Affinage

TRIM14

Tripartite motif-containing protein 14 · UniProt Q14142

Length
442 aa
Mass
49.8 kDa
Annotated
2026-06-10
70 papers in source corpus 27 papers cited in narrative 27 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

TRIM14 is a mitochondrial outer-membrane scaffold protein that integrates innate antiviral and inflammatory signaling and, in cancer contexts, stabilizes a broad set of substrate proteins by controlling their ubiquitination-dependent turnover (PMID:24379373, PMID:27666593). In RNA-virus sensing, it docks at MAVS, undergoes K63-linked polyubiquitination at Lys365, and recruits NEMO to the MAVS signalosome to drive IRF3 and NF-κB activation (PMID:24379373); it further serves as a mitochondrial platform for a WHIP–TRIM14–PPP6C complex that optimizes RIG-I localization and activation (PMID:29053956). A recurrent mechanism is the recruitment of the deubiquitinase USP14 (and BRCC3) to remove K48- or K63-linked ubiquitin chains from client proteins, sparing them from p62- or OPTN-mediated selective autophagic degradation: this axis stabilizes cGAS to support DNA-virus antiviral responses (PMID:27666593), sustains noncanonical NF-κB by protecting p100/p52 (PMID:31921549), preserves KDM4D to maintain H3K9 demethylation and proinflammatory IL-12/IL-23 expression in dendritic cells (PMID:35145029), and stabilizes the immune checkpoint ligand PD-L1 to suppress CD8+ T-cell antitumor activity (PMID:38924473). Conversely, through its C-terminal PRYSPRY/SPRY domain—whose basic surface mediates interactions with acidic targets (PMID:30973643)—TRIM14 restricts viral replication by directing K48-linked ubiquitination and proteasomal degradation of viral proteins including HCV NS5A, HBx, influenza A NP, and TMUV NS1 (PMID:27578425, PMID:30150992, PMID:30873142, PMID:40435148). TRIM14 also directly promotes K63-ubiquitination of TBK1 to enhance IFN-β production (PMID:40435148) and acts as a TBK1–STAT3 scaffold that resolves type I IFN signaling via Ser727-STAT3 phosphorylation and SOCS3 induction during M. tuberculosis infection (PMID:32404352). TRIM14 expression is itself an interferon- and inflammation-responsive node, transcriptionally activated by IRF-1/IRF-2 and STAT1 through promoter ISRE/GC elements (PMID:30150992, PMID:31150153). In tumor and inflammatory tissues it activates NF-κB by binding NEMO or promoting IκBα degradation (PMID:31070748, PMID:41250673) and stabilizes oncogenic effectors, while its own level is restrained by RNF125-mediated K48-ubiquitination and proteasomal degradation (PMID:28476934).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2013 High

    Established the founding mechanism by placing TRIM14 on mitochondria as a MAVS-associated scaffold that recruits NEMO, defining how a RING-less TRIM links the antiviral sensor platform to downstream IRF3/NF-κB activation.

    Evidence Co-IP, mitochondrial fractionation, K365 ubiquitination mutagenesis, and siRNA knockdown with reporter readouts

    PMID:24379373

    Open questions at the time
    • E3 ligase responsible for K365 K63-ubiquitination of TRIM14 not identified here
    • Stoichiometry and architecture of the MAVS–TRIM14–NEMO signalosome unresolved
  2. 2016 High

    Defined TRIM14's stabilizing arm by showing it recruits USP14 to deubiquitinate cGAS and block its autophagic degradation, explaining how TRIM14 supports DNA-virus sensing in vivo.

    Evidence Co-IP, Trim14 KO mice with HSV-1 challenge, in vitro DUB assay, autophagy flux, K414 mutagenesis

    PMID:27666593

    Open questions at the time
    • How TRIM14 selects USP14 over other DUBs not addressed
    • Whether mitochondrial localization is required for cGAS stabilization unclear
  3. 2016 High

    Showed TRIM14 can act directly against viral proteins, with its SPRY domain targeting HCV NS5A for K48-ubiquitination and degradation independently of IFN/NF-κB, distinguishing a degradative restriction activity from its scaffolding role.

    Evidence Domain-deletion mapping, Co-IP, ubiquitination and viral replication assays in KO/overexpression systems

    PMID:27578425

    Open questions at the time
    • TRIM14 lacks a RING domain, so the E3 ligase executing K48-ubiquitination of NS5A is not defined
    • Direct vs. adaptor role in NS5A ubiquitination unresolved
  4. 2017 High

    Extended the mitochondrial scaffold concept by defining a WHIP–TRIM14–PPP6C ternary complex that optimizes RIG-I activation, showing TRIM14 organizes multiple signalosome components rather than acting alone.

    Evidence Pooled RNAi screen, yeast two-hybrid, reciprocal Co-IP, domain mapping, in vitro dephosphorylation assay

    PMID:29053956

    Open questions at the time
    • Direct TRIM14 contacts within the complex not atomically mapped
    • Relationship between this complex and the MAVS–NEMO axis not integrated
  5. 2017 High

    Identified RNF125 as the negative regulator that limits TRIM14 abundance via K48-ubiquitination and proteasomal degradation, establishing how TRIM14-driven antiviral signaling is turned down.

    Evidence Reciprocal Co-IP, in cellulo ubiquitination assay, RNF125-deficient MEFs

    PMID:28476934

    Open questions at the time
    • Signal that triggers RNF125-mediated turnover of TRIM14 unknown
    • Whether RNF125 acts on the mitochondrial pool specifically not determined
  6. 2018 Medium

    Placed TRIM14 as an interferon-stimulated gene driven by STAT1 and showed SPRY-mediated targeting of HBx, broadening the viral-restriction repertoire and linking TRIM14 induction to IFN-I.

    Evidence Promoter-binding/reporter assays, Co-IP domain mapping, viral replication assays

    PMID:30150992

    Open questions at the time
    • Direct STAT1 promoter occupancy shown by reporter-equivalent rather than full ChIP
    • Mechanistic detail of HBx complex disruption inferred ('potentially')
  7. 2019 High

    Generalized the TRIM14–USP14 deubiquitination axis to noncanonical NF-κB by showing it protects p100/p52 from autophagic degradation, connecting TRIM14 to inflammatory tissue responses.

    Evidence Co-IP, K63 chain characterization, Trim14 KO mice, autophagy flux, colitis/tumor models

    PMID:31921549

    Open questions at the time
    • Subcellular site of p100/p52 stabilization not specified
    • Whether the same complex operates in non-immune cells unaddressed
  8. 2019 High

    Provided atomic-level basis for TRIM14 target selection by solving the PRYSPRY structure and showing its basic surface binds acidic peptides, rationalizing its broad protein-interaction profile.

    Evidence X-ray crystallography and isothermal titration calorimetry

    PMID:30973643

    Open questions at the time
    • No co-structure with a physiological partner
    • Does not explain how the same surface achieves stabilizing vs. degradative outcomes
  9. 2019 High

    Demonstrated domain-dependent dual control of a viral substrate, with PRYSPRY driving influenza NP degradation and a ΔS2 region stabilizing it, showing TRIM14 outputs are tunable by its own domains.

    Evidence Co-IP, domain-deletion mapping, ubiquitination assays, NP nuclear translocation imaging

    PMID:30873142

    Open questions at the time
    • E3 ligase mediating NP K48-ubiquitination not identified
    • Physiological balance between the two domain activities in infection unclear
  10. 2019 Medium

    Defined a positive feedback loop in endothelium where TRIM14 binds NEMO to drive IκBα/p65 phosphorylation and p65 in turn induces TRIM14, linking TRIM14 to TNF-α-driven NF-κB amplification.

    Evidence Co-IP, promoter ChIP, ubiquitination assays in overexpression/knockdown cells

    PMID:31070748

    Open questions at the time
    • Single-lab evidence for the feedback loop
    • Direct vs. scaffold-mediated NEMO activation not separated
  11. 2019 Medium

    Opened the oncogenic dimension by showing TRIM14 stabilizes pro-tumor effectors (ZEB2, Dvl2) and degrades tumor suppressor PTEN to drive proliferation, EMT, chemoresistance, and AKT activation.

    Evidence Knockdown/overexpression, ubiquitination and cycloheximide-chase stability assays, epistasis rescue, in vitro/in vivo tumor models

    PMID:29867201 PMID:30728039 PMID:31296997

    Open questions at the time
    • Whether TRIM14 directly ubiquitinates these substrates or acts via recruited enzymes unresolved
    • Cell-type specificity of opposing stabilizing/degradative outcomes unexplained
  12. 2020 High

    Revealed a negative-regulatory scaffolding role in which TRIM14 bridges cGAS/TBK1 to STAT3 and promotes Ser727-STAT3 phosphorylation and SOCS3 to dampen type I IFN, showing TRIM14 can resolve as well as initiate IFN responses.

    Evidence Trim14 KO macrophages, Co-IP for cGAS and TBK1, phospho-specific blots, M. tuberculosis replication assays

    PMID:32404352

    Open questions at the time
    • How TRIM14 switches between IFN-promoting and IFN-resolving modes unclear
    • Determinants of Ser727 vs Ser754 selectivity not defined
  13. 2022 High

    Showed TRIM14 builds a USP14/BRCC3 deubiquitinase complex to protect KDM4D from OPTN-mediated autophagy, linking TRIM14 to epigenetic (H3K9) control of proinflammatory cytokine expression in dendritic cells.

    Evidence Co-IP, K63 ubiquitination assays, autophagy flux, KO dendritic cells, histone methylation assays, autoimmune model

    PMID:35145029

    Open questions at the time
    • Respective contributions of USP14 vs BRCC3 not dissected
    • Whether KDM4D stabilization occurs at chromatin or in cytoplasm unclear
  14. 2023 Medium

    Extended viral targeting to filoviruses, showing TRIM14 binds EBOV nucleoprotein, enhances IFN-β/NF-κB promoter activation, and restricts replication in vivo.

    Evidence Co-IP, IFN-β/NF-κB reporter assays, viral replication assay, TRIM14 KO mice

    PMID:37562033

    Open questions at the time
    • Whether NP is degraded or merely sensed not resolved
    • Direct molecular consequence of the TRIM14–NP interaction undefined
  15. 2024 High

    Connected the TRIM14–USP14 stabilization axis to tumor immune evasion by showing IFNα-induced TRIM14 protects PD-L1 from autophagy, providing a pharmacological combination (IU1 + IFNα + anti-CTLA4) rationale.

    Evidence Co-IP, K63 ubiquitination assays, autophagy flux, KO/knockdown, CD8+ T-cell assays, in vivo tumor models with USP14 inhibitor

    PMID:38924473

    Open questions at the time
    • Generality across tumor types beyond models tested unknown
    • How IFNα simultaneously induces TRIM14 and PD-L1 not fully integrated
  16. 2024 Medium

    Added tumor-suppressive substrate degradation, with TRIM14 binding and degrading GFAT1 to reduce hexosamine flux and O-glycosylation in NSCLC, and revealed TCF19 as an additional transcriptional driver of the TRIM14–TBK1–IFN-β axis.

    Evidence Co-IP, ubiquitination assays, metabolic rescue with N-acetyl-glucosamine, tumor assays; separate ChIP/promoter, humanized mouse, and CD8+ T-cell exhaustion assays

    PMID:37566545 PMID:38267812

    Open questions at the time
    • Opposing pro- and anti-tumor roles across studies not reconciled
    • Direct E3 activity vs adaptor function for GFAT1 degradation unresolved
  17. 2025 High

    Consolidated TRIM14 as a TBK1 K63-ubiquitin enhancer and viral-protein degrader in the duck TMUV system, mapping specific ubiquitination sites on both TBK1 and viral NS1.

    Evidence Co-IP, site-specific mutagenesis (TBK1 K30/K401, NS1 K141), viral replication assays, in vivo duck infection

    PMID:40435148

    Open questions at the time
    • Whether TRIM14 directly catalyzes TBK1 K63 chains given absence of a RING domain unclear
    • Conservation of these sites in mammalian TBK1 not addressed
  18. 2025 High

    Broadened the stabilizing axis to redox control, showing a radiation-induced TRIM14/USP14 complex removes K48 chains from GPX4 to suppress ferroptosis, with USP14 inhibition radiosensitizing HCC.

    Evidence CRISPR DUB screen, Co-IP, K48/K118 site mutagenesis, ferroptosis assays, PDX models

    PMID:40595451

    Open questions at the time
    • Mechanism recruiting TRIM14 to the GPX4 locus after radiation unclear
    • Whether ferroptosis control is mitochondrial or cytosolic unresolved
  19. 2025 Medium

    Linked TRIM14 to tissue inflammation, driving NF-κB via IκBα degradation in microglia (neuroinflammation/pyroptosis) and via TRAF3 autophagic degradation in keratinocytes (psoriasis), reinforcing its proinflammatory scaffolding role across disease contexts.

    Evidence Knockdown/overexpression, ubiquitination and autophagy assays, AAV-CRISPR rat SCI model and psoriatic mouse model

    PMID:39933682 PMID:41250673

    Open questions at the time
    • Single-lab, single-model evidence for each disease context
    • Direct vs indirect control of IκBα ubiquitination not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a RING-less TRIM14 directs both K48/K63 substrate ubiquitination and DUB recruitment — i.e., which partner E3 ligases it co-opts and how the same PRYSPRY surface produces opposite stabilizing vs degradative outcomes — remains unresolved.
  • No catalytic E3 partner defined for TRIM14-mediated K48/K63 ubiquitination
  • No structural basis for the switch between substrate stabilization and degradation
  • Determinants of cell-type-specific antiviral vs pro-tumor outputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 5 R-HSA-9612973 Autophagy 5 R-HSA-162582 Signal Transduction 3
Partners
BRCC3CGASMAVSNEMO/IKBKGPPP6CSTAT3TBK1USP14
Complex memberships
MAVS signalosomeTRIM14-USP14-BRCC3 deubiquitinase complexWHIP-TRIM14-PPP6C complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 TRIM14 localizes to the outer membrane of mitochondria and interacts with MAVS. Upon viral infection, TRIM14 undergoes Lys-63-linked polyubiquitination at Lys-365 and recruits NF-κB essential modulator (NEMO) to the MAVS signalosome, leading to activation of both the IRF3 and NF-κB pathways. Knockdown of TRIM14 disrupts the NEMO-MAVS association and attenuates the antiviral response. Co-immunoprecipitation, subcellular fractionation/mitochondria localization, knockdown (siRNA), site-directed mutagenesis (K365 ubiquitination), reporter assays Proceedings of the National Academy of Sciences of the United States of America High 24379373
2016 TRIM14 stabilizes cGAS by recruiting the deubiquitinase USP14, which cleaves K48-linked ubiquitin chains from cGAS at lysine 414, preventing p62-dependent selective autophagic degradation of cGAS. TRIM14 knockout impairs HSV-1-triggered antiviral responses and Trim14−/− mice are highly susceptible to lethal HSV-1 infection. Co-immunoprecipitation, knockout mice, ubiquitination assays, in vitro deubiquitination assay, autophagy flux assays, site-directed mutagenesis (K414) Molecular cell High 27666593
2016 TRIM14 inhibits HCV replication through its C-terminal SPRY domain, which interacts with the HCV NS5A protein (specifically the NS5A1 subdomain) and induces its K48-linked ubiquitination and degradation, independently of NF-κB or IFN pathway activation. Overexpression, knockout, domain-deletion mapping, co-immunoprecipitation, ubiquitination assays, viral replication assays Scientific reports High 27578425
2017 TRIM14 acts as a mitochondrial docking platform for assembly of a WHIP-TRIM14-PPP6C complex that promotes RIG-I mitochondrial localization and optimal activation. WHIP bridges RIG-I with MAVS via its ubiquitin-binding domain interacting with polyUb chains on RIG-I at K164, and PPP6C dephosphorylates RIG-I. The ATPase domain of WHIP stabilizes the RIG-I–dsRNA interaction. Pooled RNAi screen, yeast two-hybrid, co-immunoprecipitation, domain-deletion mapping, in vitro dephosphorylation assay Molecular cell High 29053956
2017 RNF125 functions as an E3 ubiquitin ligase that interacts with TRIM14, catalyzes K48-linked polyubiquitination of TRIM14, and promotes its proteasomal degradation, thereby acting as a negative regulator of TRIM14-mediated innate antiviral signaling. RNF125-deficient MEFs retain TRIM14 protein at late time points of viral infection. Co-immunoprecipitation, ubiquitination assays, overexpression, knockdown, RNF125-deficient MEFs Journal of immunology High 28476934
2018 TRIM14 inhibits HBV replication as an IFN-I-stimulated gene (ISG) whose transcription is directly activated by STAT1 (but not STAT3) binding to the TRIM14 promoter. The TRIM14 SPRY domain interacts with the C-terminal domain of HBx, potentially blocking HBx-facilitated formation of the Smc-HBx-DDB1 complex required for HBV replication. Reporter assays (ChIP-equivalent promoter binding), co-immunoprecipitation, domain mapping, overexpression, knockdown, viral replication assays Frontiers in immunology Medium 30150992
2019 TRIM14 promotes noncanonical NF-κB signaling by recruiting deubiquitinase USP14 to cleave K63-linked ubiquitin chains from p100/p52 at multiple sites, thereby preventing p62-mediated selective autophagic degradation of p100/p52 and sustaining noncanonical NF-κB activation. Trim14-deficient mice show impaired noncanonical NF-κB-mediated inflammatory responses. Co-immunoprecipitation, ubiquitination assays, knockout mice, autophagy flux assays, in vivo colitis/tumor models Advanced science High 31921549
2019 The crystal structure of the TRIM14 PRYSPRY domain reveals a positively charged (basic) surface that mediates protein-protein interactions preferentially with acidic amino acid residues, as validated by isothermal titration calorimetry showing binding of the domain to acidic peptides. X-ray crystallography, isothermal titration calorimetry (ITC) FEBS letters High 30973643
2019 TRIM14 interacts with the viral nucleoprotein (NP) of Influenza A virus through multiple domains: the PRYSPRY domain promotes K48-linked ubiquitination and proteasomal degradation of NP (inhibiting viral RNP formation and NP nuclear translocation), while the ΔS2 domain antagonizes this by stabilizing NP. TRIM14 restricts IAV replication in an IFN/NF-κB-independent manner. Co-immunoprecipitation, domain-deletion mapping, ubiquitination assays, viral replication assays, NP nuclear translocation imaging Frontiers in microbiology High 30873142
2019 TRIM14 promotes NF-κB activation in vascular endothelial cells by directly binding to NEMO (IKK complex) upon TNF-α stimulation, promoting IκBα and p65 phosphorylation in a manner dependent on K63-linked ubiquitination of TRIM14. p65 in turn binds directly to the TRIM14 promoter to enhance TRIM14 transcription, forming a positive feedback loop. Co-immunoprecipitation, promoter ChIP (p65 binding to TRIM14 promoter), ubiquitination assays, overexpression, knockdown Journal of molecular cell biology Medium 31070748
2019 TRIM14 inactivation in glioblastoma cells causes ubiquitination and proteasomal degradation of ZEB2, a transcription factor involved in EMT, indicating that TRIM14 stabilizes ZEB2 by preventing its ubiquitination. Knockdown (shRNA), ubiquitination assays, cycloheximide chase (stability analysis), western blot Journal of experimental & clinical cancer research Medium 30728039
2019 IRF-1 and IRF-2 bind to the TRIM14 promoter (at a GC box and ISRE element) and activate TRIM14 transcription; IRF-1 mediates IFN-α-induced upregulation of TRIM14, while IRF-2 is required for basal TRIM14 transcription. Knockdown of IRF-1 reduces IFN-α-stimulated TRIM14 expression. Promoter reporter assays, EMSA/ChIP (IRF binding to TRIM14 promoter), siRNA knockdown, RT-PCR FEBS open bio Medium 31150153
2018 TRIM14 stabilizes Dishevelled 2 (Dvl2) protein in glioma cells, activating canonical Wnt/β-catenin signaling and promoting chemoresistance to temozolomide. Inhibition of Dvl2 reverses the oncogenic effects of TRIM14 overexpression on chemoresistance. Overexpression, knockdown, western blot (Dvl2 stability), in vitro and in vivo TMZ resistance assays, pharmacological inhibition of Dvl2 Oncogene Medium 29867201
2019 TRIM14 co-localizes with PTEN in the cytoplasm and induces PTEN ubiquitination, leading to PTEN degradation and downstream AKT pathway activation to promote colorectal cancer cell proliferation. Co-immunoprecipitation/co-localization, ubiquitination assay, western blot, overexpression/knockdown, epistasis via PTEN overexpression rescue Cancer management and research Medium 31296997
2019 TRIM14 interacts with PPM1A and mediates its ubiquitination in human nucleus pulposus cells, promoting NF-κB p65 activation and TNF-α-induced apoptosis. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown, western blot Artificial cells, nanomedicine, and biotechnology Low 31322007
2020 In Mycobacterium tuberculosis-infected macrophages, TRIM14 acts as a negative regulator of type I IFN responses by interacting with both cGAS and TBK1, acting as a scaffold to promote STAT3 phosphorylation at Ser727 (over Ser754), thereby upregulating SOCS3 to resolve IFN signaling. Trim14 KO macrophages hyperinduce ISG expression and are better at restricting M. tuberculosis replication. Knockout macrophages, co-immunoprecipitation (cGAS and TBK1 interaction), phospho-specific western blot, cytokine/ISG measurement, bacterial colony assays Journal of immunology High 32404352
2022 TRIM14 recruits deubiquitinases USP14 and BRCC3 to form a regulatory complex that cleaves K63-linked ubiquitin chains from the histone demethylase KDM4D, thereby preventing OPTN (optineurin)-mediated selective autophagic degradation of KDM4D. This preserves KDM4D-mediated inhibition of histone H3K9 trimethylation, epigenetically promoting IL-12 and IL-23 expression in dendritic cells. TRIM14 deficiency in dendritic cells impairs proinflammatory cytokine expression and protects mice from autoimmune inflammation. Co-immunoprecipitation, ubiquitination assays, autophagy flux assays, KO dendritic cells, histone methylation assays, in vivo autoimmune model Proceedings of the National Academy of Sciences of the United States of America High 35145029
2024 TRIM14 recruits USP14 to inhibit autophagic degradation of PD-L1 by removing K63-linked ubiquitin chains from PD-L1, impairing recognition of PD-L1 by the cargo receptor p62 for autophagic degradation. IFNα transcriptionally upregulates TRIM14, which then stabilizes PD-L1 and suppresses CD8+ T cell-mediated antitumor activity. Combining USP14 inhibitor IU1 with IFNα and anti-CTLA4 effectively suppresses tumor growth. Co-immunoprecipitation, ubiquitination assays (K63 chain type), autophagy flux assays, KO/knockdown, CD8+ T cell functional assays, in vivo tumor models Cancer research High 38924473
2025 TRIM14 assembles at the GPX4 locus following radiation and recruits USP14, forming a TRIM14/USP14 complex that removes K48-linked polyubiquitination from GPX4 at K48 or K118, thereby stabilizing GPX4 and suppressing radiation-induced ferroptosis. Pharmacological inhibition of USP14 sensitizes HCC to radiotherapy. CRISPR-based DUB screen, co-immunoprecipitation, ubiquitination site mapping (K48/K118 mutagenesis), in vitro ferroptosis assays, patient-derived xenograft models Cell death & disease High 40595451
2025 TRIM14 interacts with duck TBK1 and promotes its K63-linked polyubiquitination on K30 and K401, augmenting IFN-β production during TMUV infection. Separately, TRIM14 interacts with TMUV NS1 protein, facilitating K27/K29-linked polyubiquitination of NS1 and its proteasomal degradation; K141 on NS1 is critical for this process. Co-immunoprecipitation, ubiquitination site mapping (mutagenesis of TBK1 K30/K401 and NS1 K141), in vitro viral replication assays, in vivo (duck) infection model PLoS pathogens High 40435148
2025 TRIM14 promotes IκBα ubiquitination and degradation in spinal cord microglia, thereby activating NF-κB and driving M1 polarization and NLRP3-mediated pyroptosis. TRIM14 knockdown stabilizes IκBα, suppresses NF-κB/NLRP3 signaling, attenuates neuroinflammation, and improves locomotor recovery in rats after spinal cord injury. Knockdown/overexpression, ubiquitination assay (IκBα), western blot (phospho-NF-κB), AAV-CRISPR in vivo, rat SCI model Mediators of inflammation Medium 41250673
2024 TRIM14 directly binds to GFAT1 (glutamine fructose-6-phosphate amidotransferase 1), a rate-limiting enzyme of the hexosamine biosynthetic pathway, and promotes its ubiquitination and degradation, reducing O-glycosylation and suppressing NSCLC cell proliferation and migration. N-acetyl-D-glucosamine supplementation rescues the inhibitory effect. Co-immunoprecipitation, ubiquitination assay, rescue experiment (N-acetyl-glucosamine), knockdown/overexpression, in vitro and in vivo tumor assays Carcinogenesis Medium 38267812
2024 TCF19 transcriptionally promotes TRIM14 expression, and the TCF19-TRIM14 axis activates TBK1-IRF3-IFN-β signaling; enhanced IFN-β secretion facilitates CD8+ T cell exhaustion via differentiation reprogramming in MSI endometrial cancer. ChIP/promoter analysis (TCF19 binding to TRIM14 promoter), overexpression/knockdown, IFN-β ELISA, humanized mouse models, CD8+ T cell functional assays Cell reports Medium 37566545
2025 TRIM14 binds to TRAF3 and mediates its autophagic degradation via the selective autophagy receptor NDP52, activating the NF-κB pathway and driving psoriasis-associated keratinocyte proliferation and inflammation. Co-immunoprecipitation (TRIM14-TRAF3 and TRIM14-NDP52 interactions), autophagy flux assays, overexpression/knockdown, in vivo psoriatic mouse model International journal of biological macromolecules Medium 39933682
2023 TRIM14 interacts with EBOV nucleoprotein, and this interaction enhances IFN-β and NF-κB promoter activation. TRIM14 overexpression reduces EBOV replication ~10-fold in an infectious but biologically contained system. TRIM14-deficient mice are more susceptible to mouse-adapted EBOV infection. Co-immunoprecipitation, reporter assays (IFN-β and NF-κB promoters), viral replication assay, TRIM14 KO mice The Journal of infectious diseases Medium 37562033
2024 Co-immunoprecipitation confirmed a direct interaction between TRIM14 and KIF1B in kidney tubular epithelial cells under high-glucose conditions, with TRIM14 positively regulating KIF1B expression; TRIM14 knockdown suppresses the TLR4/NF-κB pathway and mitigates high-glucose-induced apoptosis, oxidative stress, and inflammation. Co-immunoprecipitation, transcriptome sequencing, knockdown, western blot (TLR4/NF-κB), in vitro HK-2 cell assays Diabetes, metabolic syndrome and obesity Low 41710718
2025 Co-immunoprecipitation assays revealed a potential interaction between TRIM14 and ATP7A (copper-exporting ATPase) in glioma cells, and combined TMZ and CuCl2 treatment suppresses TRIM14 expression and downregulates the TRIM14-ATP7A axis, inhibiting non-canonical NF-κB signaling and inducing cuproptosis. Co-immunoprecipitation, western blot, immunofluorescence, in vitro and in vivo xenograft models Biomedicines Low 41463095

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses. Molecular cell 324 27666593
2013 TRIM14 is a mitochondrial adaptor that facilitates retinoic acid-inducible gene-I-like receptor-mediated innate immune response. Proceedings of the National Academy of Sciences of the United States of America 118 24379373
2017 Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling. Molecular cell 68 29053956
2024 m6A-Mediated Upregulation of lncRNA CHASERR Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis. Molecular neurobiology 66 38193984
2018 TRIM14 promotes chemoresistance in gliomas by activating Wnt/β-catenin signaling via stabilizing Dvl2. Oncogene 65 29867201
2017 miR-195-5p Suppresses the Proliferation, Migration, and Invasion of Oral Squamous Cell Carcinoma by Targeting TRIM14. BioMed research international 65 29204446
2016 TRIM14 inhibits hepatitis C virus infection by SPRY domain-dependent targeted degradation of the viral NS5A protein. Scientific reports 61 27578425
2019 Inhibition of Influenza A Virus Replication by TRIM14 via Its Multifaceted Protein-Protein Interaction With NP. Frontiers in microbiology 60 30873142
2017 TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway. Scientific reports 58 28205534
2016 Overexpression of TRIM14 promotes tongue squamous cell carcinoma aggressiveness by activating the NF-κB signaling pathway. Oncotarget 55 26799420
2018 Identification of TRIM14 as a Type I IFN-Stimulated Gene Controlling Hepatitis B Virus Replication by Targeting HBx. Frontiers in immunology 52 30150992
2019 TRIM14 Promotes Noncanonical NF-κB Activation by Modulating p100/p52 Stability via Selective Autophagy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 50 31921549
2020 LncRNA KCNQ1OT1 contributes to the cisplatin resistance of tongue cancer through the KCNQ1OT1/miR-124-3p/TRIM14 axis. European review for medical and pharmacological sciences 49 31957833
2018 TRIM14 promotes colorectal cancer cell migration and invasion through the SPHK1/STAT3 pathway. Cancer cell international 47 30555277
2018 TRIM14 promotes the migration and invasion of gastric cancer by regulating epithelial‑to‑mesenchymal transition via activation of AKT signaling regulated by miR‑195‑5p. Oncology reports 46 30272351
2020 TRIM14 promotes endothelial activation via activating NF-κB signaling pathway. Journal of molecular cell biology 44 31070748
2020 TRIM14 Is a Key Regulator of the Type I IFN Response during Mycobacterium tuberculosis Infection. Journal of immunology (Baltimore, Md. : 1950) 44 32404352
2019 Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells. Journal of experimental & clinical cancer research : CR 44 30728039
2017 miR-15b inhibits cancer-initiating cell phenotypes and chemoresistance of cisplatin by targeting TRIM14 in oral tongue squamous cell cancer. Oncology reports 44 28350138
2018 TRIM14 Promotes Breast Cancer Cell Proliferation by Inhibiting Apoptosis. Oncology research 42 29562956
2020 Circ_0005198 enhances temozolomide resistance of glioma cells through miR-198/TRIM14 axis. Aging 41 33316781
2020 Trim14 promotes autophagy and chemotherapy resistance of gastric cancer cells by regulating AMPK/mTOR pathway. Drug development research 40 32096264
2017 TRIM14 is a Putative Tumor Suppressor and Regulator of Innate Immune Response in Non-Small Cell Lung Cancer. Scientific reports 37 28059079
2021 Human mesenchymal stem cells derived exosomes inhibit the growth of acute myeloid leukemia cells via regulating miR-23b-5p/TRIM14 pathway. Molecular medicine (Cambridge, Mass.) 35 34656078
2022 Exosomal circ_0091741 promotes gastric cancer cell autophagy and chemoresistance via the miR-330-3p/TRIM14/Dvl2/Wnt/β-catenin axis. Human cell 34 36323918
2019 TRIM14 promotes cell proliferation and inhibits apoptosis by suppressing PTEN in colorectal cancer. Cancer management and research 32 31296997
2017 The Ubiquitin Ligase RNF125 Targets Innate Immune Adaptor Protein TRIM14 for Ubiquitination and Degradation. Journal of immunology (Baltimore, Md. : 1950) 31 28476934
2019 TNF-α induces apoptosis of human nucleus pulposus cells via activating the TRIM14/NF-κB signalling pathway. Artificial cells, nanomedicine, and biotechnology 30 31322007
2015 Enhanced expression of trim14 gene suppressed Sindbis virus reproduction and modulated the transcription of a large number of genes of innate immunity. Immunologic research 30 25948474
2022 LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS. Journal of translational medicine 29 35962353
2022 TRIM14 inhibits OPTN-mediated autophagic degradation of KDM4D to epigenetically regulate inflammation. Proceedings of the National Academy of Sciences of the United States of America 28 35145029
2024 Targeting the TRIM14/USP14 Axis Enhances Immunotherapy Efficacy by Inducing Autophagic Degradation of PD-L1. Cancer research 27 38924473
2021 Circ_0004104 knockdown alleviates oxidized low-density lipoprotein-induced dysfunction in vascular endothelial cells through targeting miR-328-3p/TRIM14 axis in atherosclerosis. BMC cardiovascular disorders 27 33892646
2023 Targeting TCF19 sensitizes MSI endometrial cancer to anti-PD-1 therapy by alleviating CD8+ T cell exhaustion via TRIM14-IFN-β axis. Cell reports 25 37566545
2021 TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways. Aging 22 33982666
2021 Long non-coding RNA OIP5-AS1 contributes to cisplatin resistance of oral squamous cell carcinoma through the miR-27b-3p/TRIM14 axis. Experimental and therapeutic medicine 20 33692839
2022 Hypoxia-Induced Upregulation of lncRNA ELFN1-AS1 Promotes Colon Cancer Growth and Metastasis Through Targeting TRIM14 via Sponging miR-191-5p. Frontiers in pharmacology 17 35652045
2017 Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway. Experimental and therapeutic medicine 15 29467844
2023 TRIM14 Overexpression Induces Chemoresistance and Malignant Behaviors of Hepatocellular Carcinoma Cells by Activating the STAT3/HIF-1α Pathway. International journal of molecular sciences 14 37628777
2021 Inhibition of TRIM14 protects cerebral ischemia/reperfusion injury through regulating NF-κB/NLRP3 pathway-mediated inflammation and apoptosis. Journal of receptor and signal transduction research 14 33691569
2022 Circ_ROBO2/miR-186-5p/TRIM14 axis regulates oxidized low-density lipoprotein-induced cardiac microvascular endothelial cell injury. Regenerative therapy 13 35620639
2021 LncRNA MSC-AS1 Promotes Colorectal Cancer Progression by Regulating miR-325/TRIM14 Axis. Journal of oncology 13 34054957
2021 miR-671-5p repressed progression of papillary thyroid carcinoma via TRIM14. The Kaohsiung journal of medical sciences 13 34292652
2024 Emerging discoveries on the role of TRIM14: from diseases to immune regulation. Cell death discovery 12 39719450
2023 CircIRAK1 aggravates ox-LDL-induced endothelial cell injury in atherosclerosis via TRIM14 upregulation by binding to miR-330-5p. Clinical hemorheology and microcirculation 12 36336926
2021 miR-4443 targets TRIM14 to suppress metastasis and energy metabolism of papillary thyroid carcinoma (PTC) in vitro. Cell biology international 12 34051007
2025 Targeting the TRIM14/USP14 axis enhances radiotherapy efficacy by inducing GPX4 degradation and disrupting ferroptotic defense in HCC. Cell death & disease 11 40595451
2019 The TRIM14 PRYSPRY domain mediates protein interaction via its basic interface. FEBS letters 11 30973643
2023 An Antiviral Role for TRIM14 in Ebola Virus Infection. The Journal of infectious diseases 10 37562033
2024 Circ_RPPH1 facilitates progression of breast cancer via miR-1296-5p/TRIM14 axis. Cancer biology & therapy 9 38816350
2023 Circular RNA circ_0000741/miR-379-5p/TRIM14 signaling axis promotes HDAC inhibitor (SAHA) tolerance in glioblastoma. Metabolic brain disease 9 36905560
2023 RNF125, transcriptionally regulated by NFATC2, alleviates osteoarthritis via inhibiting the Wnt/β-catenin signaling pathway through degrading TRIM14. International immunopharmacology 9 37951197
2013 Trim14 overexpression causes the same transcriptional changes in mouse embryonic stem cells and human HEK293 cells. In vitro cellular & developmental biology. Animal 9 24092016
2025 Cannabidiol-loaded hydrogel microneedle patches inhibit TRIM14/TRAF3/ NF-κB axis for the treatment of psoriasis. International journal of biological macromolecules 8 39933682
2025 TRIM14 restricts tembusu virus infection through degrading viral NS1 protein and activating type I interferon signaling. PLoS pathogens 8 40435148
2021 Human TRIM14 protects transgenic mice from influenza A viral infection without activation of other innate immunity pathways. Genes and immunity 8 33864033
2019 TRIM14 expression is regulated by IRF-1 and IRF-2. FEBS open bio 8 31150153
2022 Piperlongumine-inhibited TRIM14 signaling sensitizes glioblastoma cells to temozolomide treatment. Life sciences 7 36202175
2018 Expression of the human TRIM14 and its mutant form (P207L) promotes apoptosis in transgenic loaches. Molecular biology reports 7 30203243
2024 Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients. Neuroscience 6 38697463
2022 The TRIM14-USP14-BRCC3 complex epigenetically regulates inflammation through inhibiting OPTN-mediated autophagic degradation of KDM4D. Autophagy 5 35311471
2021 Trim14 promotes osteoclastogenesis and noncanonical NF-κB activation by targeting p100/p52 in chronic periodontitis. Oral diseases 5 33901321
2024 TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway. Carcinogenesis 4 38267812
2025 Identification of TRIM21 and TRIM14 as Antiviral Factors Against Langat and Zika Viruses. Viruses 3 40431659
2017 Unexpected Alliance of WHIP-TRIM14-PPP6C to Combat Viruses. Molecular cell 2 29053952
2026 The TRIM14-KIF1B Axis Drives Renal Injury in Diabetic Nephropathy Through TLR4/NF-κB Pathway Modulation. Diabetes, metabolic syndrome and obesity : targets and therapy 1 41710718
2025 TRIM14-NF-κB pathway in the anterior cingulate cortex modulates comorbid depressive symptoms in chronic pain. Molecular pain 1 40200729
2025 TRIM14 Inhibition Suppresses Microglial Polarization and Pyroptosis Through the NF-κB/NLRP3 Pathway to Enhance Spinal Cord Injury Repair. Mediators of inflammation 1 41250673
2025 TRIM14 Regulation of Copper Homeostasis and Cuproptosis: A New Strategy to Overcome Chemoresistance in Glioblastoma. Biomedicines 0 41463095
2022 Corrigendum to "miR-195-5p Suppresses the Proliferation, Migration, and Invasion of Oral Squamous Cell Carcinoma by Targeting TRIM14". BioMed research international 0 35601146

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