Affinage

TRIM56

E3 ubiquitin-protein ligase TRIM56 · UniProt Q9BRZ2

Length
755 aa
Mass
81.5 kDa
Annotated
2026-06-10
49 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM56 is a RING-type E3 ubiquitin ligase that operates as a central node in innate antiviral immunity and, through substrate-specific ubiquitination, in a wide range of cellular processes (PMID:21074459, PMID:29426904, PMID:35062293). In DNA-sensing immunity it monoubiquitinates cGAS at Lys335 to enhance cGAS dimerization, DNA binding, and cGAMP production, with TRIM56-deficient mice showing impaired type I interferon and heightened HSV-1 susceptibility (PMID:29426904); this cGAS-activating function is restrained by HDAC6-mediated deacetylation of TRIM56 at K110, a circuit exploited by the HSV-1 US3 protein (PMID:39747662). TRIM56 also catalyzes K63-linked ubiquitination of STING to induce dimerization and TBK1 recruitment for IFN-β induction against cytosolic dsDNA (PMID:21074459), and potentiates TLR3-TRIF signaling through a phosphorylation-dependent interaction with TRIF that requires Ser471/Ser475/Ser710 and the coiled-coil domain rather than ligase activity (PMID:22948160, PMID:38556084); genetic ablation places TRIM56 upstream of IFN production in both the dsRNA/TLR3 and cGAS-STING arms (PMID:35062293). Independently of its ligase activity, TRIM56 acts as an RNA-binding protein whose short C-terminal tail directly binds viral RNA and restricts flaviviruses, influenza, and other RNA viruses (PMID:25253338, PMID:26889027, PMID:31251739). Beyond immunity, TRIM56 governs diverse physiology by degrading or modifying defined substrates: it drives K48-linked degradation of FASN to limit hepatic lipogenesis (PMID:38206764), of TLE3 to promote beige adipogenesis (PMID:39928840), of vimentin to suppress EMT (PMID:28771721), and of KLF4, YBX1, and GCN2 in neuronal and tumor contexts (PMID:39291396, PMID:41214892, PMID:41413248), while catalyzing non-degradative K63-linked modification of IQGAP1 and Src to activate downstream CDC42 and Src signaling (PMID:36870986, PMID:41102183). The coiled-coil domain assembles an anti-parallel tetramer that juxtaposes RING domains for efficient ubiquitin transfer (PMID:37168870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2010 High

    Established the first mechanistic role for TRIM56 in innate immunity by showing it ubiquitinates STING to enable antiviral signaling, answering how cytosolic DNA sensing engages an E3 ligase.

    Evidence Co-IP, K63-ubiquitination assays, and IFN-β reporter with knockdown in dsDNA response

    PMID:21074459

    Open questions at the time
    • Did not resolve which E2 partners with TRIM56 on STING
    • Physiological requirement not yet tested in knockout animals
  2. 2011 Medium

    Showed TRIM56 directly restricts a virus (BVDV) in a ligase- and C-terminus-dependent manner separable from general IFN induction, indicating intrinsic antiviral activity beyond signaling amplification.

    Evidence Overexpression/RNAi viral replication assays with ligase-dead and deletion mutants

    PMID:21289118

    Open questions at the time
    • Direct viral or host substrate not identified
    • Mechanism by which the C-terminus contributes was unresolved
  3. 2012 High

    Defined a ligase-independent function in which TRIM56 binds the adaptor TRIF to potentiate TLR3 signaling, distinguishing scaffolding from catalytic roles.

    Evidence Reciprocal Co-IP, C-terminal deletion mutants, IRF3/IFN-β reporter assays

    PMID:22948160

    Open questions at the time
    • How TRIM56 binding alters TRIF complex assembly was not defined
    • Did not address whether the interaction is constitutive or stimulus-induced
  4. 2014 High

    Demonstrated virus-specific restriction mechanisms, requiring ligase activity plus C-terminal integrity for flaviviruses but ligase alone for a coronavirus, showing TRIM56 uses distinct modes against different viruses.

    Evidence Tet-regulated conditional mutant cell lines, viral RNA quantification, RING and deletion mutants

    PMID:25253338

    Open questions at the time
    • The molecular target restricting flavivirus RNA accumulation was unknown at this stage
    • Step in coronavirus life cycle beyond 'post-replication' undefined
  5. 2016 High

    Localized RNA-virus restriction to a minimal 63-residue C-terminal tail sufficient on its own, separating antiviral function from the RING, B-box, and coiled-coil domains.

    Evidence Domain deletion and minimal-fragment expression with influenza RNA synthesis assays

    PMID:26889027

    Open questions at the time
    • Biochemical activity of the tail not yet defined as RNA binding
    • Did not establish whether the tail acts directly on viral or host machinery
  6. 2018 High

    Identified cGAS as a direct activating substrate via monoubiquitination at K335 and confirmed in vivo requirement, providing a defined biochemical mechanism for TRIM56's pro-IFN role against DNA viruses.

    Evidence Site-specific ubiquitination mapping, cGAS dimerization/cGAMP assays, TRIM56-KO mice, HSV-1 model

    PMID:29426904

    Open questions at the time
    • Relationship between cGAS monoubiquitination and the earlier STING K63 model not reconciled
    • E2 enzyme for cGAS modification not identified
  7. 2019 High

    Demonstrated that TRIM56 is a bona fide RNA-binding protein whose C-terminal region directly binds viral RNA, explaining the ligase-independent restriction defined earlier.

    Evidence Cell-free RNA binding with recombinant fragment, RIP, Dicer-KO controls, ZIKV replication assays

    PMID:31251739

    Open questions at the time
    • RNA sequence/structure specificity of binding not defined
    • How RNA binding mechanistically blocks replication unresolved
  8. 2017 Medium

    Extended TRIM56 function beyond immunity by identifying vimentin as a degradative substrate, linking the ligase to EMT suppression in epithelial cells.

    Evidence MS of vimentin IP, proteasome inhibitor rescue, OE/KD migration/invasion assays

    PMID:28771721

    Open questions at the time
    • Ubiquitination site and linkage on vimentin not mapped
    • Single-lab finding without in vivo validation
  9. 2022 High

    Clarified pathway placement by showing TRIM56 is required upstream of IFN production (dsRNA/TLR3 and cGAS-STING) but not in downstream IFN signaling, defining the boundary of its requirement.

    Evidence CRISPR TRIM56-null HeLa cells, ISG assays across pathways with negative controls, VSV bioassay

    PMID:35062293

    Open questions at the time
    • Did not dissect relative contributions of cGAS vs STING modification
    • Cell-type generality beyond HeLa not addressed
  10. 2023 Medium

    Provided a structural basis for catalysis by showing the coiled-coil forms an anti-parallel tetramer positioning RING domains for ubiquitin transfer.

    Evidence X-ray crystallography of isolated coiled-coil domain and tetramer modeling

    PMID:37168870

    Open questions at the time
    • No mutagenesis validation of the proposed tetramer interface
    • Structure of full-length protein and RING-substrate engagement not determined
  11. 2024 High

    Defined the regulatory layer controlling TRIM56's cGAS function, showing HDAC6 deacetylates TRIM56 at K110 to suppress cGAS monoubiquitination, a node hijacked by HSV-1 US3.

    Evidence HDAC6 KO in vitro/in vivo, K110 acetylation mapping, cGAS monoubiquitination and DNA-binding assays, HSV-1 model

    PMID:39747662

    Open questions at the time
    • The acetyltransferase opposing HDAC6 on TRIM56 not identified
    • Whether K110 acetylation affects non-cGAS substrates unknown
  12. 2024 High

    Established TRIM56's metabolic role by identifying FASN as a K48-linked degradative substrate that restrains hepatic lipogenesis, expanding its physiology to NAFLD.

    Evidence Co-IP, K48 ubiquitination, hepatocyte-specific KO/OE mice, interactome/transcriptome profiling

    PMID:38206764

    Open questions at the time
    • Ubiquitination site on FASN not mapped
    • Upstream signals controlling hepatic TRIM56 expression not defined
  13. 2024 High

    Refined TLR3 regulation by showing site-specific TRIM56 phosphorylation (Ser471/Ser475/Ser710) governs the TRIF interaction, providing a phospho-switch for signal augmentation.

    Evidence Phospho-specific antibodies, alanine mutants, Tet-regulated cells, TRIM56-TRIF Co-IP, IFN-β reporter

    PMID:38556084

    Open questions at the time
    • The kinase phosphorylating these residues not identified
    • How phosphorylation alters TRIM56 conformation/binding not structurally resolved
  14. 2022 Medium

    Broadened TRIM56's catalytic repertoire to non-canonical signaling and apparent deubiquitination, modifying TAK1 (M1-linked), IQGAP1 (K48-to-K63 switch), Src (K63), and stabilizing cIAP1 and FOXM1.

    Evidence Co-IP, linkage-specific ubiquitination, downstream activation assays across glioma/cancer models (multiple studies)

    PMID:35696011 PMID:35952808 PMID:36471347 PMID:36870986 PMID:41102183

    Open questions at the time
    • Mechanism by which a RING E3 effects deubiquitination/stabilization not biochemically resolved
    • Each substrate validated in a single lab without cross-replication
  15. 2024 Medium

    Showed TRIM56 substrate engagement is directed by adaptors and lncRNAs, with ZC3H15 recruiting it to PTEN and PVT1 modulating AMPKα ubiquitination, indicating context-specific targeting.

    Evidence Co-IP, domain mapping, ubiquitination assays, conditional KO mice (PVT1/TRIM56 podocyte models)

    PMID:39349450 PMID:41513632

    Open questions at the time
    • General rules determining substrate selection across tissues unknown
    • Whether adaptor recruitment competes with antiviral substrates not addressed
  16. 2025 Medium

    Documented a contradictory STING outcome, with TRIM56 driving K48-linked STING degradation to dampen inflammation, contrasting its earlier K63-linked STING activation.

    Evidence Co-IP, K48 ubiquitination, MG132 rescue, OE/KD in LPS-induced acute lung injury model

    PMID:42155789

    Open questions at the time
    • Conditions selecting K48 versus K63 modification of STING not defined
    • Direct contradiction with the 2010 STING-activation model unreconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIM56 selects among its many substrates and switches between activating (K63/mono), degradative (K48), and stabilizing outputs in a context-dependent manner remains unresolved.
  • No unifying model for linkage-type and substrate selection
  • Conflicting STING modifications (K63 activation vs K48 degradation) not mechanistically reconciled
  • No full-length structure showing RING-substrate engagement

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 6 GO:0140096 catalytic activity, acting on a protein 4 GO:0016874 ligase activity 3 GO:0003723 RNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1430728 Metabolism 2
Partners
CGASFASNIQGAP1SRCSTING1TICAM1TLE3YBX1
Complex memberships
ATR-TRIM56 complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 TRIM56 is an E3 ubiquitin ligase that interacts with STING and targets it for K63-linked ubiquitination, which induces STING dimerization; this dimerization is a prerequisite for recruitment of the antiviral kinase TBK1 and subsequent IFN-β induction in response to cytosolic dsDNA. Co-immunoprecipitation, overexpression and knockdown with IFN-β promoter reporter assay, ubiquitination assays Immunity High 21074459
2011 TRIM56 restricts bovine viral diarrhea virus (BVDV) replication in a manner dependent on its E3 ubiquitin ligase activity and the integrity of its C-terminal region, but independent of any general augmentation of the interferon response or effects on IRF3 stability. Overexpression and RNAi knockdown with viral replication assays; E3 ligase-dead mutant analysis; domain deletion mapping Journal of virology Medium 21289118
2012 TRIM56 positively regulates TLR3 signaling by physically interacting with the adaptor protein TRIF; this interaction (mediated by the C-terminal portion of TRIM56, residues 621–750) is required for potentiation of IRF3 activation and IFN-β induction, independent of E3 ligase activity. Co-immunoprecipitation, overexpression and knockdown with IRF3 activation and IFN-β reporter assays, C-terminal deletion mutants The Journal of biological chemistry High 22948160
2014 TRIM56 restricts yellow fever virus (YFV) and dengue virus serotype 2 (DENV2) by suppressing intracellular viral RNA accumulation, requiring both E3 ligase activity (RING domain) and C-terminal integrity; restriction of HCoV-OC43 requires only E3 ligase activity and acts at a post-RNA-replication step in the viral life cycle. Conditional mutant cell lines (Tet-regulated), viral RNA quantification, domain deletion and RING mutant analysis Journal of virology High 25253338
2016 TRIM56 restricts influenza A and B viruses by impeding intracellular viral RNA synthesis via its short 63-residue C-terminal tail segment, independently of E3 ligase activity, B-box, or coiled-coil domain; expression of this tail segment alone was sufficient for antiviral activity. Domain deletion mutants, E3 ligase-dead mutant, overexpression/knockdown with viral RNA synthesis assays Journal of virology High 26889027
2017 TRIM56 functions as an E3 ubiquitin ligase that ubiquitinates and targets vimentin for proteasomal degradation in normal ovarian epithelial cells, thereby suppressing EMT and cell migration/invasion; loss of TRIM56 in ovarian cancer cells leads to vimentin stabilization. Mass spectrometry of vimentin immunoprecipitate, RNAi knockdown and overexpression, proteasome inhibitor assay, in vitro migration/invasion Journal of cellular physiology Medium 28771721
2018 TRIM56 E3 ligase induces monoubiquitination of cGAS at Lys335, which markedly increases cGAS dimerization, DNA-binding activity, and cGAMP production, thereby promoting IFN-αβ production against DNA viruses; TRIM56-deficient mice show impaired IFN-αβ and high susceptibility to HSV-1. Ubiquitination assays (monoubiquitination site mapping), cGAS dimerization assays, cGAMP ELISA, TRIM56-KO mice, HSV-1 infection model Nature communications High 29426904
2018 TRIM56 interacts with the AF1 domain of estrogen receptor alpha (ERα) via its WD40 domain in the cytoplasm and promotes K63-linked ubiquitination of ERα, prolonging ERα protein stability and sustaining estrogen signaling in breast cancer cells. Co-immunoprecipitation, domain mapping (WD40 deletion), ubiquitination assay, TRIM56 knockdown with ERα stability measurement Oncogenesis Medium 31000690
2019 TRIM56 is an RNA-binding protein; its C-terminal 392 residues directly bind ZIKV RNA in cell-free reactions, and deletion of a short C-terminal tail abrogates both ZIKV RNA binding and antiviral activity; miRNA pathway (Dicer) was not required for TRIM56-mediated ZIKV restriction. RNA immunoprecipitation, cell-free RNA binding assay with recombinant TRIM56 fragment, Dicer-KO cells, ZIKV RNA replication assays, C-terminal deletion mutants PLoS neglected tropical diseases High 31251739
2019 KSHV vFLIP recruits TRIM56 E3 ubiquitin ligase to degrade SAP18 via the ubiquitin-proteasome pathway, disrupting the SAP18-HDAC1 complex, leading to enhanced p65 acetylation and NF-κB activation that promotes cell invasion and angiogenesis. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor rescue, overexpression/knockdown functional assays Cell death and differentiation Medium 30670829
2022 TRIM56 promotes TNFα-induced NF-κB signaling by interacting with TAK1 and enhancing its M1-linked polyubiquitination, which strengthens TAK1-IKKα complex formation; the C-terminal domain of TRIM56 mediates TAK1 binding and the RING domain provides E3 activity. Co-immunoprecipitation, ubiquitination assay (M1-linkage specific), overexpression/knockdown with NF-κB reporter assays, domain mapping International journal of biological macromolecules Medium 35952808
2022 TRIM56 deubiquitinates and stabilizes cIAP1 mainly through its zinc-finger domain (residues 21–205), protecting cIAP1 from degradation and thereby promoting glioma cell survival and progression. Co-immunoprecipitation, Human Ubiquitin Array, domain deletion mutants, overexpression/knockdown with cIAP1 stability assays Journal of experimental & clinical cancer research Medium 36471347
2022 TRIM56 stabilizes FOXM1 protein through deubiquitination, enhancing DNA damage repair in glioblastoma cells and reducing radiosensitivity; interaction between TRIM56 and FOXM1 was confirmed by Co-IP. Co-immunoprecipitation, ubiquitination assay, TRIM56 knockdown/overexpression with DNA repair and radiosensitivity assays, xenograft model Molecular neurobiology Medium 35696011
2022 TRIM56 inhibits HBV replication by translocating from cytoplasm to nucleus (requiring C-terminal domain) during HBV infection, where its RING domain targets IκBα for ubiquitination, leading to p65 phosphorylation and NF-κB-mediated suppression of HBV core promoter activity. Subcellular fractionation/localization, domain deletion mutants, ubiquitination assay, NF-κB reporter, HBV replication assay in HepG2-NTCP and primary human hepatocytes Antiviral research Medium 36084850
2022 TRIM56 knockout in HeLa cells severely impairs ISG upregulation in response to extracellular dsRNA (TLR3 pathway) and weakens cytosolic dsDNA (cGAS-STING pathway) responses, but does not compromise IFN-α-induced ISG induction or ISGylation, establishing TRIM56 as specifically required upstream of IFN production rather than in downstream IFN signaling. CRISPR/Cas9 gene editing (TRIM56 null cell lines), ISG expression assays, VSV antiviral bioactivity assay Viruses High 35062293
2023 The crystal structure of the TRIM56 coiled-coil domain reveals two anti-parallel dimers forming a tetramer, which positions two RING domains on each side to form an active homodimer that facilitates ubiquitin transfer from E2 to substrate. X-ray crystallography of coiled-coil domain, structural analysis of tetramer architecture Computational and structural biotechnology journal Medium 37168870
2023 TRIM56 promotes glioma cell migration and invasion by interacting with IQGAP1 and promoting a K48-to-K63-linked polyubiquitination transition of IQGAP1 at Lys1230, which activates CDC42 downstream; TRIM56 is transcriptionally regulated by SP1. Co-immunoprecipitation, ubiquitination assay (K48/K63 linkage-specific), CDC42 activation assay, in vitro/in vivo migration/invasion assays, SP1 knockdown Cell death & disease Medium 36870986
2024 TRIM56 directly interacts with and induces K48-linked ubiquitination-dependent proteasomal degradation of fatty acid synthase (FASN) in hepatocytes, limiting lipogenesis; loss of hepatic TRIM56 exacerbates NAFLD while overexpression suppresses it. Co-immunoprecipitation, ubiquitination assay (K48-linkage), hepatocyte-specific KO and OE mouse models, interactome and transcriptome profiling, AI-based virtual screening of FASN inhibitor The Journal of clinical investigation High 38206764
2024 TRIM56 phosphorylation at Ser471 and Ser475 (occurring biphasically early after TLR3 stimulation, prior to IRF3 phosphorylation) and at Ser710 is required for augmentation of TLR3 signaling; the Coiled-coil domain and residues ~434-610 are also required; Ser710Ala mutation specifically disrupts the TRIM56-TRIF interaction. Phospho-specific antibody detection, alanine-substitution mutants, Tet-regulated cell lines, TRIM56-TRIF Co-IP, IFN-β reporter assay, antiviral state assay The Journal of biological chemistry High 38556084
2024 TRIM56 is part of an ATR-TRIM56 complex in nucleus pulposus cells; disassembly of this complex during senescence frees USP5 and TRIM25, causing ATR ubiquitination to switch from K63- to K48-linked modification, thereby promoting proteasomal degradation of ATR, leading to cytosolic DNA accumulation and cGAS/STING-dependent inflammatory senescence. Co-immunoprecipitation, ubiquitination assay (K63/K48 linkage), ATR conditional KO, cGAS/STING pathway activation assays, extracellular vesicle delivery of ATR plasmid The Journal of clinical investigation Medium 38488012
2024 TRIM56 restricts Coxsackievirus B3 (CVB3) by interacting with the viral RNA-dependent RNA polymerase 3D protein and mediating its K48-linked polyubiquitination at K220, promoting proteasomal degradation; the viral 3C protease cleaves TRIM56 to counter this restriction. Pulldown and Co-immunoprecipitation, immunofluorescence colocalization, proteasome inhibitor assay, ubiquitination assay (K48 site mapping), viral yield assay PLoS pathogens Medium 39348396
2024 HDAC6 deacetylates TRIM56 at K110 (in mice), impairing TRIM56-mediated monoubiquitination of cGAS and reducing cGAS DNA-binding ability, thereby suppressing type I IFN production; the HSV-1 viral protein US3 phosphorylates HDAC6 to exploit this mechanism. HDAC6 knockout (in vitro and in vivo), acetylation site mapping (K110), monoubiquitination assay of cGAS, DNA-binding assay, HSV-1 infection model, US3-HDAC6 phosphorylation assay EMBO reports High 39747662
2024 TRIM56 binds to YBX1 and promotes its K48-linked ubiquitination and proteasomal degradation, reducing YBX1-mediated stabilization of Zbp1 mRNA and thereby limiting ZBP1-mediated PANoptosis in neurons after spinal cord injury. Molecular docking, IP/MS, Co-immunoprecipitation, ubiquitination assay, RIP-seq, TRIM56 knockdown/overexpression with PANoptosis readouts Advanced science Medium 39291396
2024 LncRNA PVT1 interacts with TRIM56 post-transcriptionally to modulate the ubiquitination of AMPKα, leading to aberrant mitochondrial biogenesis and fission in podocytes; podocyte-specific Trim56 KO mice phenocopied PVT1 KO mice, confirming TRIM56 mediates PVT1's mitochondrial effects. Co-immunoprecipitation, ubiquitination assay, conditional KO mice (Nphs2-Cre/Trim56flox/flox and Nphs2-Cre/Pvt1flox/flox), mitochondrial function assays Cell death & disease Medium 39349450
2025 TRIM56 promotes K48-linked ubiquitination and proteasomal degradation of TLE3 in adipocytes in response to cold stimuli, activating thermogenic gene programs in subcutaneous white adipose tissue to promote beige adipogenesis and protect against diet-induced obesity. Co-immunoprecipitation, ubiquitination assay (K48-linkage), adipocyte-specific TRIM56 OE mice, cold challenge, metabolic phenotyping Advanced science Medium 39928840
2025 TRIM56 directly interacts with the SH3 domain of Src via its B-box1 domain and catalyzes K63-linked polyubiquitination of Src at Lys184, promoting Src aggregation and intermolecular autophosphorylation-driven activation, thereby promoting HCC progression. Co-immunoprecipitation, domain mapping (B-box1), ubiquitination assay (K63-linkage, site K184), Src activation assays Cell death & disease Medium 41102183
2025 TRIM56 directly interacts with KLF4 and promotes its K48-linked ubiquitination-dependent proteasomal degradation, leading to neuronal ferroptosis; TRIM56 knockout mice show reduced neurological deficits and inflammation after cerebral ischemia-reperfusion injury. Co-immunoprecipitation, ubiquitination assay (K48-linkage), TRIM56 KO mice with I/R model, ferroptosis markers, compound screening for TRIM56 inhibitor (farudodstat) Advanced science Medium 41214892
2025 TRIM56 stabilizes the adenoviral E1A protein and enhances viral genome transcription during HAdV-C5 infection; TRIM56 also assists E1A in antagonizing STING, thereby promoting adenoviral replication. Overexpression/knockdown with E1A stability assays, viral replication assays, recombinant OAV-TRIM56 construction and in vitro/in vivo efficacy testing Journal of virology Medium 40459263
2026 TRIM56 promotes K48-linked ubiquitination and proteasomal degradation of GCN2 at K619, thereby inhibiting the GCN2/EIF2α/ATG12 axis; CD147 suppresses TRIM56 expression to stabilize GCN2 and drive secretory autophagy-mediated exosome release and NSCLC metastasis. Proteomics (E3 ligase identification), Co-immunoprecipitation, ubiquitination assay (K48, site K619), TRIM56 knockdown/overexpression, in vitro and in vivo metastasis models Cell death and differentiation Medium 41413248
2026 ZC3H15 recruits TRIM56 to ubiquitinate PTEN, promoting its degradation and activating AKT-mTOR signaling in NSCLC; ZC3H15 binds PTEN through its DFRP domain. Co-immunoprecipitation, ubiquitination assay, domain mapping (DFRP), overexpression/knockdown with AKT-mTOR pathway assays Cell death & disease Medium 41513632
2026 TRIM56 directly binds to STING in the cytoplasm and promotes its K48-linked ubiquitination and proteasomal degradation, thereby inhibiting M1 macrophage polarization and reducing sepsis-induced acute lung injury; this is distinct from TRIM56's previously described K63-linked activation of STING. Immunofluorescence co-localization, Co-immunoprecipitation, ubiquitination assay (K48-linkage), MG132 proteasome inhibitor rescue, TRIM56 OE/KD in vitro and in vivo (LPS-induced ALI model) Cellular signalling Medium 42155789
2024 TRIM56 was identified by mass spectrometry as the E3 ligase targeting AHR for ubiquitination in NSCLC; PGRMC1 overexpression inhibits the TRIM56-AHR interaction, stabilizing AHR and maintaining cancer stem cell phenotypes. Mass spectrometry screening, Co-immunoprecipitation, TRIM56-AHR interaction assay, overexpression/knockdown functional assays Biochimica et biophysica acta. Molecular basis of disease Medium 39059592

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity 431 21074459
2018 TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing. Nature communications 195 29426904
2011 TRIM56 is a virus- and interferon-inducible E3 ubiquitin ligase that restricts pestivirus infection. Journal of virology 101 21289118
2016 The C-Terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis. Journal of virology 93 26889027
2012 TRIM56 is an essential component of the TLR3 antiviral signaling pathway. The Journal of biological chemistry 93 22948160
2014 Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus. Journal of virology 90 25253338
2022 Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1. Journal of experimental & clinical cancer research : CR 71 36209117
2019 Regulation of estrogen signaling and breast cancer proliferation by an ubiquitin ligase TRIM56. Oncogenesis 67 31000690
2024 TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase. The Journal of clinical investigation 59 38206764
2017 The ubiquitin ligase TRIM56 inhibits ovarian cancer progression by targeting vimentin. Journal of cellular physiology 53 28771721
2019 The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. PLoS neglected tropical diseases 46 31251739
2024 Disassembly of the TRIM56-ATR complex promotes cytoDNA/cGAS/STING axis-dependent intervertebral disc inflammatory degeneration. The Journal of clinical investigation 43 38488012
2019 Suppression of the SAP18/HDAC1 complex by targeting TRIM56 and Nanog is essential for oncogenic viral FLICE-inhibitory protein-induced acetylation of p65/RelA, NF-κB activation, and promotion of cell invasion and angiogenesis. Cell death and differentiation 40 30670829
2024 TRIM56 Modulates YBX1 Degradation to Ameliorate ZBP1-Mediated Neuronal PANoptosis in Spinal Cord Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 34 39291396
2024 Key roles for phosphorylation and the Coiled-coil domain in TRIM56-mediated positive regulation of TLR3-TRIF-dependent innate immunity. The Journal of biological chemistry 31 38556084
2022 TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein. Journal of experimental & clinical cancer research : CR 29 36471347
2023 The Functions of TRIM56 in Antiviral Innate Immunity and Tumorigenesis. International journal of molecular sciences 28 36902478
2022 TRIM56 positively regulates TNFα-induced NF-κB signaling by enhancing the ubiquitination of TAK1. International journal of biological macromolecules 26 35952808
2018 TRIM56 Suppresses Multiple Myeloma Progression by Activating TLR3/TRIF Signaling. Yonsei medical journal 24 29214775
2022 TRIM56 impairs HBV infection and replication by inhibiting HBV core promoter activity. Antiviral research 22 36084850
2023 TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion. Cell death & disease 19 36870986
2022 TRIM56 Reduces Radiosensitization of Human Glioblastoma by Regulating FOXM1-Mediated DNA Repair. Molecular neurobiology 17 35696011
2018 Poly r(C) Binding Protein 1 Regulates Posttranscriptional Expression of the Ubiquitin Ligase TRIM56 in Ovarian Cancer. IUBMB life 16 30281912
2024 LncRNA PVT1 induces mitochondrial dysfunction of podocytes via TRIM56 in diabetic kidney disease. Cell death & disease 13 39349450
2021 TRIM56 suppresses the malignant development of hepatocellular carcinoma via targeting RBM24 and inactivating the Wnt signaling. European review for medical and pharmacological sciences 13 33577026
2021 Identification of TRIM56 as a Potential Biomarker for Lung Adenocarcinoma. Cancer management and research 13 33707970
2019 MiR-9 promotes multiple myeloma progression by regulating TRIM56/NF-κB pathway. Cell biology international 13 30637864
2024 TRIM56 restricts Coxsackievirus B infection by mediating the ubiquitination of viral RNA-dependent RNA polymerase 3D. PLoS pathogens 10 39348396
2022 TRIM56 overexpression restricts porcine epidemic diarrhoea virus replication in Marc-145 cells by enhancing TLR3-TRAF3-mediated IFN-β antiviral response. The Journal of general virology 10 35503719
2025 TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39928840
2022 New Avenues to Explore in SARS-CoV-2 Infection: Both TRIM25 and TRIM56 Positively Correlate with VEGF, GAS6, and sAXL in COVID-19 Patients. Viral immunology 8 36450108
2025 HDAC6 deacetylates TRIM56 to negatively regulate cGAS-STING-mediated type I interferon responses. EMBO reports 7 39747662
2023 TRIM56 coiled-coil domain structure provides insights into its E3 ligase functions. Computational and structural biotechnology journal 7 37168870
2020 Systematic review of the antiviral properties of TRIM56: a potential therapeutic intervention for COVID-19. Expert review of clinical immunology 7 32903131
2022 Impaired Antiviral Responses to Extracellular Double-Stranded RNA and Cytosolic DNA, but Not to Interferon-α Stimulation, in TRIM56-Deficient Cells. Viruses 6 35062293
2025 Emerging Roles of TRIM56 in Antiviral Innate Immunity. Viruses 3 39861861
2024 PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR. Biochimica et biophysica acta. Molecular basis of disease 3 39059592
2024 TRIM56-mediated production of type I interferon inhibits intracellular replication of Rickettsia rickettsii. Microbiology spectrum 2 38358243
2025 TRIM56 enhances adenoviral E1A steady state to improve oncolytic adenovirus therapy efficacy. Journal of virology 1 40459263
2025 TRIM56 Aggravates Cerebral Ischemia-Reperfusion Injury via Inhibiting KLF4-Activated Ferroptosis Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41214892
2026 ZC3H15 regulates the ubiquitination of PTEN via recruitment of TRIM56 and promotes malignant progression of non-small cell lung cancer. Cell death & disease 0 41513632
2026 Bufei formula attenuates airway mucus hypersecretion in COPD through inhibition of TRIM56-mediated ITGB4 ubiquitination. Journal of ethnopharmacology 0 41580166
2026 Kaempferol Ameliorates Non-Alcoholic Fatty Liver Disease by Targeting TRIM56 to Regulate Lipid Metabolism. International journal of molecular sciences 0 42123354
2026 TRIM56 inhibits M1 macrophage polarization and mitigates sepsis-induced acute lung injury via promoting STING ubiquitination-degradation. Cellular signalling 0 42155789
2025 The oncogenic role of TRIM56 in pancreatic cancer via the TRAF6/NF-kB axis. Journal of molecular histology 0 40542888
2025 The E3 ubiquitin ligase TRIM56 promotes aggregation and activation of Src protein through Lys63-linked polyubiquitination in hepatocellular carcinoma. Cell death & disease 0 41102183
2025 CD147 promotes NSCLC metastasis by inducing secretory autophagy-dependent exosome secretion via TRIM56-mediated ubiquitination and degradation of GCN2. Cell death and differentiation 0 41413248
2024 The regulation of innate antiviral immunity by TRIM56. Infectious diseases & immunity 0 42253598
2023 Expression of TRIM56 gene in SARS-CoV-2 variants and its relationship with progression of COVID-19. Future virology 0 38051999

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