Affinage

TRIM8

E3 ubiquitin-protein ligase TRIM8 · UniProt Q9BZR9

Length
551 aa
Mass
61.5 kDa
Annotated
2026-06-10
74 papers in source corpus 30 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM8 is a RING finger E3 ubiquitin ligase of the RBCC/TRIM family that governs protein stability across innate immune, transcriptional, and cell-cycle programs by directing substrate-selective polyubiquitination (PMID:11118312, PMID:34329586). In innate immunity it acts bidirectionally: it potentiates NF-κB signaling by mediating K63-linked polyubiquitination of the kinase TAK1, with cytoplasmic translocation of TRIM8 required for this activation (PMID:22084099, PMID:23152791); conversely it restrains TLR3/TLR4 responses by catalyzing K6/K33-linked ubiquitination of TRIF to disrupt the TRIF-TBK1 association, and Trim8-knockout mice show heightened susceptibility to endotoxin and Salmonella (PMID:28747347). TRIM8 also reinforces STAT3-dependent signaling by ubiquitinating and degrading the STAT3 inhibitor PIAS3, forming a positive feedback loop that sustains glioblastoma stem-cell self-renewal, and modulates phospho-STAT3 nuclear transport through Hsp90β (PMID:20516148, PMID:28100038, PMID:21689689). Through physical interaction with p53 it impairs the p53-MDM2 association, drives MDM2 degradation, and stabilizes p53 to enforce cell-cycle arrest, while itself being a p53-induced gene (PMID:22262183). The bulk of its characterized targets are degraded via K48-linked polyubiquitination—including the EWS/FLI fusion oncoprotein (making TRIM8 a selective dependency in Ewing sarcoma), HNF4α (recruited by TRIB3 during NAFLD), ERα, VDAC2, MYOF, YTHDF2, GPX1, SOCS1, and CAPN2—linking TRIM8 to oncogenic protein turnover, ferroptosis, and antioxidant defense (PMID:34329586, PMID:38237865, PMID:33163282, PMID:38881325, PMID:39934162, PMID:40073810, PMID:35968584, PMID:38918306, PMID:40520022). A non-catalytic mode also exists: in plasmacytoid dendritic cells TRIM8 protects phospho-IRF7 from Pin1-mediated proteasomal destruction in an E3-independent manner to enable type I IFN production (PMID:31799391). TRIM8 localizes to nuclear bodies in a C-terminus-dependent manner and to the mitotic spindle and centrosome/ciliary base, where it interacts with KIF11/Eg5 and KIFC1 to control centrosome separation, spindle bipolarity, chromosomal stability, and ciliogenesis (PMID:33508234, PMID:31904480, PMID:41057298). De novo C-terminal truncating variants mislocalize TRIM8 from nuclear bodies to diffuse nucleoplasm, defining a human disease mechanism affecting podocyte and neuronal function (PMID:33508234).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 Medium

    Established TRIM8 as a regulator of cytokine signaling by showing it destabilizes a key negative regulator, the first functional readout for the protein.

    Evidence Reciprocal Co-IP in vitro and in vivo plus co-expression functional assay showing TRIM8 decreases SOCS-1 stability and relieves IFN-γ repression

    PMID:12163497

    Open questions at the time
    • Ubiquitin-linkage type not defined
    • RING-dependence of SOCS-1 turnover not established in this study
  2. 2010 Medium

    Defined a STAT3-promoting mode by identifying PIAS3 as a TRIM8 target whose loss enhances STAT3 signaling and supports transformation.

    Evidence Co-IP, proteasome-pathway assays, nuclear/cytoplasmic fractionation, and focus-formation assay in NIH3T3 cells

    PMID:20516148

    Open questions at the time
    • Whether regulation is degradation versus nuclear exclusion left ambiguous
    • Ubiquitin-linkage specificity not resolved
  3. 2011 High

    Identified the catalytic basis for TRIM8's NF-κB activation by showing K63-linked ubiquitination of the upstream kinase TAK1.

    Evidence Co-IP, K63-specific ubiquitination assay, and overexpression/knockdown with NF-κB reporters

    PMID:22084099

    Open questions at the time
    • Ubiquitin acceptor lysines on TAK1 not mapped
    • Signal-dependent regulation of TRIM8 activity not defined here
  4. 2012 Medium

    Connected TRIM8 to the p53 tumor-suppressor axis, showing it stabilizes p53 by degrading MDM2 and is itself a p53 stress-response target.

    Evidence Co-IP, Western blot for MDM2 degradation, cell-cycle analysis, and qRT-PCR of p53 targets after UV stress

    PMID:22262183

    Open questions at the time
    • Direct MDM2 ubiquitination by TRIM8 not demonstrated
    • Linkage type on MDM2 unknown
  5. 2012 Medium

    Showed that subcellular relocation gates TRIM8 function, with TNF-induced nuclear-to-cytoplasmic translocation required for NF-κB activation.

    Evidence Live GFP-TRIM8 imaging, domain-mutant analysis, fractionation, and NF-κB reporters

    PMID:23152791

    Open questions at the time
    • Trigger and machinery for translocation unknown
    • Relationship to TAK1 ubiquitination not integrated
  6. 2017 High

    Resolved a context-dependent immune role: TRIM8 negatively regulates TLR3/4 signaling by atypical K6/K33 ubiquitination of TRIF, validated by knockout-mouse phenotypes.

    Evidence Trim8-knockout mice, Co-IP, K6/K33-specific ubiquitination assays, and in vivo infection/inflammation models

    PMID:28747347

    Open questions at the time
    • How TRIM8 switches between NF-κB activation and TLR restraint not defined
    • TRIF acceptor lysines not mapped
  7. 2017 Medium

    Placed TRIM8 in cancer stemness through a STAT3-PIAS3 positive feedback loop sustaining glioblastoma stem-like cells.

    Evidence TRIM8 KD/OE, Western blots for p-STAT3/PIAS3/stemness markers, sphere-forming assays, and immunoprecipitation

    PMID:28100038

    Open questions at the time
    • PIAS3 ubiquitin-linkage type not specified
    • Generality beyond GSCs untested in this study
  8. 2017 Medium

    Extended the p53 network by showing TRIM8 lowers pro-proliferative ΔNp63α in a reciprocal negative feedback loop.

    Evidence Western blot of ΔNp63α, proteasome and caspase-1 inhibitor assays, and TRIM8 promoter luciferase reporter

    PMID:31781486

    Open questions at the time
    • Direct ubiquitination of ΔNp63α not shown
    • Role of caspase-1 versus proteasome not fully separated
  9. 2018 Medium

    Revealed a cytoprotective role linking TRIM8 to autophagy and apoptosis control during genotoxic stress.

    Evidence LC3-turnover autophagy flux assays, Co-IP of a TRIM8-XIAP-caspase-3 complex, and etoposide treatment with KD/OE

    PMID:29678622

    Open questions at the time
    • Whether TRIM8 ubiquitinates XIAP or caspase-3 directly unclear
    • Mechanism of lysosomal/autophagy regulation undefined
  10. 2019 High

    Uncovered an E3-independent function: TRIM8 shields phospho-IRF7 from Pin1-driven degradation to license type I IFN in pDCs.

    Evidence siRNA screen in primary human pDCs, Co-IP with Pin1, and proteasomal degradation assays

    PMID:31799391

    Open questions at the time
    • Structural basis of pIRF7 protection not defined
    • Whether the RING is dispensable in other contexts unknown
  11. 2020 Medium

    Defined a mitotic structural role, placing TRIM8 at the spindle/centrosome through interactions with spindle motors and linking it to chromosomal stability.

    Evidence Interactome proteomics in neural stem cells, Co-IP with KIF11/KIFC1, mitotic immunofluorescence, and KD cell-cycle analysis

    PMID:31904480

    Open questions at the time
    • Whether spindle regulation requires E3 activity unknown
    • Motor substrates of TRIM8 ubiquitination not identified
  12. 2020 Medium

    Linked TRIM8 to neurodevelopment and schizophrenia risk via promoter regulation by POU3F2 and effects on neural progenitor differentiation.

    Evidence Luciferase reporter, EMSA at SNP rs5011218, TRIM8 KD in NPCs, and mEPSC electrophysiology

    PMID:32929213

    Open questions at the time
    • Downstream TRIM8 effectors in neurons not identified
    • Single-lab functional readouts
  13. 2021 High

    Identified TRIM8 as a selective Ewing sarcoma dependency by degrading the EWS/FLI fusion oncoprotein to prevent oncogene overdose.

    Evidence CRISPR-Cas9 screen, TRIM8 knockout, ubiquitination and protein-stability assays, and rescue experiments

    PMID:34329586

    Open questions at the time
    • EWS/FLI ubiquitin acceptor sites not mapped
    • Generalizability to other fusion oncoproteins untested
  14. 2021 Medium

    Established the human disease mechanism by showing C-terminal truncating variants mislocalize TRIM8 from nuclear bodies to diffuse nucleoplasm.

    Evidence Overexpression of WT and patient-variant constructs in podocytes and neuronal cells with co-localization microscopy

    PMID:33508234

    Open questions at the time
    • Functional consequence of mislocalization on substrate ubiquitination not measured
    • Nuclear-body composition incompletely defined
  15. 2023 Medium

    Showed TRIM8 participates in reciprocal E3-E3 cross-regulation, being degraded by and degrading TRIM21 in cancer cells.

    Evidence Reciprocal Co-IP and K48-specific ubiquitination assays with KD/OE in lung and renal cancer cells

    PMID:37914816

    Open questions at the time
    • Physiological trigger for the mutual degradation unknown
    • Single-lab observation
  16. 2024 High

    Demonstrated adaptor-directed substrate selection, with TRIB3 recruiting TRIM8 to degrade HNF4α via site-specific K48 ubiquitination during NAFLD.

    Evidence Co-IP/MS, in vitro and in vivo ubiquitination assays, and K470 site-specific mutagenesis

    PMID:38237865

    Open questions at the time
    • Whether other adaptors redirect TRIM8 substrate choice unknown
    • Regulation of TRIB3-TRIM8 complex assembly undefined
  17. 2024 Medium

    Broadened the K48-degradation substrate set into cancer metabolism and ferroptosis (VDAC2, SOCS1) supporting tumor cell survival and proliferation.

    Evidence Co-IP/MS, ubiquitination assays, functional rescue, and xenograft models across ovarian and cervical cancer

    PMID:38881325 PMID:38918306

    Open questions at the time
    • Acceptor lysines not mapped
    • Context-specificity of substrate engagement unclear
  18. 2025 Medium

    Consolidated TRIM8 as a broad K48-ligase across antiviral defense and disease (PEDV N protein, MYOF, YTHDF2, GPX1, CAPN2) and as a K63-ligase promoting PGK1-driven glycolytic angiogenesis.

    Evidence Co-IP with domain mapping, linkage-specific ubiquitination assays, and in vivo/functional models across multiple tissues

    PMID:35968584 PMID:39819815 PMID:39934162 PMID:40073810 PMID:40520022 PMID:41184227

    Open questions at the time
    • Determinants of K48-versus-K63 linkage choice across substrates undefined
    • Most substrates established by single labs
  19. 2025 Medium

    Refined the mitotic/ciliary localization by placing endogenous TRIM8 with CEP170 at the centrosome throughout mitosis and linking depletion to ciliogenesis defects and TOP2A regulation.

    Evidence scRNA-seq, LC-MS/MS proteomics, polysome profiling, immunofluorescence, and KD in ARPE-19 cells

    PMID:41057298

    Open questions at the time
    • Whether ciliary function requires ubiquitin ligase activity unknown
    • Direct ciliary substrates not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIM8 selects among its many K48 versus K63 substrates and switches between catalytic and E3-independent (e.g. pIRF7-protective) modes, and how C-terminal condensate/nuclear-body integrity controls these activities, remain unresolved.
  • No unifying model for linkage-type or substrate selection
  • Structural basis of condensate formation and its functional output undefined
  • In vivo hierarchy among competing substrate pathways unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016740 transferase activity 9 GO:0016874 ligase activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1 GO:0005929 cilium 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
EWS/FLIHNF4ΑKIF11P53PIAS3PIN1TAK1TRIF
Complex memberships
TRIB3-TRIM8-HNF4α E3 ligase complexTRIM8-XIAP-caspase-3 complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 TRIM8/GERP (also known as RNF27) physically interacts with SOCS-1 in vitro and in vivo, and co-expression of TRIM8 with SOCS-1 decreases SOCS-1 protein stability and levels, resulting in decreased repression of interferon-gamma signaling by SOCS-1. Co-immunoprecipitation (in vitro and in vivo), co-expression functional assay The Journal of biological chemistry Medium 12163497
2000 TRIM8/GERP contains an N-terminal RING finger, two B-boxes, and a coiled-coil domain, placing it in the RBCC subfamily of RING finger proteins, and is expressed in brain, lung, breast, placenta, kidney, muscle, and germinal center B cells. cDNA cloning, sequence analysis, expression profiling by PCR Biochemical and biophysical research communications Medium 11118312
2010 TRIM8 interacts with PIAS3 (protein inhibitor of activated STAT3) and negatively regulates PIAS3 either by proteasomal degradation or by excluding PIAS3 from the nucleus, thereby enhancing STAT3-dependent signaling. Ectopic TRIM8 expression in NIH3T3 cells enhances Src-dependent tumorigenesis. Co-immunoprecipitation, ubiquitin-proteasome pathway assays, nuclear/cytoplasmic fractionation, focus formation assay Journal of cell science Medium 20516148
2011 TRIM8 mediates K63-linked polyubiquitination of TAK1, a serine/threonine kinase essential for TNFα- and IL-1β-induced NF-κB activation. TRIM8 interacts with TAK1 and its overexpression potentiates NF-κB activation, while knockdown has opposite effects. Co-immunoprecipitation, ubiquitination assay (K63-specific), overexpression and knockdown with NF-κB reporter assays Proceedings of the National Academy of Sciences of the United States of America High 22084099
2011 TRIM8 interacts with Hsp90β, which in turn interacts with STAT3, and TRIM8 modulates nuclear translocation of phosphorylated STAT3 through this interaction, thereby selectively downregulating Nanog transcription in embryonic stem cells. TRIM8 knockdown increased nuclear phospho-STAT3 and enhanced Nanog transcription. Co-immunoprecipitation, knockdown, nuclear fractionation, qPCR for Nanog Biochimica et biophysica acta Medium 21689689
2012 TRIM8 physically interacts with p53 (by co-immunoprecipitation), impairs p53 interaction with MDM2, induces degradation of MDM2, and stabilizes p53, leading to cell cycle arrest and upregulation of CDKN1A (p21) and GADD45. TRIM8 expression is induced by p53 under stress conditions (UV exposure). Co-immunoprecipitation, Western blot, cell cycle analysis, gene expression assays (qRT-PCR), TRIM8 knockdown/overexpression Cell cycle (Georgetown, Tex.) Medium 22262183
2012 TRIM8 undergoes TNF-induced translocation from the nucleus to the cytoplasm, and this cytoplasmic translocation is essential for TNF-induced NF-κB activation (but not p65-mediated NF-κB). TRIM8 negates PIAS3-mediated negative repression of NF-κB at p65 by inducing PIAS3 translocation from nucleus to cytoplasm and its turnover. TRIM8 ubiquitin ligase activity is required for regulation of NF-κB in both cytoplasm and nucleus. Fluorescence microscopy (live imaging of GFP-TRIM8), domain mutant analysis, nuclear/cytoplasmic fractionation, NF-κB reporter assays PloS one Medium 23152791
2017 TRIM8 negatively regulates TLR3- and TLR4-mediated innate immune responses by interacting with TRIF (TOLL/IL-1 receptor domain-containing adapter-inducing IFN-β) and mediating K6- and K33-linked polyubiquitination of TRIF, leading to disruption of the TRIF-TBK1 association. TRIM8-knockout mice showed increased susceptibility to poly I:C- and LPS-induced inflammatory death and Salmonella infection. Trim8 gene-knockout mouse model, co-immunoprecipitation, K6/K33-specific ubiquitination assays, cytokine measurements, in vivo infection models Journal of immunology (Baltimore, Md. : 1950) High 28747347
2017 TRIM8 activates STAT3 signaling to maintain stemness and self-renewal of glioblastoma stem-like cells (GSCs) by suppressing PIAS3 expression through E3-mediated ubiquitination and proteasomal degradation. STAT3 activation also upregulates TRIM8, forming a positive feedback loop. TRIM8 knockdown and overexpression, Western blot for p-STAT3/PIAS3/stemness markers, sphere-forming assays, immunoprecipitation Molecular oncology Medium 28100038
2017 TRIM8 reduces levels of the pro-proliferative ΔNp63α protein in both a proteasomal and caspase-1 dependent manner in a p53 wild-type background. ΔNp63α in turn suppresses TRIM8 gene expression by preventing p53-mediated transactivation of TRIM8, forming a negative feedback loop. Western blot for ΔNp63α degradation, proteasomal and caspase-1 inhibitor assays, TRIM8 overexpression, luciferase reporter for TRIM8 promoter Frontiers in oncology Medium 31781486
2019 TRIM8 protects phosphorylated IRF7 (pIRF7) from proteasomal degradation in human plasmacytoid dendritic cells in an E3 ubiquitin ligase-independent manner by preventing its recognition by the peptidyl-prolyl isomerase Pin1, thereby enabling type I IFN production. siRNA screen in primary human pDCs, TRIM8 knockdown, co-immunoprecipitation with Pin1, proteasomal degradation assays Science advances High 31799391
2019 TRIM8 regulates lysosomal biogenesis and autophagy flux. TRIM8 stabilizes XIAP during genotoxic stress and forms a complex with XIAP and caspase-3 to inhibit caspase-3 activation. TRIM8-mediated autophagy promotes degradation of cleaved caspase-3 subunits, providing cytoprotection during genotoxic stress. Autophagy flux assays (LC3 turnover), co-immunoprecipitation (TRIM8-XIAP-caspase-3 complex), TRIM8 overexpression/knockdown, etoposide treatment Cellular signalling Medium 29678622
2020 TRIM8 interacts with KIF11/Eg5 and KIFC1, two master regulators of mitotic spindle assembly, localizes at the mitotic spindle during mitosis, and plays a role in centrosome separation at the beginning of mitosis, with its depletion causing delayed mitotic progression and chromosomal instability. Proteomics/interactome in primary mouse embryonic neural stem cells, co-immunoprecipitation, immunofluorescence microscopy during mitosis, TRIM8 knockdown with cell cycle analysis Cancer letters Medium 31904480
2020 POU3F2 transcription factor directly binds to the SCZ-associated SNP rs5011218 in the TRIM8 promoter region (validated by EMSA and luciferase reporter assay), inducing TRIM8 expression. Knockdown of TRIM8 in human neural progenitor cells promoted proliferation, inhibited neuronal differentiation, and impaired excitatory synaptic transmission. Luciferase reporter assay, EMSA, TRIM8 knockdown in NPCs, electrophysiology (mEPSCs) Molecular psychiatry Medium 32929213
2021 TRIM8 functions as an E3 ubiquitin ligase that ubiquitinates EWS/FLI fusion oncoprotein, leading to its degradation. TRIM8 knockout leads to increased EWS/FLI protein levels that are not tolerated (oncogene overdose), making TRIM8 a selective dependency in Ewing sarcoma. This was discovered via CRISPR-Cas9 screening. CRISPR-Cas9 screen, TRIM8 knockout, ubiquitination assays, protein stability assays, rescue experiments Cancer cell High 34329586
2021 De novo truncating TRIM8 variants cause mislocalization of the TRIM8 protein from nuclear bodies to diffuse nucleoplasm. Wild-type TRIM8 localizes to nuclear bodies that co-localize with Gemini and Cajal bodies in immortalized human podocytes and neuronal cells; all pathogenic truncations cluster within the C-terminal region (residues 390–487) and result in diffuse nucleoplasmic distribution. Overexpression of WT and patient-variant TRIM8 constructs in podocyte and neuronal cell lines, fluorescence microscopy, co-localization studies American journal of human genetics Medium 33508234
2020 TRIM8 acts as a positive regulator of IFN-γ signaling in macrophages; TRIM8 knockdown in cultured macrophages significantly reduced IFN-γ responsiveness. siRNA knockdown in macrophages, IFN-γ signaling readouts (gene expression, phospho-STAT1) Annals of the rheumatic diseases Low 33277241
2020 TRIM8 interacts with ERα via its RING domain in the cytoplasm and increases polyubiquitination of the ERα protein, leading to ERα degradation and suppression of estrogen signaling and breast cancer cell proliferation. Co-immunoprecipitation, domain mapping (RING domain mutant), ubiquitination assay, RNA sequencing, in vitro and in vivo proliferation assays American journal of cancer research Medium 33163282
2024 TRIB3 directly interacts with HNF4α and recruits TRIM8 to form an E3 ligase complex that catalyzes K48-linked polyubiquitination of HNF4α at lysine 470, leading to proteasomal degradation of HNF4α during ER stress and NAFLD progression. Co-immunoprecipitation, mass spectrometry, in vivo and in vitro ubiquitination assays, site-specific mutagenesis (K470), RNA sequencing Journal of hepatology High 38237865
2023 TRIM21 and TRIM8 directly mutually regulate each other via K48-linked ubiquitination, activating the proteasome pathway for each other's degradation in lung and renal cancer cells. Co-immunoprecipitation, K48-specific ubiquitination assays, overexpression/knockdown experiments Oncogene Medium 37914816
2024 TRIM8 interacts with VDAC2 and promotes its K48-linked polyubiquitination and proteasomal degradation, increasing ovarian cancer cell resistance to ferroptosis and promoting proliferation and migration. Co-immunoprecipitation, mass spectrometry, Western blot, ubiquitination assay, xenograft mouse model Cancer medicine Medium 38881325
2025 TRIM8 promotes K63-linked ubiquitination of glycolytic enzyme PGK1, improving PGK1 stability, which leads to ACAT1 recruitment and subsequent PGK1 acetylation-dependent glycolytic activity, facilitating lactate accumulation and tumor angiogenesis in gastric cancer. Co-immunoprecipitation, K63-specific ubiquitination assay, acetylation assays, tube formation and endothelial migration assays Cell death & disease Medium 41184227
2025 TRIM8 facilitates K48-linked ubiquitin-proteasome degradation of YTHDF2 via its RING domain, which inhibits YTHDF2-m6A-mediated SREBF2 mRNA degradation, thereby upregulating SREBF2 and enhancing chondrocyte ferroptosis in osteoarthritis. Co-immunoprecipitation, RING domain mutant, ubiquitination assay, m6A-YTHDF2 pathway assays, TRIM8 KD in OA mouse model International immunopharmacology Medium 40073810
2025 TRIM8 promotes K48-linked ubiquitin-proteasome degradation of the PEDV nucleocapsid (N) protein via interaction with the coiled-coil domain of TRIM8, inhibiting PEDV replication in a dose-dependent manner. Co-immunoprecipitation, TRIM8 knockout/overexpression cell lines, K48-specific ubiquitination assays, TRIM8 domain mapping Veterinary research Medium 39819815
2025 TRIM8 promotes K48-linked ubiquitination of MYOF (myoferlin), facilitating its proteasomal degradation, thereby suppressing extracellular MMP secretion, cell migration, and lung cancer metastasis. Co-immunoprecipitation, K48-specific ubiquitination assay, gain-/loss-of-function experiments, xenograft model Cell death & disease Medium 39934162
2025 Endogenous TRIM8 localizes as a novel ciliary protein co-localizing with CEP170 at the centrosomal region throughout all mitotic phases. TRIM8 depletion results in reduced number of ciliated cells and shorter cilia in ARPE-19 cells, and perturbs the 'Cell Cycle Control of Chromosomal Replication' pathway. TRIM8 negatively regulates TOP2A expression. scRNA-seq, proteomics (LC-MS/MS), polysome profiling with RNA-seq, immunofluorescence microscopy, TRIM8 knockdown Cell death & disease Medium 41057298
2025 Disease-causing C-terminal truncations of TRIM8 disrupt its condensate formation, impair proteasomal regulation, and disrupt TAK1/NF-κB signaling; functional assays in cellular and animal models link these disruptions to podocyte dysfunction and impaired response to injury. Systematic mesoscale localization screen (72 TRIM proteins), condensate formation assays, proteasomal regulation assays, NF-κB signaling assays, podocyte functional models, animal models bioRxivpreprint Medium
2024 TRIM8 ubiquitinates and degrades SOCS1 in cervical cancer cells, promoting cancer cell proliferation, invasion, and migration; inhibition of SOCS1 partially reverses the effects of TRIM8 knockdown. Protein immunoprecipitation, ubiquitination assay (MG132 treatment), CCK-8/colony formation/Transwell assays, rescue experiments with si-SOCS1 Biochemical genetics Medium 38918306
2022 TRIM8 interacts with GPX1 (glutathione peroxidase 1) and promotes GPX1 ubiquitination and degradation, negatively regulating antioxidant defense in cardiomyocytes during ischemia/reperfusion injury. Co-immunoprecipitation, ubiquitination assay, TRIM8 overexpression/knockdown, in vitro I/R model and in vivo rat model Pharmaceutical biology Medium 35968584
2025 ITLN1 antagonizes TRIM8-mediated K48-linked ubiquitination and degradation of CAPN2 (calpain-2) by binding TRIM8, thereby stabilizing CAPN2 and promoting ZBP1-dependent PANoptosis in intestinal epithelial cells in Crohn's disease. Co-immunoprecipitation combined with mass spectrometry, RNA-seq, ubiquitination assays, rescue experiments, IL-10 KO colitis mouse model International journal of biological sciences Medium 40520022
2024 TRIM8 inhibits DUSP14, promoting MAPKs pathway activation, leading to adipocyte inflammation and insulin resistance; TRIM8 deficiency decreased inflammatory cytokines and improved insulin signaling, effects reversed by DUSP14 knockdown. TRIM8 knockdown/overexpression, DUSP14 knockdown/overexpression, cytokine measurements, glucose uptake assay, Western blot for insulin signaling Adipocyte Low 39039652

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Tripartite motif 8 (TRIM8) modulates TNFα- and IL-1β-triggered NF-κB activation by targeting TAK1 for K63-linked polyubiquitination. Proceedings of the National Academy of Sciences of the United States of America 167 22084099
2002 TRIM8/GERP RING finger protein interacts with SOCS-1. The Journal of biological chemistry 98 12163497
2021 TRIM8 modulates the EWS/FLI oncoprotein to promote survival in Ewing sarcoma. Cancer cell 94 34329586
2000 Mutations in the gerP locus of Bacillus subtilis and Bacillus cereus affect access of germinants to their targets in spores. Journal of bacteriology 77 10715007
2010 TRIM8 modulates STAT3 activity through negative regulation of PIAS3. Journal of cell science 74 20516148
2017 TRIM8 restores p53 tumour suppressor function by blunting N-MYC activity in chemo-resistant tumours. Molecular cancer 71 28327152
2017 TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction. Journal of immunology (Baltimore, Md. : 1950) 62 28747347
2012 TRIM8 modulates p53 activity to dictate cell cycle arrest. Cell cycle (Georgetown, Tex.) 60 22262183
2017 TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3. Molecular oncology 59 28100038
2016 Fish TRIM8 exerts antiviral roles through regulation of the proinflammatory factors and interferon signaling. Fish & shellfish immunology 50 27150052
2015 TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival. BMC cancer 49 26077989
2019 TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells. Science advances 48 31799391
2012 Nucleo-cytoplasmic trafficking of TRIM8, a novel oncogene, is involved in positive regulation of TNF induced NF-κB pathway. PloS one 47 23152791
2020 Monocyte and bone marrow macrophage transcriptional phenotypes in systemic juvenile idiopathic arthritis reveal TRIM8 as a mediator of IFN-γ hyper-responsiveness and risk for macrophage activation syndrome. Annals of the rheumatic diseases 45 33277241
2014 TRIM8 anti-proliferative action against chemo-resistant renal cell carcinoma. Oncotarget 43 25277184
2012 Analysis of the effects of a gerP mutation on the germination of spores of Bacillus subtilis. Journal of bacteriology 39 22904285
2020 Inhibition of TRIM8 restrains ischaemia-reperfusion-mediated cerebral injury by regulation of NF-κB activation associated inflammation and apoptosis. Experimental cell research 38 31917201
2024 TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability. Journal of hepatology 37 38237865
2021 Knockdown of TRIM8 Protects HK-2 Cells Against Hypoxia/Reoxygenation-Induced Injury by Inhibiting Oxidative Stress-Mediated Apoptosis and Pyroptosis via PI3K/Akt Signal Pathway. Drug design, development and therapy 37 34916780
2017 Tripartite Motif 8 (TRIM8) Positively Regulates Pro-inflammatory Responses in Pseudomonas aeruginosa-Induced Keratitis Through Promoting K63-Linked Polyubiquitination of TAK1 Protein. Inflammation 37 27995356
2021 Emerging Roles of TRIM8 in Health and Disease. Cells 32 33807506
2000 A novel RING finger-B box-coiled-coil protein, GERP. Biochemical and biophysical research communications 32 11118312
2011 TRIM8 regulates Nanog via Hsp90β-mediated nuclear translocation of STAT3 in embryonic stem cells. Biochimica et biophysica acta 31 21689689
2017 TRIM8: Making the Right Decision between the Oncogene and Tumour Suppressor Role. Genes 30 29182544
2020 Rise of TRIM8: A Molecule of Duality. Molecular therapy. Nucleic acids 29 33230447
2016 De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy. Annals of human genetics 29 27346735
2020 MicroRNA-665-3p attenuates oxygen-glucose deprivation-evoked microglial cell apoptosis and inflammatory response by inhibiting NF-κB signaling via targeting TRIM8. International immunopharmacology 28 32512270
2020 Transcription factor POU3F2 regulates TRIM8 expression contributing to cellular functions implicated in schizophrenia. Molecular psychiatry 26 32929213
2010 Role of the gerP operon in germination and outgrowth of Bacillus anthracis spores. PloS one 26 20161744
2020 TRIM8 inhibits breast cancer proliferation by regulating estrogen signaling. American journal of cancer research 25 33163282
2018 Further delineation of the clinical spectrum of de novo TRIM8 truncating mutations. American journal of medical genetics. Part A 24 30244534
2020 TRIM8 interacts with KIF11 and KIFC1 and controls bipolar spindle formation and chromosomal stability. Cancer letters 23 31904480
2018 TRIM8 regulated autophagy modulates the level of cleaved Caspase-3 subunit to inhibit genotoxic stress induced cell death. Cellular signalling 23 29678622
2021 MicroRNA-665 facilitates cell proliferation and represses apoptosis through modulating Wnt5a/β-Catenin and Caspase-3 signaling pathways by targeting TRIM8 in LUSC. Cancer cell international 22 33858426
2018 TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways. Biochimica et biophysica acta. General subjects 22 30528352
2020 Down-regulation of long noncoding RNA LINC00472 alleviates sepsis-induced acute hepatic injury by regulating miR-373-3p/TRIM8 axis. Experimental and molecular pathology 21 33129786
2021 TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance. Biomedicines 20 33673719
2021 De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis. American journal of human genetics 19 33508234
2019 Downregulation of TRIM8 protects neurons from oxygen-glucose deprivation/re-oxygenation-induced injury through reinforcement of the AMPK/Nrf2/ARE antioxidant signaling pathway. Brain research 17 31862654
2018 Proteins Encoded by the gerP Operon Are Localized to the Inner Coat in Bacillus cereus Spores and Are Dependent on GerPA and SafA for Assembly. Applied and environmental microbiology 17 29728391
2022 Salvianolic acid B inhibits myocardial I/R-induced ROS generation and cell apoptosis by regulating the TRIM8/GPX1 pathway. Pharmaceutical biology 16 35968584
2020 Suppression of TRIM8 by microRNA-182-5p restricts tumor necrosis factor-α-induced proliferation and migration of airway smooth muscle cells through inactivation of NF-Κb. International immunopharmacology 16 32283508
2022 Circular RNA circ_0002594 regulates PDGF-BB-induced proliferation and migration of human airway smooth muscle cells via sponging miR-139-5p/TRIM8 in asthma. Autoimmunity 15 35470728
2022 Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis. Cancers 15 35565438
2023 Mutual regulation between TRIM21 and TRIM8 via K48-linked ubiquitination. Oncogene 14 37914816
2025 ITLN1 exacerbates Crohn's colitis by driving ZBP1-dependent PANoptosis in intestinal epithelial cells through antagonizing TRIM8-mediated CAPN2 ubiquitination. International journal of biological sciences 13 40520022
2020 Association of a de novo nonsense mutation of the TRIM8 gene with childhood-onset focal segmental glomerulosclerosis. Pediatric nephrology (Berlin, Germany) 13 32193649
2020 Knockdown of TRIM8 Attenuates IL-1β-induced Inflammatory Response in Osteoarthritis Chondrocytes Through the Inactivation of NF-κB Pathway. Cell transplantation 12 32757662
2023 TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt. Cellular & molecular biology letters 10 36690946
2020 Focal segmental glomerulosclerosis and mild intellectual disability in a patient with a novel de novo truncating TRIM8 mutation. European journal of medical genetics 10 32531461
2019 TRIM8 Blunts the Pro-proliferative Action of ΔNp63α in a p53 Wild-Type Background. Frontiers in oncology 10 31781486
2021 A novel de novo truncating TRIM8 variant associated with childhood-onset focal segmental glomerulosclerosis without epileptic encephalopathy: a case report. BMC nephrology 9 34930159
2024 Saikosaponin F ameliorates depression-associated dry eye disease by inhibiting TRIM8-induced TAK1 ubiquitination. International immunopharmacology 8 38430804
2024 TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation. Cancer medicine 7 38881325
2024 Inhibiting TRIM8 alleviates adipocyte inflammation and insulin resistance by regulating the DUSP14/MAPKs pathway. Adipocyte 7 39039652
2024 Silencing TRIM8 alleviates allergic asthma and suppressing Th2 differentiation through inhibiting NF-κB/NLRP3 signaling pathway. Immunology letters 5 39260527
2022 Two Children With Steroid-Resistant Significant Proteinuria Due to Nonsense Mutations of the TRIM8 Gene: A Case Report and Literature Review. Frontiers in pediatrics 5 35903163
2023 Diversification processes in Gerp's mouse lemur demonstrate the importance of rivers and altitude as biogeographic barriers in Madagascar's humid rainforests. Ecology and evolution 4 37408627
2025 TRIM8 enhances chondrocyte ferroptosis by inhibiting YTHDF2-m6A mediated SREBF2 mRNA degradation to promote OA progression. International immunopharmacology 3 40073810
2024 Variants loci and phenotype correlation of TRIM8-related neuro-renal syndrome: three cases reports and literature review. Frontiers in neurology 3 39416667
2023 Knockdown of TRIM8 alleviates dextran sulfate sodium-induced colitis in mice by inhibiting the NF-κB signaling pathway. Allergologia et immunopathologia 3 36617827
2023 De novo truncating variants of TRIM8 and atypical neuro-renal syndrome: a case report and literature review. Italian journal of pediatrics 3 37061734
2022 Identification and validation of novel biomarker TRIM8 related to cervical cancer. Frontiers in oncology 3 36353542
2025 E3 ligase TRIM8 suppresses lung cancer metastasis by targeting MYOF degradation through K48-linked polyubiquitination. Cell death & disease 2 39934162
2024 TRIM8 Promotes Proliferation, Invasion, and Migration of Cervical Cancer Cells by Ubiquitinating and Degrading SOCS1. Biochemical genetics 2 38918306
2004 Genomic organization and cytokine-mediated inducibility of the human TRIM-8/Gerp gene. International journal of immunopathology and pharmacology 2 15345195
2025 TRIM8-dependent K63-ubiquitinated PGK1 promotes glycolysis and angiogenesis in gastric cancer via interaction with ACAT1. Cell death & disease 1 41184227
2024 A Rare De Novo Mutation in the TRIM8 Gene in a 17-Year-Old Boy with Steroid-Resistant Nephrotic Syndrome: Case Report. International journal of molecular sciences 1 38674071
2024 Focal segmental glomerulosclerosis and neurogenic bladder in a Chinese patient with a novel de novo pathogenic variation in TRIM8 gene: A case report. SAGE open medical case reports 1 39669799
2025 TRIM8 inhibits porcine epidemic diarrhoea virus replication by targeting and ubiquitinately degrading the nucleocapsid protein. Veterinary research 0 39819815
2025 The dynamic role of TRIM8, a novel ciliary protein, during various stages of mitosis. Cell death & disease 0 41057298
2025 TRIM8-associated non-coding RNA panel as a biomarker for Lupus nephritis activity. Journal of translational medicine 0 41194165
2025 A TRIM8 Variant in a Child: Neuro-Renal Syndrome Causing Features Suggestive of Medullary Sponge Kidney. Nephrology (Carlton, Vic.) 0 41219125
2024 A nonsense mutation in the Tripartite motif containing 8 (TRIM8) gene, mimicking collagenopathy. Pediatric nephrology (Berlin, Germany) 0 39708126

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