine reproductive and respiratory syndrome virus replication in MARC-145 cells via activation of IFIT3. Antiviral research 39 23791982
2016 Injectable hyaluronic acid down-regulates interferon signaling molecules, IGFBP3 and IFIT3 in the bovine intervertebral disc. Acta biomaterialia 32 28003146
2015 Overexpression of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in pancreatic cancer: cellular "pseudoinflammation" contributing to an aggressive phenotype. Oncotarget 30 25650658
2019 NF-κB-Dependent IFIT3 Induction by HBx Promotes Hepatitis B Virus Replication. Frontiers in microbiology 23 31681236
2011 Label-free quantitative proteomics reveals regulation of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and 5'-3'-exoribonuclease 2 (XRN2) during respiratory syncytial virus infection. Virology journal 22 21933386
2022 COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation. Frontiers in oncology 18 35280763
2021 Murine Ifit3 restricts the replication of Rabies virus both in vitro and in vivo. The Journal of general virology 18 34269675
2022 IFIT3 Is Increased in Serum from Patients with Chronic Hepatitis B Virus (HBV) Infection and Promotes the Anti-HBV Effect of Interferon Alpha via JAK-STAT2 In Vitro. Microbiology spectrum 17 36314949
2022 IFIT3 mediated the type I interferon antiviral response by targeting Senecavirus A entry, assembly and release pathways. Veterinary microbiology 17 36332300
2018 A Talented Duo: IFIT1 and IFIT3 Patrol Viral RNA Caps. Immunity 17 29562196
2017 Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease. BMC cancer 16 28356064
2022 LncRNA RP5-998N21.4 promotes immune defense through upregulation of IFIT2 and IFIT3 in schizophrenia. Schizophrenia (Heidelberg, Germany) 14 35232977
2022 IFIT3 and IFIT5 Play Potential Roles in Innate Immune Response of Porcine Pulmonary Microvascular Endothelial Cells to Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus. Viruses 14 36146725
2020 Novel evidence for retinoic acid-induced G (Rig-G) as a tumor suppressor by activating p53 signaling pathway in lung cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 32741018
2025 IFIT3: a crucial mediator in innate immunity and tumor progression with therapeutic implications. Frontiers in immunology 13 40061935
2024 Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3. Journal of virology 12 38289117
2024 Induction of IFIT1/IFIT3 and inhibition of Bcl-2 orchestrate the treatment of myeloma and leukemia via pyroptosis. Cancer letters 12 38462032
2023 UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma. Cell death & disease 12 38129382
2018 Down-regulation of IFIT3 protects liver from ischemia-reperfusion injury. International immunopharmacology 12 29734133
2016 Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB. Oncotarget 12 27602766
2021 IFIT3 (interferon induced protein with tetratricopeptide repeats 3) modulates STAT1 expression in small extracellular vesicles. The Biochemical journal 11 34622927
2013 Rig-G negatively regulates SCF-E3 ligase activities by disrupting the assembly of COP9 signalosome complex. Biochemical and biophysical research communications 11 23415865
2023 Differential expression of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in Alzheimer's disease and HIV-1 associated neurocognitive disorders. Scientific reports 10 36841839
2023 IFIT3 inhibits Epstein-Barr virus reactivation via upregulating innate immunity. Journal of medical virology 10 37994186
2024 Knockdown of IFIT3 ameliorates multiple sclerosis via selectively regulating M1 polarization of microglia in an experimental autoimmune encephalomyelitis model. International immunopharmacology 9 38232539
2023 Lysyl oxidase-like 2 promotes stemness and enhances antitumor effects of gefitinib in head and neck cancer via IFIT1 and IFIT3. Cancer science 9 37496288
2010 Intact JAK-STAT signaling pathway is a prerequisite for STAT1 to reinforce the expression of RIG-G gene. Experimental cell research 8 21056555
2025 The IFIT2-IFIT3 antiviral complex targets short 5' untranslated regions on viral mRNAs for translation inhibition. Nature microbiology 7 41093992
2024 Circ_BBS9 as an early diagnostic biomarker for lung adenocarcinoma: direct interaction with IFIT3 in the modulation of tumor immune microenvironment. Frontiers in immunology 7 39139574
2018 Interferon-stimulated gene 60 (ISG60) constitutes a negative feedback loop in the downstream of TLR3 signaling in hCMEC/D3 cells. Journal of neuroimmunology 7 30195920
2010 PU.1 directly regulates retinoic acid-induced expression of RIG-G in leukemia cells. FEBS letters 7 21176776
2025 IFIT3 RNA-binding activity promotes influenza A virus infection and translation efficiency. Journal of virology 6 40497724
2024 IFIT3 accelerates the progression of head and neck squamous cell carcinoma by targeting PD-L1 to activate PI3K/AKT signaling pathway. World journal of surgical oncology 6 38273364
2022 Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active Tuberculosis from Latent Infection. Current medical science 6 36462134
2021 Retinoic Acid-Induced Gene G(RIG-G) as a Novel Monitoring Biomarker in Leukemia and Its Clinical Applications. Genes 6 34356051
2025 FAM210B activates STAT1/IRF9/IFIT3 axis by upregulating IFN-α/β expression to impede the progression of lung adenocarcinoma. Cell death & disease 5 39900908
2024 ETV7 promotes colorectal cancer progression through upregulation of IFIT3. Functional & integrative genomics 5 38200280
2024 IFIT3 mediates TBK1 phosphorylation to promote activation of pDCs and exacerbate systemic sclerosis in mice. Clinical and translational medicine 4 39305055
2015 RIG-G inhibits the proliferation of NB4 cells and propels ATRA-induced differentiation of APL cells. Leukemia research 4 26686474
2025 IFIT3 inhibits transmissible gastroenteritis virus (TGEV) infection by promoting the phosphorylation of TBK1 and STAT1, which enhances the innate immune response. Virology 3 40381424
2024 diABZI and poly(I:C) inhibit osteoclastic bone resorption by inducing IRF7 and IFIT3. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 3 38874138
2024 Expression of ISG60 is induced by TLR3 signaling in BEAS‑2B bronchial epithelial cells: Possible involvement in CXCL10 expression. Molecular medicine reports 3 38963029
2024 Unraveling the roles of IFIT3 gene and immune-metabolic pathways in psoriasis: a bioinformatics exploration for diagnostic markers and therapeutic targets. Frontiers in molecular biosciences 3 39239353
2024 Potential protective role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in COVID-19. Frontiers in cellular and infection microbiology 3 39664492
2023 NMI promotes tumor progression and gemcitabine resistance in pancreatic cancer via STAT3-IFIT3 axis. Molecular carcinogenesis 3 37846815
2012 [Role of auto-secreted interferon α in all-trans retinoic acid-induced expression of RIG-G gene]. Zhonghua yi xue za zhi 3 22490698
2025 Silencing IFIT3 suppresses the EGFR/VEGF pathway and modulates SOCS1 to attenuate skin fibrosis in systemic sclerosis. Apoptosis : an international journal on programmed cell death 2 40515878
2024 WGCNA and machine learning analysis identifi ed SAMD9 and IFIT3 as primary Sjögren's Syndrome key genes. Heliyon 2 38707449
2026 IFIT3 stabilizes STING via USP18 to drive M1 macrophage polarization and early inflammation in acute lung injury. Cellular and molecular life sciences : CMLS 1 41686220
2025 Short 5' UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex. bioRxiv : the preprint server for biology 1 39990370
2025 IFIT3 activation significantly contributes to HIV-1-associated neurodegenerative disorder-mediated neuroinflammation. Frontiers in immunology 1 40936921
2025 Downregulation of IFIT3 Relieves the Inflammatory Response in Ulcerative Colitis via Selectively Regulating Macrophage M1 Polarization and the STAT1/2 Signaling Pathway. Journal of inflammation research 1 40951449
2022 SARS-CoV-2 Uses Nonstructural Protein 16 to Evade Restriction by IFIT1 and IFIT3. bioRxiv : the preprint server for biology 1 36203546
2026 Interferon-induced protein IFIT3 as a molecular nexus of neuroinflammation in Alzheimer's disease and HIV-associated neurocognitive disorders. Journal of neuroinflammation 0 41772634
2026 IFIT3-DVL interaction promotes malignant progression of lung squamous cell carcinoma and large-cell lung carcinoma via canonical WNT signaling. The Journal of biological chemistry 0 41850400
2026 Repetitive transcranial magnetic stimulation modulates neuroinflammation and cell apoptosis via the interaction between Ifit3 and Stat1 for the treatment of neuropathic pain. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 0 41865234
2026 IFIT3 Associates with m⁶A-Modified RNA to Restrict Hepatitis C Virus Infection. bioRxiv : the preprint server for biology 0 41929069
2025 IFIT3 RNA-binding activity promotes influenza A virus infection and translation efficiency. bioRxiv : the preprint server for biology 0 40027740
2025 IFI35 and IFIT3 are potentially important biomarkers for early diagnosis and treatment of esophageal squamous cell carcinoma: based on WGCNA and machine learning analysis. Frontiers in genetics 0 40463715
2025 A Potential CD8+ T-Cell-Related Biomarker IFIT3 for Rheumatoid Arthritis. International journal of rheumatic diseases 0 40801343
2025 IFIT3 promotes lymph node metastasis by interacting with LASP1 to activate FAK-ERK signaling in esophageal squamous cell carcinoma. Cell death & disease 0 41413015
2025 HERC5, IFI6, IFIT3, and OASL as potential diagnostic biomarkers for systemic lupus erythematosus: an integrated bioinformatics, machine learning and clinical validation. Clinical rheumatology 0 41432807
2007 [Study on mechanisms of the expression regulation of interferon-induced gene RIG-G]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 18067071
2007 [Utilization of the stable ectopic expression cell line as a model for the investigation of RIG-G gene]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 0 18476588

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