Affinage

TRIM26

Tripartite motif-containing protein 26 · UniProt Q12899

Length
539 aa
Mass
62.2 kDa
Annotated
2026-04-28
50 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM26 is an MHC-encoded RING-domain E3 ubiquitin ligase that functions as a versatile regulator of innate immunity, DNA damage repair, ferroptosis, and cell proliferation by ubiquitinating a broad spectrum of substrates through linkage-specific ubiquitin chains. It catalyzes K48-linked polyubiquitination to target substrates for proteasomal degradation, including nuclear IRF3 (terminating IFN-β signaling), the DNA glycosylases NEIL1 and NTH1 (controlling base excision repair capacity), TAF7, ZEB1, HBx, SLC7A11, RACK1, ETK, PBX1, NKRF, and HSF1 (PMID:25763818, PMID:27924031, PMID:29610152, PMID:29203640, PMID:33649471, PMID:35872575, PMID:37591850, PMID:38773612, PMID:37324936, PMID:42026030); it also catalyzes K11-linked ubiquitination of TAB1 to activate TAK1–NF-κB signaling and K63-linked ubiquitination of GPX4 to stabilize it and suppress ferroptosis (PMID:34017102, PMID:37872147). Independent of its RING catalytic activity, TRIM26 uses its PRYSPRY domain to stabilize SOX2 by competitively blocking WWP2-mediated degradation in glioblastoma stem cells and to protect EZH2 from TRAF6-mediated ubiquitination in macrophages (PMID:34732716, PMID:41627629). TRIM26 also undergoes autoubiquitination to bridge TBK1–NEMO interaction during antiviral signaling and is exploited by HCV, which requires TRIM26-mediated K27-linked ubiquitination of NS5B for viral genome replication (PMID:26611359, PMID:33523994).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1995 Low

    Positional cloning from the MHC class I region established TRIM26 as a novel RING-finger protein with coiled-coil and zinc-finger domains, providing the first molecular identification but no functional data.

    Evidence cDNA cloning and sequence analysis from human and mouse MHC genomic loci

    PMID:8530076

    Open questions at the time
    • No functional assays performed
    • Domain annotations were purely predictive
    • No substrates or interactors identified
  2. 2015 High

    The first functional role was established: TRIM26 acts as a negative regulator of type I interferon signaling by ubiquitinating nuclear phosphorylated IRF3 for proteasomal degradation, and separately facilitates TBK1-NEMO complex assembly through autoubiquitination, revealing dual and seemingly opposing roles in antiviral innate immunity.

    Evidence Co-IP with mutant IRF3 constructs, TRIM26 transgenic mice with viral infection (IRF3 degradation); siRNA knockdown and reporter assays during RNA virus infection (TBK1-NEMO bridging)

    PMID:25763818 PMID:26611359

    Open questions at the time
    • How TRIM26 balances IRF3 degradation versus TBK1 activation in the same cell remains unclear
    • Autoubiquitination linkage type not specified
  3. 2016 High

    TRIM26 was shown to control DNA damage repair by ubiquitinating the base excision repair glycosylase NEIL1 for proteasomal degradation, establishing it as a regulator of genomic integrity beyond innate immunity.

    Evidence In vitro reconstituted ubiquitylation with purified proteins; siRNA knockdown with ionizing radiation survival assay

    PMID:27924031

    Open questions at the time
    • Whether TRIM26 targets other BER enzymes was unknown at this point
    • Specific ubiquitination sites on NEIL1 not mapped
  4. 2018 High

    The BER regulatory role was deepened by identifying NTH1 as a second glycosylase substrate with ubiquitination site mapping (K67), and TRIM26 was connected to TGF-β signaling through ubiquitination-dependent degradation of the TFIID subunit TAF7, broadening the substrate repertoire to transcriptional regulation.

    Evidence In vitro ubiquitylation with K67R mutagenesis and chromatin fractionation (NTH1); co-IP and siRNA with proliferation assays and MYC epistasis (TAF7)

    PMID:29203640 PMID:29610152

    Open questions at the time
    • Whether TRIM26 targets additional TFIID subunits is unknown
    • How TGF-β-induced TRIM26 transcription is regulated was not resolved
  5. 2021 High

    A burst of studies massively expanded the substrate repertoire and established linkage-type specificity: K11-linked ubiquitination of TAB1 activates TAK1-NF-κB (validated in KO mice); K48-linked ubiquitination targets ZEB1 and SLC7A11 for degradation; K27-linked ubiquitination of HCV NS5B promotes viral replication; and a RING-independent PRYSPRY-mediated mechanism stabilizes SOX2 by blocking WWP2, demonstrating that TRIM26 can both destroy and protect substrates through distinct domains.

    Evidence TAB1 lysine mutagenesis with Trim26-KO mice in LPS/DSS models; co-IP and ubiquitination assays in HCC cells (ZEB1) and hepatic stellate cells (SLC7A11); genome-wide CRISPR screen with species-swap experiments (HCV NS5B); proteomic affinity purification with domain-deletion mutants in GSCs (SOX2)

    PMID:33523994 PMID:33649471 PMID:33869196 PMID:34017102 PMID:34732716

    Open questions at the time
    • How substrate selectivity among K11/K27/K48/K63 linkages is determined remains unknown
    • Whether the PRYSPRY-mediated protective mechanism operates beyond SOX2 was not tested
    • Mouse TRIM26 six-amino-acid insert preventing NS5B interaction was not structurally characterized
  6. 2022 Medium

    TRIM26 was established as a broad BER regulator controlling not just NEIL1 and NTH1 but also OGG1 and NEIL3 levels, and separately shown to restrict HBV replication by degrading HBx through K48-linked ubiquitination via its SPRY domain.

    Evidence Double siRNA knockdowns with radiation/H2O2 survival assays (BER glycosylases); co-IP with domain deletion and viral replication assays in hepatocytes (HBx)

    PMID:35872575 PMID:36232914

    Open questions at the time
    • Direct ubiquitination of OGG1 and NEIL3 by TRIM26 not reconstituted in vitro
    • Whether TRIM26-mediated HBx degradation occurs in patient-derived hepatocytes is untested
  7. 2023 High

    Linkage-type switching was demonstrated: TRIM26 catalyzes K63-linked ubiquitination of GPX4 at K107/K117, stabilizing it and suppressing ferroptosis, with PLK1 phosphorylation of TRIM26 at S127 enhancing this interaction — establishing a phosphorylation-dependent regulatory switch. Additional degradation substrates RACK1, PBX1, NKRF, and HBV core protein were identified.

    Evidence K63R/K48R ubiquitin mutants and GPX4 lysine mutagenesis with PLK1 kinase assay in glioma models; co-IP and ubiquitination assays with rescue experiments for RACK1 (osteosarcoma), PBX1 (AP-MS), and NKRF (K411R mutant, xenografts); RING-independent SPRY domain mapping for HBc

    PMID:37324936 PMID:37591850 PMID:37604854 PMID:37872147 PMID:42026030

    Open questions at the time
    • Structural basis for how TRIM26 switches between K48 and K63 linkage specificity is unknown
    • PLK1-TRIM26 axis not validated in non-glioma contexts
    • NKRF ubiquitination site validation limited to a single mutant
  8. 2024 Medium

    TRIM26 was linked to selective autophagy (degrading MAVS via NDP52 rather than the proteasome), to modulation of TRAF2 K63-ubiquitination affecting macrophage polarization, and to degradation of additional substrates (HSP-90β, ETK, NR4A1, β-catenin), revealing context-dependent degradation pathways and expanding its role to cardiac aging and liver regeneration.

    Evidence NDP52 knockdown rescue of MAVS degradation; TRAF2 PRY domain mapping with KO mouse colorectal metastasis model; co-IP/ubiquitination assays for HSP-90β (EBV entry), ETK (ccRCC), NR4A1 (cardiac aging); partial hepatectomy and CCl4 in Trim26-KO mice (liver regeneration)

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

    Open questions at the time
    • Whether MAVS autophagy-mediated degradation requires TRIM26 E3 ligase activity is untested
    • Direct ubiquitination of β-catenin by TRIM26 not formally demonstrated with reconstituted system
    • NR4A1 ubiquitination by TRIM26 not validated with site mapping
  9. 2025 Medium

    The substrate repertoire continued to expand to metabolic enzymes: TRIM26 degrades LDHA and PKM to suppress glycolysis, and NKRF degradation was linked to stress granule formation and drug resistance, while TRIM26 was identified as an E3 for ALS-linked UBQLN2P497H aggregates.

    Evidence Co-IP and ubiquitination assays with LDHA/PKM rescue experiments; APEX2 proximity labeling with knockdown and fractionation for UBQLN2

    PMID:40449810 PMID:41582437 PMID:41691946

    Open questions at the time
    • Specific ubiquitination sites on LDHA and PKM not mapped
    • Whether TRIM26 degrades wild-type UBQLN2 or is specific to the P497H mutant is unclear
    • In vivo relevance of TRIM26-mediated glycolytic enzyme degradation not demonstrated
  10. 2026 Medium

    TRIM26 was shown to stabilize EZH2 by blocking TRAF6-mediated degradation (RING-independent), and separately to stabilize TRAF6 during parasitic infection, revealing that the same E3 ligase can either promote or prevent ubiquitination of TRAF6 depending on cellular context.

    Evidence Co-IP and ubiquitination assays with Trim26-KO mice in liver fibrosis (EZH2-TRAF6) and Toxoplasma infection (TRAF6 stabilization) models; GPX4 stabilization confirmed in colorectal cancer

    PMID:41627629 PMID:41652078 PMID:41989643

    Open questions at the time
    • How TRIM26 switches between promoting and inhibiting TRAF6 ubiquitination in different contexts is mechanistically unresolved
    • No structural data for any TRIM26-substrate complex
    • Whether TRIM26 directly ubiquitinates TRAF6 or acts indirectly through competition is not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis for TRIM26's remarkable substrate promiscuity and linkage-type selectivity (K11, K27, K48, K63); (2) how TRIM26 is directed to promote versus prevent ubiquitination of different substrates; (3) the physiological contexts in which its RING-dependent versus PRYSPRY-dependent activities predominate; and (4) whether post-translational modifications beyond PLK1-mediated S127 phosphorylation regulate substrate selection.
  • No crystal or cryo-EM structure of TRIM26 or any TRIM26-substrate complex
  • No systematic analysis of all ubiquitin linkage types across substrates
  • No unbiased ubiquitinome analysis in TRIM26-KO cells

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 17 GO:0016874 ligase activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 12 R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-73894 DNA Repair 3
Partners
EZH2GPX4IRF3NEMOSOX2TAB1TRAF2TRAF6

Evidence

Reading pass · 33 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, thereby terminating IFN-β production. TRIM26 degrades phosphorylated/active IRF3 but not the phosphorylation-deficient mutant IRF3-5A, and IRF3 with a mutated NLS (unable to enter nucleus) is not degraded, demonstrating that nuclear localization of both proteins is required. Virus infection promotes TRIM26 nuclear translocation. Co-IP, ubiquitination assays, mutant IRF3 constructs, TRIM26 transgenic mice, viral infection models PLoS pathogens High 25763818
2015 Upon RNA virus infection, TRIM26 undergoes autoubiquitination and the ubiquitinated form associates with NEMO, thereby bridging TBK1-NEMO interaction and facilitating TBK1 recruitment to the VISA signalosome and TBK1 activation for IRF3 and NF-κB signaling. Co-IP, siRNA knockdown, reporter assays, viral infection models Journal of molecular cell biology Medium 26611359
2016 TRIM26 polyubiquitylates the DNA glycosylase NEIL1 in vitro, targeting it for proteasomal degradation. siRNA-mediated knockdown of TRIM26 stabilizes NEIL1, and NEIL1 stabilization following TRIM26 depletion enhances cellular resistance to ionizing radiation. In vitro ubiquitylation assay with purified proteins, siRNA knockdown, cell-based stability assays Nucleic acids research High 27924031
2018 TRIM26 ubiquitylates NTH1 (endonuclease III-like protein 1) predominantly at lysine 67, targeting it for proteasomal degradation. A K67R ubiquitylation-deficient NTH1 mutant is more stable. TRIM26 depletion causes NTH1 accumulation on chromatin and accelerates DNA damage repair, conferring cellular resistance to oxidative stress. In vitro ubiquitylation assay, site-directed mutagenesis (K67R), siRNA knockdown, chromatin fractionation, cell viability assays Molecular and cellular biology High 29610152
2018 TGF-β stimulates transcription of TRIM26, which then ubiquitylates the TFIID subunit TAF7 and targets it for proteasomal degradation, mediating TGF-β-induced proliferative arrest. MYC antagonizes this by inhibiting TRIM26 induction. Ubiquitylation assay, co-IP, siRNA knockdown, cell proliferation assays, MYC overexpression Molecular and cellular biology Medium 29203640
2021 TRIM26 promotes 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 are protected from LPS-induced septic shock and DSS-induced colitis. Ubiquitination assays, site-directed mutagenesis of TAB1 lysines, Trim26-KO and transgenic mice, LPS/DSS in vivo models Cell death and differentiation High 34017102
2021 TRIM26 acts as a direct E3 ubiquitin ligase for ZEB1, promoting its ubiquitination and degradation, thereby inhibiting HCC cell proliferation and migration. The deubiquitinase USP39 antagonizes TRIM26-mediated ZEB1 ubiquitination by directly interacting with TRIM26. Co-IP, immunofluorescence co-localization, ubiquitination assays, siRNA/overexpression in HCC cells Cell death and differentiation Medium 33649471
2021 TRIM26 physically interacts with SLC7A11 (xCT) and mediates its ubiquitination-dependent degradation, thereby promoting lipid peroxidation and ferroptosis in hepatic stellate cells, which suppresses liver fibrosis in vivo. Co-IP, ubiquitination assays, overexpression/KO in HSCs, CCl4 mouse model Frontiers in cell and developmental biology Medium 33869196
2021 TRIM26 interacts with HCV NS5B protein and mediates K27-linked ubiquitination at residue K51, promoting NS5B-NS5A interaction and HCV genome replication. Mouse TRIM26 has a unique six-amino acid insert that prevents its interaction with NS5B, explaining host tropism. Genome-wide CRISPR-Cas9 screen, co-IP, ubiquitination assays, site-directed mutagenesis, species-swap experiments Science advances High 33523994
2021 TRIM26, via its C-terminal PRYSPRY domain but independent of its RING domain, stabilizes SOX2 protein in glioblastoma stem cells by competitively inhibiting the interaction of SOX2 with the E3 ligase WWP2 (a bona fide SOX2 E3 ligase), thereby suppressing SOX2 polyubiquitination. Proteomic affinity purification, co-IP, domain-deletion mutants, GSC self-renewal and tumorigenicity assays Nature communications High 34732716
2021 TRIM26 facilitates HSV-2 replication in vaginal epithelial cells by promoting IRF3 nuclear exclusion, reducing IFN-β production and ISG expression. TRIM26-KO cells show elevated nuclear IRF3 and strongly upregulated IFN-β, MX1, and ISG15. TRIM26 overexpression and CRISPR-KO cell lines, viral titer measurement, immunofluorescence of IRF3 localization, ISG quantification Viruses Medium 33419081
2022 TRIM26 inhibits HBV replication by interacting with HBx via its SPRY domain and promoting K48-linked ubiquitination and proteasomal degradation of HBx. IFN treatment increases TRIM26 expression. Co-IP, immunofluorescence, ubiquitination assay, domain-deletion analysis, siRNA/overexpression in hepatocytes Alimentary pharmacology & therapeutics Medium 35872575
2022 TRIM26 controls cellular levels of multiple DNA glycosylases (NEIL1, NTH1, OGG1, NEIL3) involved in base excision repair. siRNA knockdown of specific glycosylases after TRIM26 depletion reverses radiation/H2O2 resistance, demonstrating TRIM26 as a central regulator balancing BER enzyme levels. siRNA double knockdowns, X-ray/H2O2 cell survival assays, DNA repair kinetics International journal of molecular sciences Medium 36232914
2023 TRIM26 directly interacts with GPX4 through its RING domain and catalyzes K63-linked ubiquitination of GPX4 at K107 and K117, switching GPX4 from K48- to K63-linked polyubiquitination and enhancing GPX4 protein stability, thereby suppressing ferroptosis. PLK1-mediated phosphorylation of TRIM26 at S127 enhances the TRIM26-GPX4 interaction. Co-IP, ubiquitination assays with K63R/K48R mutants, site-directed mutagenesis of GPX4 and TRIM26, domain-deletion analysis, PLK1 kinase assay Cell death & disease High 37872147
2023 TRIM26 interacts with and promotes K48-linked polyubiquitination and proteasomal degradation of PBX1 transcription factor; this activity requires the RING domain. TRIM26-mediated PBX1 degradation inhibits PBX1 transcriptional activity and downstream RNF6 expression. Affinity purification-MS/MS, co-IP, ubiquitination assays, RING domain deletion, reporter assays International journal of biological sciences Medium 37324936
2023 TRIM26 interacts with and promotes ubiquitination-dependent proteasomal degradation of RACK1, thereby inactivating MEK/ERK signaling and inhibiting osteosarcoma progression. RACK1 overexpression rescues the inhibitory effect of TRIM26 overexpression on MEK/ERK. Co-IP, ubiquitination assays, gain- and loss-of-function experiments, MEK/ERK pathway readouts Cell death & disease Medium 37591850
2023 TRIM26 inhibits HBV replication by a RING-domain-independent mechanism: TRIM26 interacts with HBV core protein (HBc) through its SPRY domain and prevents proteasome-dependent HBc degradation, thus acting as a proviral factor for HBc stability. Co-IP, siRNA knockdown, proteasome inhibitor rescue, RING-domain-deleted dominant-negative mutant Scientific reports Medium 37604854
2023 USP39 inhibits TRIM26 pre-mRNA maturation and splicing, reducing TRIM26 protein levels, and thereby indirectly promotes β-catenin stability in HCC, in addition to directly deubiquitinating β-catenin. qRT-PCR, Western blot, mRNA splicing analysis, siRNA knockdown, co-localization Cell death & disease Low 36707504
2024 TRIM26 degrades MAVS through NDP52-mediated selective autophagy (not the proteasome): TRIM26 associates with MAVS independently of viral infection, and NDP52 interacts with both TRIM26 and MAVS. TRIM26-induced MAVS degradation is abolished when NDP52 is knocked down. Co-IP, siRNA knockdown of NDP52, autophagy flux assays, overexpression studies Veterinary research Medium 38965634
2024 TRIM26 interacts with HSP-90β via its E3 ligase activity and promotes K48-linked polyubiquitination and proteasomal degradation of HSP-90β, leading to reduced EphA2 surface expression and suppression of EBV entry into nasopharyngeal epithelial cells. Co-IP, ubiquitination assays, EphA2 stability assays, EBV infection assays FASEB journal Medium 38038978
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 macrophage polarization in colorectal cancer liver metastasis. Co-IP, luciferase reporter assays, domain-deletion (PRY domain), ubiquitination assays, KO mouse CRLM model British journal of cancer Medium 40490503
2024 TRIM26 interacts with ETK (a non-receptor tyrosine kinase) and promotes its K48-linked ubiquitination and proteasomal degradation, inactivating AKT/mTOR signaling and suppressing clear cell renal cell carcinoma progression. Co-IP, CHX chase, in vivo ubiquitination assay, RNA-seq, gain/loss-of-function with rescue by ETK overexpression Journal of translational medicine Medium 38773612
2024 P2X7R promotes HuR nucleocytoplasmic shuttling in ageing hearts, increasing TRIM26 mRNA stability and expression; TRIM26 then mediates NR4A1 ubiquitination and proteasomal degradation, suppressing mitophagy and accelerating cardiac ageing. AAV9-mediated cardiac overexpression, KO mice, Western blot, transcriptome sequencing Clinical and translational medicine Medium 41746668
2024 TRIM26 deficiency promotes liver regeneration by facilitating macrophage polarization toward M1 phenotype, leading to secretion of Wnt2 that activates hepatocyte Wnt/β-catenin signaling. Additionally, TRIM26 knockdown in hepatocytes reduces ubiquitination and degradation of β-catenin, further enhancing Wnt/β-catenin signaling. Partial hepatectomy and CCl4 models in Trim26-KO and AAV-OE mice, bone marrow transplantation, clodronate liposome macrophage depletion, ICG-001 pathway inhibition Cell death & disease Medium 38926362
2025 TRIM26 interacts with NKRF and promotes its K48-linked ubiquitination at Lys411, leading to proteasomal degradation, which sustains SNRPD2 expression and stress granule formation, driving Osimertinib resistance in lung adenocarcinoma. Co-IP, ubiquitination assay with K411R mutant, TRIM26 genetic depletion, xenograft models Cell death & disease Medium 42026030
2025 TRIM26 mediates ubiquitination and proteasomal degradation of PKM (pyruvate kinase M), negatively regulating aerobic glycolysis and osteogenic differentiation; Co-IP confirmed a direct TRIM26-PKM interaction. Co-IP, IP-MS (identifying 410 interacting proteins), ubiquitination assay, overexpression/knockdown with PKM rescue Free radical biology & medicine Low 40449810
2025 TRIM26 mediates ubiquitination and degradation of LDHA in endometrial cancer cells, inhibiting glycolysis; LDHA overexpression reverses the tumor-suppressive effects of TRIM26 overexpression. Co-IP, CHX chase, ubiquitination assay, gain/loss-of-function with LDHA rescue Tissue & cell Low 41691946
2026 TRIM9 and TRIM26 are selectively enriched in the proximity proteome of ALS-linked UBQLN2P497H and coaccumulate with it in the insoluble fraction. Individual knockdown of TRIM26 (or TRIM9) significantly increases abundance of a C-terminal UBQLN2 fragment, establishing UBQLN2P497H as a substrate for TRIM26-mediated ubiquitination and proteasomal degradation. APEX2 proximity labeling, LC-MS/MS, co-IP, Western blot, fractionation, siRNA knockdown, proteasome inhibitor ACS chemical biology Medium 41582437
2026 TRIM26 interacts with EZH2 and inhibits TRAF6-mediated K48-linked ubiquitination and degradation of EZH2, maintaining EZH2 stability. EZH2 in turn suppresses STAT1 transcription via H3K27me3, restraining M1 macrophage polarization and liver fibrosis. Co-IP, ubiquitination assay, Trim26-KO mice, CCl4/BDL liver fibrosis models, AAV-mediated rescue, transcriptomic analysis Hepatology international Medium 41627629
2026 TRIM26 reduces K48-linked polyubiquitination of TRAF6, promoting TRAF6 stability and downstream cytokine expression in macrophages during Toxoplasma gondii infection. Trim26-KO mice show impaired macrophage and T-cell responses and higher parasite burdens. Co-IP, ubiquitination assays, Trim26-KO mice, flow cytometry, in vivo infection model Cellular and molecular life sciences Medium 41652078
2026 TRIM26 promotes ferroptosis resistance in colorectal cancer by directly interacting with GPX4 and catalyzing its ubiquitination, enhancing GPX4 protein stability. GPX4 overexpression rescues the enhanced ferroptosis caused by TRIM26 knockdown. Co-IP, ubiquitination assay, ferroptosis inhibitor/inducer experiments, GPX4 rescue overexpression Molecular biology reports Medium 41989643
2026 TRIM26 mediates K48-linked ubiquitination of HSF1, targeting it for proteasomal degradation and reducing GSH levels while elevating ROS/MDA, thereby inducing ferroptosis and suppressing chemoresistance in gastric cancer. Co-IP, ubiquitination assay, overexpression/knockdown, ferroptosis marker quantification Translational oncology Low 40782605
1995 Positional cloning from the MHC class I region identified TRIM26 (then called ZNF173/AFP) as a protein containing two C3HC4 RING-finger-like zinc-finger domains, a coiled-coil dimerization domain, and a polyglutamic acid region; the gene is expressed in multiple tissues and is conserved between mouse and human. Positional cloning, cDNA isolation, sequence analysis Genomics Low 8530076

Source papers

Stage 0 corpus · 50 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 162 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 127 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 86 33869196
2023 The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma. Cell death & disease 76 37872147
2015 Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response. Journal of molecular cell biology 71 26611359
2021 TRIM26 positively regulates the inflammatory immune response through K11-linked ubiquitination of TAB1. Cell death and differentiation 59 34017102
1995 Cloning of a new "finger" protein gene (ZNF173) within the class I region of the human MHC. Genomics 55 8530076
2021 Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma. Nature communications 51 34732716
2023 USP39 stabilizes β-catenin by deubiquitination and suppressing E3 ligase TRIM26 pre-mRNA maturation to promote HCC progression. Cell death & disease 46 36707504
2021 TRIM26 is a critical host factor for HCV replication and contributes to host tropism. Science advances 38 33523994
2019 Overexpression of TRIM26 suppresses the proliferation, metastasis, and glycolysis in papillary thyroid carcinoma cells. Journal of cellular physiology 34 30927273
2016 Ubiquitylation-dependent regulation of NEIL1 by Mule and TRIM26 is required for the cellular DNA damage response. Nucleic acids research 33 27924031
2021 Knockdown of TRIM26 inhibits the proliferation, migration and invasion of bladder cancer cells through the Akt/GSK3β/β-catenin pathway. Chemico-biological interactions 31 33549581
2023 TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling. Cell death & disease 23 37591850
2023 TRIM26 promotes non-small cell lung cancer survival by inducing PBX1 degradation. International journal of biological sciences 20 37324936
2018 A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response. Cancer medicine 20 29956500
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 19 35872575
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
2022 TRIM26-mediated degradation of nucleocapsid protein limits porcine reproductive and respiratory syndrome virus-2 infection. Virus research 14 35077707
2021 TRIM26 Facilitates HSV-2 Infection by Downregulating Antiviral Responses through the IRF3 Pathway. Viruses 14 33419081
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
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
2023 TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein. Scientific reports 10 37604854
2024 TRIM26 deficiency enhancing liver regeneration through macrophage polarization and β-catenin pathway activation. Cell death & disease 9 38926362
2022 TRIM26 Maintains Cell Survival in Response to Oxidative Stress through Regulating DNA Glycosylase Stability. International journal of molecular sciences 8 36232914
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
2024 TRIM26 inhibits clear cell renal cell carcinoma progression through destabilizing ETK and thus inactivation of AKT/mTOR signaling. Journal of translational medicine 7 38773612
2024 TRIM26 alleviates fatal immunopathology by regulating inflammatory neutrophil infiltration during Candida infection. PLoS pathogens 5 38166150
2024 The Multifunction of TRIM26: From Immune Regulation to Oncology. Protein and peptide letters 4 38956921
2012 Association study between TRIM26 polymorphisms and risk of aspirin-exacerbated respiratory disease. International journal of molecular medicine 4 22294275
2025 Evodiamine induces ferroptosis in prostate cancer cells by inhibiting TRIM26-mediated stabilization of GPX4. Chinese medicine 3 40420092
2025 M2 macrophage-derived exosome facilitates aerobic glycolysis and osteogenic differentiation of hPDLSCs by regulating TRIM26-induced PKM ubiquitination. Free radical biology & medicine 3 40449810
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 deficiency potentially suppresses colorectal cancer liver metastasis through NF-κB-mediated M1-like tumor-associated macrophage polarization. British journal of cancer 2 40490503
2024 Mechanistic Role of TRIM26 in Viral Infection and Host Defense. Genes 2 39596676
2025 Inhibition of the PI3K/AKT signaling pathway blocks the oncogenic activity of TRIM26 in prostate cancer cells. Asian journal of andrology 1 40625052
2025 TRIM26 as a dual regulator of ferroptosis and chemoresistance in gastric cancer through HSF1 ubiquitination and exosomal miR-24-3p signaling. Translational oncology 1 40782605
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 TRIM26 deficiency drives gastric cancer lymph node metastasis via TGF-β signaling activation and modulates gemcitabine response. Frontiers in cell and developmental biology 0 41727323
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
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