Affinage

TRIM26

Tripartite motif-containing protein 26 · UniProt Q12899

Length
539 aa
Mass
62.2 kDa
Annotated
2026-06-10
52 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM26 is a RING-type E3 ubiquitin ligase that acts as a context-dependent regulator of innate immune signaling, DNA base-excision repair, and the stability of diverse oncogenic and metabolic proteins, with substrate recognition through its C-terminal PRY/SPRY domain and catalysis through its RING domain (PMID:25763818, PMID:37872147, PMID:37324936). In antiviral signaling, virus infection drives TRIM26 nuclear translocation, where it catalyzes K48-linked polyubiquitination and proteasomal degradation of phosphorylated, activated IRF3 to terminate the response (PMID:25763818); in parallel it autoubiquitinates and bridges TBK1 to NEMO at the VISA signalsome to activate TBK1 (PMID:26611359), and routes MAVS to NDP52-mediated selective autophagy (PMID:38965634). TRIM26 tunes NF-κB and MAPK output through linkage-specific ubiquitination of upstream adaptors, catalyzing K11-linked ubiquitination of TAB1 to promote TAK1 activation (PMID:34017102, PMID:42088415) and modulating TRAF2 and TRAF6 ubiquitination, with knockout mice showing altered inflammatory cytokine production and infection outcomes (PMID:40490503, PMID:41652078, PMID:34017102). In DNA repair, TRIM26 sets steady-state levels of the BER glycosylases NEIL1 and NTH1 by polyubiquitination at defined lysines, and its depletion stabilizes these enzymes and alters cellular resistance to ionizing radiation and oxidative stress (PMID:27924031, PMID:29610152, PMID:36232914). Across cancer biology TRIM26 targets a broad substrate set, most often for K48-linked degradation (ZEB1, TAF7, RACK1, PBX1, HSP-90β, NKRF, β-catenin, LDHA), but in the case of GPX4 it switches ubiquitination from K48 to K63 linkage to stabilize the protein and confer ferroptosis resistance, an interaction enhanced by PLK1-mediated phosphorylation of TRIM26 at S127 (PMID:33649471, PMID:37591850, PMID:37324936, PMID:38038978, PMID:42026030, PMID:37872147, PMID:41989643). TRIM26 is itself transcriptionally and post-transcriptionally controlled, being induced by TGF-β and E2F3 and regulated at the splicing and mRNA-stability level by USP39 and HuR (PMID:29203640, PMID:42088415, PMID:36707504, PMID:41746668).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2015 High

    Established TRIM26 as a negative-feedback brake on antiviral signaling by defining its first substrate and a spatial mechanism: virus-induced nuclear translocation to degrade activated IRF3.

    Evidence Co-IP, K48 ubiquitination assays, IRF3 phosphomimetic/NLS mutants, and transgenic mice

    PMID:25763818

    Open questions at the time
    • Did not resolve the signal triggering TRIM26 nuclear translocation
    • Did not address whether TRIM26 also acts at upstream signaling nodes
  2. 2015 Medium

    Showed TRIM26 also acts positively in the same pathway by autoubiquitinating and scaffolding the TBK1-NEMO interaction, revealing a dual pro- and anti-viral role.

    Evidence Co-IP, knockdown, autoubiquitination and reporter assays

    PMID:26611359

    Open questions at the time
    • The autoubiquitination linkage type and its E2 partner were not defined
    • How the positive (TBK1 bridging) and negative (IRF3 degradation) roles are temporally coordinated is unresolved
  3. 2016 High

    Extended TRIM26 function beyond immunity by identifying NEIL1 as an in vitro ubiquitylation substrate, linking TRIM26 to base-excision repair and radiation resistance.

    Evidence In vitro ubiquitylation with purified proteins, siRNA, protein stability and survival assays

    PMID:27924031

    Open questions at the time
    • Ubiquitin linkage type on NEIL1 not specified
    • In vivo relevance to genome stability not tested
  4. 2018 High

    Generalized the BER-regulation role by mapping NTH1 ubiquitylation to K67 and showing TRIM26 limits glycosylase accumulation on chromatin during oxidative stress.

    Evidence In vitro ubiquitylation, K67R mutant, siRNA, chromatin fractionation

    PMID:29610152

    Open questions at the time
    • Whether the same regulation operates under physiological damage loads in vivo unclear
  5. 2018 Medium

    Placed TRIM26 in a growth-control circuit, showing TGF-β induces TRIM26 to degrade the TFIID subunit TAF7 and arrest proliferation, with MYC antagonizing this induction.

    Evidence Transcriptional induction, Co-IP, ubiquitination and proliferation assays in mammary epithelial cells

    PMID:29203640

    Open questions at the time
    • TAF7 ubiquitination linkage and degron not mapped
    • Single-cell-type system
  6. 2021 High

    Defined a linkage-specific positive signaling role: K11-linked ubiquitination of TAB1 at three lysines to drive TAK1-dependent NF-κB/MAPK and inflammatory responses in vivo.

    Evidence Knockout/transgenic mice, lysine-mutant ubiquitination assays, septic shock model

    PMID:34017102

    Open questions at the time
    • Did not reconcile the inflammation-promoting role with prior IRF3-degrading and TRAF-modulating roles
  7. 2021 High

    Opened the cancer-substrate phase by identifying ZEB1, SLC7A11, and SOX2 as TRIM26 targets, and revealing a RING-independent stabilizing mechanism for SOX2.

    Evidence Co-IP, ubiquitination assays, domain mutants, USP39 antagonism, patient-derived GSC lines, xenografts

    PMID:33649471 PMID:33869196 PMID:34732716

    Open questions at the time
    • Why TRIM26 degrades some substrates but shields SOX2 from a competing ligase is mechanistically unresolved
  8. 2021 High

    Showed TRIM26 can be exploited by viruses, using K27-linked ubiquitination of HCV NS5B to support viral replication, with species-specific specificity.

    Evidence Genome-wide CRISPR screen, Co-IP, site mapping, cross-species mutagenesis

    PMID:33523994

    Open questions at the time
    • Whether host substrates are co-opted in the same manner not addressed
  9. 2022 Medium

    Demonstrated divergent virus outcomes: TRIM26 SPRY-mediated K48 degradation of HBx and PRRSV-N restricts those viruses, expanding the antiviral substrate range.

    Evidence Co-IP, domain deletion mutants, ubiquitination assays in Huh7 and porcine macrophages

    PMID:35077707 PMID:35872575

    Open questions at the time
    • NLS-independence of PRRSV-N restriction contrasts with NLS-dependent IRF3 degradation, mechanism unexplained
  10. 2022 Medium

    Placed TRIM26 genetically upstream of multiple BER glycosylases (NEIL1/3, OGG1) via epistasis, consolidating its role as a master regulator of glycosylase abundance.

    Evidence siRNA double-knockdown epistasis, survival and repair-kinetics assays under oxidative/X-ray stress

    PMID:36232914

    Open questions at the time
    • Did not establish direct ubiquitination of OGG1/NEIL3
    • Indirect (epistatic) genetic evidence only
  11. 2023 High

    Uncovered a substrate-stabilizing linkage switch: TRIM26 RING-mediated K63 ubiquitination of GPX4 at K107/K117 enhances GPX4 stability and ferroptosis resistance, regulated by PLK1 phosphorylation of TRIM26 at S127.

    Evidence Co-IP, GPX4 site mutants, linkage analysis, phosphorylation inhibition, in vivo tumor models

    PMID:37872147

    Open questions at the time
    • What determines K48-versus-K63 linkage choice across substrates not defined
    • PLK1 input not tested for other substrates
  12. 2023 Medium

    Expanded the degradative cancer-substrate catalogue (RACK1, PBX1, β-catenin) and revealed contradictory HBc handling, where TRIM26 shields rather than degrades the substrate.

    Evidence Co-IP, MS, RING-deletion mutants, proteasome-inhibitor rescue, ubiquitination assays

    PMID:36707504 PMID:37324936 PMID:37591850 PMID:37604854

    Open questions at the time
    • Mechanism by which TRIM26 inhibits HBc ubiquitination rather than catalyzing it is unexplained
    • Single-lab Co-IPs without reconstitution
  13. 2024 Medium

    Established TRIM26 as a broad node in immunometabolism and tissue homeostasis through new substrates (ETK, HSP-90β, NR4A1) and an autophagy route (MAVS via NDP52), with cell-type-specific in vivo phenotypes.

    Evidence Co-IP, CHX chase, knockout mice, AAV rescue, bone-marrow transplant, infection and regeneration models

    PMID:38038978 PMID:38166150 PMID:38773612 PMID:38926362 PMID:38965634 PMID:40490503 PMID:41746668

    Open questions at the time
    • Whether one ligase activity or distinct regulatory inputs select among this many substrates in a given cell is unresolved
    • Several substrate findings rest on single-lab Co-IP plus rescue
  14. 2026 Medium

    Further diversified the substrate network into chromatin and metabolism (NKRF, EZH2, CBX6, LDHA, PKM, UBQLN2) and clarified transcriptional control by E2F3, while showing TRIM26 can both promote and inhibit TRAF6 ubiquitination in different contexts.

    Evidence Co-IP, IP-MS, APEX2 proximity labeling, lysine-mutant ubiquitination, knockout mice, xenografts

    PMID:40449810 PMID:41582437 PMID:41627629 PMID:41652078 PMID:41691946 PMID:42026030 PMID:42088415 PMID:42163428

    Open questions at the time
    • Opposing effects on TRAF6 ubiquitination across studies not mechanistically reconciled
    • Most substrate links are individual single-lab reports

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what governs TRIM26's choice of ubiquitin linkage type (K48 versus K63 versus K11) and degradative-versus-stabilizing outcome across its many substrates, and how its subcellular localization and post-translational regulation route it to immune, repair, or metabolic substrate pools in a given cell.
  • No unifying biochemical determinant of linkage specificity identified
  • No structural model of substrate selection by the PRY/SPRY domain
  • Cross-tissue regulation of substrate access not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0031386 protein tag activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 1 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3
Partners
GPX4IRF3MAVSNEMOSOX2TAB1TBK1TRAF6

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 TRIM26 binds nuclear IRF3 and promotes its K48-linked polyubiquitination and proteasomal degradation, specifically targeting phosphorylated/activated IRF3 (IRF3-5D degraded, IRF3-5A not degraded). TRIM26 undergoes nuclear translocation upon virus infection, which is required for IRF3 degradation. NLS-mutant IRF3 that cannot enter the nucleus is not degraded by TRIM26. Co-immunoprecipitation, ubiquitination assays, nuclear fractionation, IRF3 mutant analysis, TRIM26 transgenic mice, reporter assays PLoS pathogens High 25763818
2015 TRIM26 physically associates with TBK1 independent of viral infection, undergoes autoubiquitination upon RNA virus infection, and the ubiquitinated TRIM26 bridges TBK1-NEMO interaction by associating with NEMO, thereby recruiting TBK1 to the VISA signalsome and activating TBK1 to promote IRF3 and NF-κB activation. Co-immunoprecipitation, knockdown experiments, ubiquitination assays, reporter assays Journal of molecular cell biology Medium 26611359
2016 TRIM26 polyubiquitylates the DNA glycosylase NEIL1 in vitro, targeting the same C-terminal lysine residues as Mule. siRNA knockdown of TRIM26 stabilizes NEIL1 protein levels; stabilization of NEIL1 following TRIM26 knockdown confers cellular resistance to ionising radiation. In vitro ubiquitylation assay with purified proteins, siRNA knockdown, protein stability assays Nucleic acids research High 27924031
2018 TRIM26 ubiquitylates the DNA glycosylase NTH1 predominantly on lysine 67 in vitro. A K67R ubiquitylation-deficient NTH1 mutant is more stable in cells. TRIM26 siRNA knockdown causes exacerbated NTH1 accumulation on chromatin and accelerated DNA damage repair kinetics under oxidative stress. In vitro ubiquitylation assay, site-directed mutagenesis (K67R NTH1 mutant), siRNA knockdown, chromatin fractionation Molecular and cellular biology High 29610152
2018 TGF-β stimulates transcription of TRIM26, which ubiquitylates TAF7 (a TFIID subunit) and targets it for proteasomal degradation, thereby mediating TGF-β-induced proliferative arrest. MYC inhibits TRIM26 induction by TGF-β, enabling recovery from growth arrest. Transcriptional induction assay, co-immunoprecipitation, ubiquitination assays, proliferation assays in cultured mouse mammary epithelial cells Molecular and cellular biology Medium 29203640
2021 TRIM26 catalyzes K11-linked polyubiquitination of TAB1 at Lys294, Lys319, and Lys335, enhancing TAK1 activation and downstream NF-κB and MAPK signaling. Trim26-knockout mice show impaired TAK1 activation and reduced proinflammatory cytokine production upon LPS, TNF-α, and IL-1β stimulation, and are protected from LPS-induced septic shock. Trim26 knockout and transgenic mice, ubiquitination assays with specific lysine mutants, kinase activation assays, LPS-induced septic shock model Cell death and differentiation High 34017102
2021 TRIM26 acts as E3 ubiquitin ligase for ZEB1, promoting its ubiquitination and proteasomal degradation. USP39 deubiquitinase directly interacts with TRIM26 and counteracts TRIM26-mediated ZEB1 ubiquitination in an antagonistic (not competitive) pattern, balancing ZEB1 stability to regulate HCC cell proliferation and migration. Co-immunoprecipitation, immunofluorescence co-localization, ubiquitination assays, loss-of-function and gain-of-function experiments Cell death and differentiation Medium 33649471
2021 TRIM26 physically interacts with SLC7A11 and mediates its ubiquitination, leading to SLC7A11 degradation. TRIM26 overexpression induces ferroptosis in hepatic stellate cells and mitigates CCl4-induced liver fibrosis in mice. Co-immunoprecipitation, ubiquitination assays, in vitro cell assays, in vivo CCl4 mouse model Frontiers in cell and developmental biology Medium 33869196
2021 TRIM26 interacts with the HCV NS5B protein and mediates K27-linked ubiquitination of NS5B at residue K51, promoting NS5B-NS5A interaction and thereby supporting HCV genome replication. Mouse TRIM26 fails to support HCV replication due to a unique six-amino acid insert that prevents interaction with NS5B. Genome-wide CRISPR-Cas9 screen, co-immunoprecipitation, ubiquitination assays, species-specific mutant analysis Science advances High 33523994
2021 TRIM26 stabilizes SOX2 protein in glioblastoma stem cells via its C-terminal PRYSPRY domain, independently of its RING E3 ligase domain, by directly inhibiting the interaction of SOX2 with the E3 ligase WWP2. TRIM26 depletion decreases SOX2 protein levels, increases SOX2 polyubiquitination, disrupts SOX2 gene network, and inhibits self-renewal and in vivo tumorigenicity. Proteomic affinity purification, co-immunoprecipitation, domain deletion mutants, patient-derived glioblastoma stem cell lines, in vivo xenograft Nature communications High 34732716
2022 TRIM26 inhibits HBV replication by interacting with the HBx protein via its SPRY domain and promoting K48-linked ubiquitination and proteasomal degradation of HBx. IFN treatment increases TRIM26 expression. Co-immunoprecipitation, immunofluorescence, ubiquitination assays, siRNA knockdown and overexpression in Huh7 cells Alimentary pharmacology & therapeutics Medium 35872575
2022 TRIM26 siRNA depletion reduces resistance of cells to X-ray radiation and hydrogen peroxide; this resistance can be reversed by additional knockdown of neil1 or ogg1 (for X-rays) or neil1 or neil3 (for hydrogen peroxide), placing TRIM26 upstream of multiple DNA glycosylases in BER regulation. siRNA knockdown epistasis experiments, cell survival assays, DNA repair kinetics International journal of molecular sciences Medium 36232914
2022 TRIM26 promotes degradation of PRRSV nucleocapsid (N) protein through binding via its C-terminal PRY/SPRY domain. Deletion of either the RING domain or the PRY/SPRY domain abolishes antiviral activity. The antiviral activity is independent of the nuclear localization signal. Co-immunoprecipitation, domain deletion mutants, overexpression and siRNA knockdown in porcine alveolar macrophages Virus research Medium 35077707
2023 TRIM26 directly interacts with GPX4 via its RING domain and catalyzes K63-linked polyubiquitination of GPX4 at K107 and K117, switching GPX4 ubiquitination from K48 to K63 linkage and thus enhancing GPX4 protein stability and ferroptosis resistance. PLK1-mediated S127 phosphorylation of TRIM26 enhances TRIM26-GPX4 interaction; inhibition of this phosphorylation reduces GPX4 K63-ubiquitination and protein levels. Co-immunoprecipitation, domain deletion mutants, site-directed mutagenesis of GPX4 ubiquitination sites, phosphorylation inhibition experiments, in vitro and in vivo tumor models Cell death & disease High 37872147
2023 TRIM26 interacts with RACK1 and promotes its ubiquitination and proteasomal degradation, thereby inactivating MEK/ERK signaling. Overexpression of RACK1 reverses the inhibitory effect of TRIM26 on p-MEK1/2 and p-ERK1/2 in osteosarcoma cells. Co-immunoprecipitation, ubiquitination assays, gain- and loss-of-function experiments, Western blot for pathway activation Cell death & disease Medium 37591850
2023 TRIM26 binds PBX1 and mediates its K48-linked polyubiquitination and proteasomal degradation. The C-terminal RING domain of TRIM26 is required for this activity; RING-deleted TRIM26 loses function toward PBX1. Affinity purification-coupled mass spectrometry, co-immunoprecipitation, ubiquitination assays, RING domain deletion mutant International journal of biological sciences Medium 37324936
2023 TRIM26 directly interacts with HBV core protein (HBc) through its SPRY domain. Unexpectedly, TRIM26 inhibits HBc ubiquitination rather than promoting it; TRIM26 knockdown leads to proteasome-dependent HBc degradation. A RING domain-deleted dominant-negative TRIM26 mutant (TRIM26ΔR) promotes HBc degradation, suggesting HBV exploits TRIM26 to protect HBc from proteasomal clearance. Co-immunoprecipitation, siRNA knockdown, domain deletion mutants, proteasome inhibitor rescue experiments Scientific reports Medium 37604854
2023 USP39 inhibits TRIM26 pre-mRNA splicing and maturation, reducing TRIM26 expression. TRIM26, in turn, ubiquitinates β-catenin to promote its degradation. Thus USP39 promotes HCC progression both by direct deubiquitination of β-catenin and by suppressing TRIM26-mediated β-catenin ubiquitination. Co-immunoprecipitation, ubiquitination assays, mRNA splicing analysis, functional knockdown/overexpression Cell death & disease Medium 36707504
2024 TRIM26 promotes autophagic degradation of MAVS through NDP52-mediated selective autophagy. TRIM26 physically associates with MAVS independent of viral infection and reduces its expression; NDP52 interacts with both TRIM26 and MAVS, and TRIM26-induced MAVS degradation is almost entirely blocked in NDP52-knockdown cells. Co-immunoprecipitation, siRNA knockdown, autophagy inhibition assays, PRV infection model Veterinary research Medium 38965634
2024 TRIM26 interacts with HSP-90β and promotes its K48-linked polyubiquitination and proteasomal degradation. This leads to reduced EphA2 protein integrity, thereby suppressing EBV infection of nasopharyngeal epithelial cells. Co-immunoprecipitation, ubiquitination assays, EBV infection assays FASEB journal Medium 38038978
2024 TRIM26 interacts with ETK (a non-receptor tyrosine kinase) via co-immunoprecipitation and facilitates its ubiquitination and proteasomal degradation, resulting in deactivation of AKT/mTOR signaling in ccRCC. ETK overexpression counteracts the inhibitory effects of TRIM26. Co-immunoprecipitation, cycloheximide chase, in vivo ubiquitination assays, RNA sequencing, Western blot, xenograft Journal of translational medicine Medium 38773612
2024 TRIM26 deficiency in macrophages promotes liver regeneration by inducing macrophage polarization toward M1 phenotype, which secretes Wnts (including Wnt2) to stimulate hepatocyte proliferation via Wnt/β-catenin signaling. In hepatocytes, TRIM26 knockdown directly reduces β-catenin ubiquitination and degradation. Bone marrow transplantation confirmed myeloid-cell TRIM26 is critical for this effect. Trim26 knockout mice, AAV-mediated overexpression, partial hepatectomy and CCl4 models, bone marrow transplantation, pharmacological inhibition of Wnt/β-catenin (ICG-001), macrophage depletion (clodronate liposomes) Cell death & disease High 38926362
2024 TRIM26 interacts with TRAF2 through its PRY domain and inhibits K63-linked ubiquitination of TRAF2, thereby attenuating NF-κB pathway activation and suppressing M1-like tumor-associated macrophage polarization. TRIM26 knockout in mice reduced colorectal cancer liver metastasis. Co-immunoprecipitation, luciferase reporter assays, Trim26 knockout mice, CRLM mouse models, flow cytometry British journal of cancer Medium 40490503
2024 P2X7R promotes HuR nucleocytoplasmic shuttling in ageing hearts, which increases mRNA stability of TRIM26 and thus TRIM26 protein expression. TRIM26 subsequently mediates NR4A1 ubiquitination and proteasomal degradation, suppressing mitophagy and accelerating cardiac ageing. P2X7R knockout mice, AAV9 cardiac-specific overexpression, transcriptome sequencing, Western blot, NR4A1 ubiquitination assays Clinical and translational medicine Medium 41746668
2024 TRIM26 restricts inflammatory neutrophil infiltration and proinflammatory cytokine/chemokine (CXCL1, CXCL2) production during Candida infection, protecting mice from fungemia-related kidney damage. Trim26-deficient mice show higher parasite burden, more neutrophil infiltration, and higher proinflammatory cytokines. Trim26-deficient mouse model, Candida albicans infection, flow cytometry, cytokine measurement PLoS pathogens Medium 38166150
2025 TRIM26 interacts with PKM and promotes its ubiquitination, as demonstrated by co-IP and IP-MS in human periodontal ligament stem cells. PKM overexpression rescues TRIM26-mediated suppression of osteogenic differentiation. Co-immunoprecipitation, immunoprecipitation-mass spectrometry, ubiquitination assays, epistasis rescue experiments Free radical biology & medicine Low 40449810
2026 TRIM9 and TRIM26 are selectively enriched in the proximity proteome of ALS-linked UBQLN2P497H mutant (not wild-type). Individual knockdown of TRIM26 (or TRIM9) increases the abundance of a C-terminal UBQLN2 fragment, establishing UBQLN2P497H as a substrate for TRIM26-mediated ubiquitination and proteasomal degradation. APEX2 proximity labeling with LC-MS/MS, co-immunoprecipitation, siRNA knockdown, proteasomal inhibitor treatment, fractionation analysis ACS chemical biology Medium 41582437
2026 TRIM26 interacts with NKRF and promotes its K48-linked ubiquitination at Lys411, leading to proteasomal degradation of NKRF. This sustains SNRPD2 expression, enhancing stress granule assembly and contributing to Osimertinib resistance in lung adenocarcinoma. TRIM26 depletion restored NKRF stability and re-sensitized resistant tumors. Co-immunoprecipitation, ubiquitination assays with specific lysine mutant, TRIM26 genetic depletion, xenograft models Cell death & disease Medium 42026030
2026 TRIM26 interacts with EZH2 and inhibits TRAF6-mediated K48-linked ubiquitination and degradation of EZH2, thereby maintaining EZH2 stability. EZH2 suppresses STAT1 transcriptional activity by catalyzing H3K27me3 modification on the STAT1 gene promoter. TRIM26 deficiency leads to EZH2 degradation, STAT1 upregulation, exacerbated M1 macrophage polarization, and liver fibrosis. Co-immunoprecipitation, ubiquitination assays, Trim26 knockout mice, AAV-mediated restoration, CCl4/BDL fibrosis models, chromatin modification analysis Hepatology international Medium 41627629
2026 TRIM26 directly binds CBX6 and mediates its ubiquitination and degradation. Loss of CBX6 derepresses CNPY2 by eliminating H2AK119ub1 deposition on its promoter, activating NF-κB and IL-8 secretion that recruits neutrophils and induces NET formation in bladder cancer. Co-immunoprecipitation, ubiquitination assays, chromatin modification analysis, functional cancer cell assays, in vivo experiments Drug development research Medium 42163428
2026 TRIM26 directly interacts with and ubiquitinates TRAF6, reducing K48-linked polyubiquitination of TRAF6 to promote cytokine expression during Toxoplasma gondii infection. Trim26-deficient mice show reduced macrophages, inflammatory monocytes, and T cells, along with decreased IL-12, IFN-γ, TNF-α and higher parasite burdens. Co-immunoprecipitation, ubiquitination assays, Trim26 knockout mice, T. gondii infection model, flow cytometry Cellular and molecular life sciences Medium 41652078
2026 E2F3 transcriptionally activates TRIM26 expression. TRIM26 then binds TAB1 via its SPRY domain and promotes K11-linked polyubiquitination via its RING domain, facilitating TAB1-TAK1 complex formation and canonical NF-κB signaling in pancreatic cancer. TRIM26 depletion attenuated E2F3-induced NF-κB activation. ChIP/reporter assays for E2F3→TRIM26 transcription, co-immunoprecipitation, domain deletion mutants, ubiquitination assays, xenograft models International journal of biological sciences Medium 42088415
2026 TRIM26 promotes ubiquitination-mediated degradation of LDHA, as demonstrated by co-immunoprecipitation, cycloheximide chase, and ubiquitination assays. LDHA overexpression reverses TRIM26-mediated suppression of glycolysis and proliferation in endometrial cancer cells. Co-immunoprecipitation, cycloheximide chase, ubiquitination assays, epistasis rescue, xenograft Tissue & cell Medium 41691946
2026 TRIM26 directly interacts with GPX4 and catalyzes its ubiquitination, enhancing GPX4 protein stability in colorectal cancer. TRIM26 knockdown promotes ferroptosis, and GPX4 overexpression rescues the increased ferroptosis caused by sh-TRIM26. Co-immunoprecipitation, ubiquitination assays, ferroptosis inhibitor/inducer experiments, rescue experiments Molecular biology reports Medium 41989643

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 TRIM26 negatively regulates interferon-β production and antiviral response through polyubiquitination and degradation of nuclear IRF3. PLoS pathogens 163 25763818
2021 Deubiquitinase USP39 and E3 ligase TRIM26 balance the level of ZEB1 ubiquitination and thereby determine the progression of hepatocellular carcinoma. Cell death and differentiation 135 33649471
2021 TRIM26 Induces Ferroptosis to Inhibit Hepatic Stellate Cell Activation and Mitigate Liver Fibrosis Through Mediating SLC7A11 Ubiquitination. Frontiers in cell and developmental biology 88 33869196
2023 The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma. Cell death & disease 80 37872147
2015 Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response. Journal of molecular cell biology 72 26611359
2021 TRIM26 positively regulates the inflammatory immune response through K11-linked ubiquitination of TAB1. Cell death and differentiation 63 34017102
1995 Cloning of a new "finger" protein gene (ZNF173) within the class I region of the human MHC. Genomics 55 8530076
2023 USP39 stabilizes β-catenin by deubiquitination and suppressing E3 ligase TRIM26 pre-mRNA maturation to promote HCC progression. Cell death & disease 52 36707504
2021 Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma. Nature communications 52 34732716
2021 TRIM26 is a critical host factor for HCV replication and contributes to host tropism. Science advances 39 33523994
2021 Knockdown of TRIM26 inhibits the proliferation, migration and invasion of bladder cancer cells through the Akt/GSK3β/β-catenin pathway. Chemico-biological interactions 35 33549581
2019 Overexpression of TRIM26 suppresses the proliferation, metastasis, and glycolysis in papillary thyroid carcinoma cells. Journal of cellular physiology 35 30927273
2016 Ubiquitylation-dependent regulation of NEIL1 by Mule and TRIM26 is required for the cellular DNA damage response. Nucleic acids research 33 27924031
2023 TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling. Cell death & disease 24 37591850
2023 TRIM26 promotes non-small cell lung cancer survival by inducing PBX1 degradation. International journal of biological sciences 21 37324936
2022 TRIM26 inhibits hepatitis B virus replication by promoting HBx degradation and TRIM26 genetic polymorphism predicts PegIFNα treatment response of HBeAg-positive chronic hepatitis B Patients. Alimentary pharmacology & therapeutics 20 35872575
2018 A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response. Cancer medicine 20 29956500
2018 NTH1 Is a New Target for Ubiquitylation-Dependent Regulation by TRIM26 Required for the Cellular Response to Oxidative Stress. Molecular and cellular biology 18 29610152
2021 TRIM26 Facilitates HSV-2 Infection by Downregulating Antiviral Responses through the IRF3 Pathway. Viruses 15 33419081
2024 TRIM26 deficiency enhancing liver regeneration through macrophage polarization and β-catenin pathway activation. Cell death & disease 14 38926362
2022 TRIM26-mediated degradation of nucleocapsid protein limits porcine reproductive and respiratory syndrome virus-2 infection. Virus research 14 35077707
1998 BAC/YAC contigs from the H2-M region of mouse Chr 17 define gene order as Znf173-Tctex5-mog-D17Tu42-M3-M2. Immunogenetics 14 9510555
2023 TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein. Scientific reports 12 37604854
2018 Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC. Molecular and cellular biology 12 29203640
2024 TRIM26 facilitates PRV infection through NDP52-mediated autophagic degradation of MAVS. Veterinary research 10 38965634
2024 TRIM26 inhibits clear cell renal cell carcinoma progression through destabilizing ETK and thus inactivation of AKT/mTOR signaling. Journal of translational medicine 8 38773612
2022 TRIM26 Maintains Cell Survival in Response to Oxidative Stress through Regulating DNA Glycosylase Stability. International journal of molecular sciences 8 36232914
2025 TRIM26 deficiency potentially suppresses colorectal cancer liver metastasis through NF-κB-mediated M1-like tumor-associated macrophage polarization. British journal of cancer 7 40490503
2024 TRIM26 restricts Epstein-Barr virus infection in nasopharyngeal epithelial cells through K48-linked ubiquitination of HSP-90β. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 7 38038978
2025 Evodiamine induces ferroptosis in prostate cancer cells by inhibiting TRIM26-mediated stabilization of GPX4. Chinese medicine 6 40420092
2024 TRIM26 alleviates fatal immunopathology by regulating inflammatory neutrophil infiltration during Candida infection. PLoS pathogens 6 38166150
2024 The Multifunction of TRIM26: From Immune Regulation to Oncology. Protein and peptide letters 6 38956921
2025 M2 macrophage-derived exosome facilitates aerobic glycolysis and osteogenic differentiation of hPDLSCs by regulating TRIM26-induced PKM ubiquitination. Free radical biology & medicine 5 40449810
2012 Association study between TRIM26 polymorphisms and risk of aspirin-exacerbated respiratory disease. International journal of molecular medicine 4 22294275
2024 Targeting TRIM26: Unveiling an Oncogene and Identification of Plant Metabolites as a Potential Therapeutics for Breast Cancer. Journal of cellular biochemistry 3 39286999
2024 TRIM26 exacerbates pathological cardiac hypertrophy by activating TAK1. Heliyon 3 39811317
2025 TRIM26 as a dual regulator of ferroptosis and chemoresistance in gastric cancer through HSF1 ubiquitination and exosomal miR-24-3p signaling. Translational oncology 2 40782605
2024 Mechanistic Role of TRIM26 in Viral Infection and Host Defense. Genes 2 39596676
2026 TRIM26 deficiency drives gastric cancer lymph node metastasis via TGF-β signaling activation and modulates gemcitabine response. Frontiers in cell and developmental biology 1 41727323
2025 Inhibition of the PI3K/AKT signaling pathway blocks the oncogenic activity of TRIM26 in prostate cancer cells. Asian journal of andrology 1 40625052
2026 TRIM9 and TRIM26 Interact with UBQLN2P497H to Modulate Its Proteasomal Degradation. ACS chemical biology 0 41582437
2026 TRIM26 deficiency promotes liver fibrosis progression by mediating macrophage polarization via the EZH2-STAT1 axis. Hepatology international 0 41627629
2026 TRIM26-mediated regulation of TRAF6 ubiquitination enhances host immune response during Toxoplasma gondii infection. Cellular and molecular life sciences : CMLS 0 41652078
2026 Paeonol inhibits the progression of endometrial cancer by affecting TRIM26-mediated LDHA ubiquitination modification. Tissue & cell 0 41691946
2026 P2X7R deficiency alleviates cardiac senescence by enhancing mitophagy via the HuR/TRIM26/NR4A1 axis. Clinical and translational medicine 0 41746668
2026 Aberrant expression of TRIM26 suppresses ferroptosis through regulating GPX4 protein stability in colorectal cancer. Molecular biology reports 0 41989643
2026 TRIM26-mediated NKRF degradation drives Osimertinib resistance through SNRPD2-dependent stress granule formation in lung adenocarcinoma. Cell death & disease 0 42026030
2026 Transcriptomic Analysis Reveals the Role of TRIM26 in Hepatocellular Carcinoma and Its Association With the Wnt/β-catenin Signaling Pathway. Human mutation 0 42040893
2026 E2F3 activates NF-κB signaling through TRIM26 mediated TAB1 ubiquitination in pancreatic cancer. International journal of biological sciences 0 42088415
2026 TRIM26-Mediated CBX6 Ubiquitination Triggers NETosis to Drive Bladder Cancer Tumor Growth via the CNPY2/NF-κB Signaling Pathway. Drug development research 0 42163428
2025 Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26. Open medicine (Warsaw, Poland) 0 40918153
2025 PCDH7 promotes EMT and chemoresistance by stabilizing ZEB1 via inhibition of TRIM26-mediated ubiquitination in lung adenocarcinoma. Biochemical pharmacology 0 41271034

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