Affinage

TRIM65

E3 ubiquitin-protein ligase TRIM65 · UniProt Q6PJ69

Length
517 aa
Mass
57.4 kDa
Annotated
2026-06-10
46 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM65 is a RING domain E3 ubiquitin ligase whose catalytic activity, established by E3-dead and RING-mutant controls (PMID:31310649, PMID:35218667), coordinates antiviral innate immunity, inflammasome restraint, and a broad set of cancer- and metabolism-linked degradation events. In innate immunity it acts as a dual activating switch: it promotes K63-linked ubiquitination of MDA5 at Lys743 to drive MDA5 oligomerization, IRF3 activation, and type I interferon production—selectively for the MDA5 axis and not RIG-I, TLR3, or cGAS (PMID:28031478)—a step that can be amplified by ARRDC4-mediated recruitment of TRIM65 to MDA5 (PMID:28594402), and it further potentiates the interferon response by K6-linked ubiquitination of IRF3 via its BBCC domain, enhancing IRF3 chromatin recruitment to the IFNβ promoter (PMID:39580801). In parallel it restrains inflammation by binding the NLRP3 NACHT domain and catalyzing K48/K63-linked ubiquitination of NLRP3 to block NEK7-NLRP3 assembly and IL-1β secretion (PMID:34512673), and by targeting VCAM-1 for K48-linked degradation in endothelium, limiting LPS-driven pulmonary inflammation and atherosclerosis (PMID:31310649, PMID:37608612). Across non-immune contexts TRIM65 functions predominantly as a degradative ligase that drives proteasomal turnover of diverse substrates—including p53 (PMID:27012201, PMID:35402260), TNRC6/GW182 proteins to relieve miRNA silencing (PMID:24778252, PMID:31160576), NUDT21 to reprogram alternative polyadenylation in renal fibrosis (PMID:38951701), TOX4 (PMID:38212319), BTG3 (PMID:38777825), NF2 (PMID:39005234), and the metabolic regulators AMPK, PDK4, and IREB2 governing glycolysis and ferroptosis (PMID:40748757, PMID:40473847). Its ligase output is itself tuned by post-translational modification, including p300-mediated lactylation at Lys206 that lowers catalytic activity (PMID:40748757). Beyond these defined substrate-specific axes, no unifying structural model linking domain usage to substrate selection has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2014 High

    Established TRIM65 as an E3 ligase coupling the ubiquitin system to miRNA-mediated silencing, the first defined substrate-level mechanism for the protein.

    Evidence Proteomic interactome, Co-IP, ubiquitination and miRNA reporter assays showing TRIM65 degrades TNRC6/GW182 in P-body-like structures

    PMID:24778252

    Open questions at the time
    • Did not map the ubiquitination site on TNRC6
    • Did not define which RING/SPRY elements confer substrate selection
  2. 2016 High

    Defined a non-degradative, activating role for TRIM65 in antiviral signaling, distinguishing it mechanistically from its degradative substrate handling.

    Evidence Co-IP, site-specific K63 ubiquitination mapping at MDA5 Lys743, Trim65 KO mice with pathway-specific loss of MDA5-driven IFN

    PMID:28031478

    Open questions at the time
    • Did not resolve how the same ligase chooses K63 (activating) versus K48 (degradative) linkages on different substrates
  3. 2016 Medium

    Identified p53 as a degradative target, positioning TRIM65 as a pro-proliferative ligase in cancer.

    Evidence Co-IP and ubiquitination assays with cell growth readouts in p53-null comparison

    PMID:27012201

    Open questions at the time
    • No ubiquitination site mapped on p53
    • Relationship to MDM2 not addressed in this study
  4. 2017 Medium

    Showed that ARRDC4 functions as an adaptor recruiting TRIM65 to MDA5, providing a recruitment logic for the antiviral activating step.

    Evidence Co-IP and ubiquitination assays with clinical specimen correlation during EV71 infection

    PMID:28594402

    Open questions at the time
    • Single lab
    • Whether ARRDC4 recruitment is required in vivo not tested
  5. 2018 Medium

    Clarified the p53 mechanism as competition with MDM2 for N-terminal binding, linking TRIM65 to MDM2-inhibitor resistance.

    Evidence Co-IP N-terminus mapping, Nutlin-3a epistasis, TCGA mutual exclusivity analysis

    PMID:30454706

    Open questions at the time
    • Competitive model inferred from binding rather than structural data
    • Single lab
  6. 2021 High

    Established TRIM65 as a negative regulator of the NLRP3 inflammasome, expanding its immune role from interferon induction to inflammation restraint.

    Evidence NACHT-domain binding, dual K48/K63 ubiquitination, KO mice in LPS and MSU models with inflammasome specificity

    PMID:34512673

    Open questions at the time
    • How dual linkage types co-occur on NLRP3 mechanistically unresolved
    • Site of ubiquitination not mapped in this study
  7. 2023 Medium

    Refined the NLRP3 mechanism by mapping the modification site (K285) and showing pharmacological enhancement, linking the axis to neuroinflammation.

    Evidence Site-specific ubiquitination, Co-IP, CUMS mouse model with berberine

    PMID:37595491

    Open questions at the time
    • Single lab
    • Linkage type at K285 not specified
  8. 2024 High

    Demonstrated a second activating step in interferon signaling—K6-linked ubiquitination of IRF3 that boosts its chromatin recruitment—broadening TRIM65's non-degradative repertoire.

    Evidence BBCC-IAD domain mapping, linkage-specific ubiquitination, chromatin recruitment and IFNβ promoter binding assays

    PMID:39580801

    Open questions at the time
    • How K6 chains alter IRF3 chromatin engagement mechanistically not resolved
    • Relationship to the MDA5 step not integrated
  9. 2024 High

    Used unbiased substrate discovery to extend TRIM65 into RNA processing and fibrosis, degrading NUDT21 to reprogram alternative polyadenylation.

    Evidence Yeast two-hybrid, site-specific K48 ubiquitination at NUDT21 Lys56, KO mice, AAV9 in vivo rescue in UUO/folic acid models

    PMID:38951701

    Open questions at the time
    • Why TRIM65 selects NUDT21 in renal tubular cells not defined
    • Tissue-restricted activity not explained mechanistically
  10. 2024 High

    Identified TOX4 as an anti-apoptotic degradation target and mapped the coiled-coil/SPRY domains used for substrate binding.

    Evidence Yeast two-hybrid, domain mapping, K48 ubiquitination, confocal co-localization, KO mice in H/R intestinal injury

    PMID:38212319

    Open questions at the time
    • Whether SPRY-mediated binding generalizes to other substrates untested
  11. 2024 Medium

    Linked TRIM65 to upstream regulation by O-GlcNAcylation and to YAP/Hippo and metabolic reprogramming via NF2 degradation.

    Evidence Site-specific K44 ubiquitination of NF2, OGT-mediated modification, metabolomics in HCC

    PMID:39005234

    Open questions at the time
    • Functional consequence of O-GlcNAcylation on ligase activity not quantified
    • Single lab
  12. 2024 Medium

    Consolidated the cell-cycle role by showing K48-linked degradation of BTG3 at K41 relieving G2/M arrest.

    Evidence Site-specific mutagenesis, Co-IP, cell-cycle analysis, in vivo proliferation in RCC

    PMID:38777825

    Open questions at the time
    • Single lab
    • Tissue specificity of the BTG3 axis unexplored
  13. 2025 High

    Connected TRIM65 to ferroptosis and glycolysis control and uncovered lactylation as a feedback brake on its catalytic activity.

    Evidence KO/overexpression mice in DKD, dual substrate (IREB2, PDK4) identification, p300-lactylation at K206 with K206R mutant rescue

    PMID:40748757

    Open questions at the time
    • Whether lactylation affects all substrates equally not tested
    • Structural basis of K206 lactylation on RING activity unknown
  14. 2025 Medium

    Extended the glycolytic axis to glioma via AMPK degradation relieving HIF-1α-driven aerobic glycolysis.

    Evidence Co-IP, ubiquitination, RNA-seq, AMPK/HIF-1α rescue epistasis, in vivo proliferation

    PMID:40473847

    Open questions at the time
    • Ubiquitination site on AMPK not mapped
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single E3 ligase selects among >20 reported substrates and switches between activating (K63/K6) and degradative (K48) ubiquitin linkages in a tissue- and stimulus-specific manner.
  • No structural model of domain-substrate recognition
  • No unified framework linking PTM state (lactylation, O-GlcNAcylation) to linkage-type output
  • Adaptor requirements beyond ARRDC4 largely unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 1
Partners
ARRDC4IRF3MDA5NLRP3NUDT21TNRC6ATOX4VCAM-1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 TRIM65 specifically interacts with MDA5 and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. Trim65 deficiency abolishes MDA5 agonist- or EMCV-induced IRF3 activation and type I interferon production but has no effect on RIG-I, TLR3, or cGAS signaling pathways. Co-immunoprecipitation, ubiquitination assays, Trim65 knockout mice, in vitro and in vivo infection models The Journal of experimental medicine High 28031478
2014 TRIM65 functions as an E3 ubiquitin ligase for TNRC6 (GW182) proteins; it interacts with and co-localizes with TNRC6 proteins in P-body-like structures, and promotes their ubiquitination and degradation, thereby relieving miRNA-driven suppression of mRNA expression. Proteomic interactome screen, Co-IP, ubiquitination assays, overexpression and RNAi knockdown, miRNA reporter assays, co-localization microscopy Proceedings of the National Academy of Sciences of the United States of America High 24778252
2016 TRIM65 binds to p53 and functions as an E3 ubiquitin ligase toward p53, promoting p53 poly-ubiquitination and proteasome-mediated degradation, thereby inactivating p53 and promoting cell proliferation. Co-immunoprecipitation, ubiquitination assays, overexpression and knockdown studies, cell growth assays, cisplatin induction experiments Biochemical and biophysical research communications Medium 27012201
2017 TRIM65 directly binds to Axin1 and promotes its ubiquitylation and proteasomal degradation, thereby activating the β-catenin signaling pathway and promoting hepatocellular carcinoma cell growth and metastasis. HMGA1 was identified as an upstream transcriptional regulator of TRIM65. Co-immunoprecipitation, ubiquitination assays, overexpression and knockdown, in vitro and in vivo tumor models Journal of cell science Medium 28754688
2018 TRIM65 promotes ubiquitination and degradation of ANXA2, modulating cytoskeleton rearrangement and inducing epithelial-mesenchymal transition in bladder urothelial carcinoma cells. Co-immunoprecipitation, ubiquitination assays, in vitro and in vivo experiments Cancer letters Medium 30075204
2019 TRIM65 mediates ubiquitination and degradation of ARHGAP35, a Rho GTPase-activating protein, leading to elevated Rho GTPase activity and enhanced CRC cell migration via actin cytoskeleton remodeling (focal adhesions and filopodia). Co-immunoprecipitation, ubiquitination assays, overexpression and knockdown, in vivo metastasis models Oncogene Medium 31332286
2020 TRIM65 directly interacts with VCAM-1 and promotes its polyubiquitination and proteasomal degradation in vascular endothelial cells; wild-type TRIM65 but not an E3 ligase-dead mutant promotes VCAM-1 degradation. TRIM65-deficient mice are more sensitive to LPS-induced death due to sustained pulmonary inflammation. Co-immunoprecipitation, ubiquitination assays with E3-dead mutant, siRNA knockdown, TRIM65 knockout mice, LPS model Journal of molecular cell biology High 31310649
2019 TRIM65 promotes ubiquitination and degradation of TNRC6A, resulting in suppressed expression of miR-138-5p, which relieves ATG7 suppression and sustains autophagy in cisplatin-resistant NSCLC cells. Western blot, immunofluorescence, siRNA knockdown, miRNA inhibitor rescue experiments, apoptosis assays Cell death & disease Medium 31160576
2017 ARRDC4 interacts with MDA5 via its arrestin-like N domain and recruits TRIM65 to enhance K63-linked ubiquitination of MDA5, resulting in activation of downstream innate signaling and transcription of proinflammatory cytokines during EV71 infection. Co-immunoprecipitation, ubiquitination assays, overexpression and knockdown, clinical specimen correlation Cell death & disease Medium 28594402
2021 TRIM65 binds to the NACHT domain of NLRP3 and promotes both K48- and K63-linked ubiquitination of NLRP3, restraining NEK7-NLRP3 interaction and thereby inhibiting NLRP3 inflammasome assembly, caspase-1 activation, and IL-1β secretion. TRIM65 deficiency had no effect on AIM2 or IPAF inflammasome activation. Immunoprecipitation, ubiquitination assays, TRIM65 knockout mice, in vivo inflammatory disease models (LPS, monosodium urate) Frontiers in immunology High 34512673
2021 TRIM65 promotes invasion of endometrial stromal cells by ubiquitinating DUSP6, leading to ERK1/2 activation, which then induces C-myc expression. C-myc in turn promotes TRIM65 transcription, forming a positive feedback loop. This axis elevates MMP-2 and integrin β1. Co-immunoprecipitation, ubiquitination assays, dual luciferase assay, chromatin immunoprecipitation, Transwell assay The Journal of clinical endocrinology and metabolism Medium 33146694
2022 TRIM65 directly targets p53 for ubiquitination and proteasomal degradation in cervical cancer cells, promoting autophagy inhibition and reduced apoptosis; TRIM65 knockdown enhanced autophagic flux and apoptosis. Western blot, ubiquitination assays, Co-IP, knockdown studies, autophagic flux assays, apoptosis assays Frontiers in oncology Medium 35402260
2022 TRIM65 promotes ubiquitination and degradation of LATS1 protein, driving TNBC cell proliferation, invasion, and migration. Co-IP, cycloheximide chase, endogenous ubiquitination assay, rescue experiments Oxidative medicine and cellular longevity Medium 36035221
2022 TRIM65 ubiquitinates and degrades TPIT protein at multiple Lys sites in a RING domain-dependent manner, inhibiting POMC transcription and ACTH production in pituitary corticotroph cells. Biochemical analyses, confocal microscopy, luciferase reporter assays, mutagenesis (RING domain), in vitro and in vivo models Neuro-oncology Medium 35218667
2023 TRIM65 promotes ubiquitination and degradation of JAK1, thereby inhibiting the JAK1/STAT1 signaling pathway, reducing ROS production, and attenuating ISO-induced cardiac hypertrophy; TRIM65 KO mice develop more severe hypertrophy with impaired autophagic flux and mitochondrial damage. TRIM65 knockout mice, overexpression, TEM, Stat1 inhibitor rescue, Western blot European journal of pharmacology Medium 37080331
2024 TRIM65 mediates K48-linked polyubiquitination of NUDT21 (CFIm25) at lysine 56 and promotes its proteasomal degradation, leading to altered alternative polyadenylation of pro-fibrotic genes (Col1a1, Fn-1, Tgfbr1, Wnt5a, Fzd2) and activation of TGF-β1/SMAD and ERK1/2 signaling, thereby promoting renal fibrosis. Yeast two-hybrid (substrate identification), Co-IP, ubiquitination assays, AAV9 delivery in vivo, UUO and folic acid mouse models, TRIM65 KO mice Cell death and differentiation High 38951701
2024 TRIM65 mediates ubiquitylation at lysine 44 of NF2 (neurofibromin 2), promoting its degradation, inhibiting YAP1 phosphorylation, and aberrantly activating metabolic enzyme transcription related to uridine nucleotide and fatty acid metabolism in HCC. O-GlcNAcylation of TRIM65 by OGT was identified as an upstream regulatory modification. Co-immunoprecipitation, ubiquitination assays, site-specific mutagenesis (K44), metabolomic analyses, overexpression and knockdown Advanced science Medium 39005234
2024 TRIM65 promotes K48-linked ubiquitination and degradation of BTG3 at K41, relieving G2/M cell cycle arrest and promoting renal cell carcinoma proliferation via the TRIM65-BTG3-CyclinD1 axis. Co-immunoprecipitation, ubiquitination assays, site-specific mutagenesis (K41), cell cycle analysis, in vitro and in vivo proliferation assays, IHC tissue microarray Cell death & disease Medium 38777825
2024 TRIM65 directly binds to TOX4 through its coiled-coil and SPRY domains, co-localizing with TOX4 in both cytoplasm and nucleus, and mediates K48-linked ubiquitination and proteasomal degradation of TOX4 to inhibit intestinal epithelial apoptosis during ischemia/reperfusion injury. Yeast two-hybrid (substrate identification), Co-IP, immunofluorescence confocal microscopy, ubiquitination assays, TRIM65 KO mice, H/R cell model Cell death & disease High 38212319
2024 TRIM65 inhibits HBV replication at the transcriptional level through its E3 ubiquitin ligase activity and intact B-box domain; CRISPR-mediated TRIM65 knockout in HepG2-NTCP cells boosted HBV infection, confirming endogenous antiviral role. Ectopic expression of 45 TRIM proteins, HBV-transfected HepG2 cells, CRISPR knockout, promoter-specific reporter assays, domain mutagenesis (B-box) Viruses Medium 38932182
2024 TRIM65 interacts with IRF3 via its BBCC domain engaging the IAD domain of IRF3, and promotes K6-linked ubiquitination of IRF3, enhancing IRF3 chromatin recruitment and binding to the IFNβ promoter, thereby boosting IFNβ and ISG expression. Co-immunoprecipitation, ubiquitination assays with linkage-specific analysis, domain mapping, chromatin recruitment assays, IFNβ promoter binding assays Cell reports High 39580801
2024 TRIM65 interacts with VCAM-1 and targets it for K48-linked ubiquitination in endothelial cells; TRIM65 knockout in ApoE-/- mice results in elevated VCAM-1 levels and increased atherosclerotic plaque development. Co-immunoprecipitation, Western blot, siRNA knockdown, TRIM65/ApoE double-KO mice, immunofluorescence Current medicinal chemistry Medium 37608612
2025 TRIM65 suppresses ferroptosis by targeting IREB2 for ubiquitin-mediated degradation and inhibits glycolysis through ubiquitination and degradation of pyruvate dehydrogenase kinase 4 (PDK4). Lactate promotes p300-mediated lactylation of TRIM65 at K206, which reduces its ubiquitin ligase activity; the lactylation-defective K206R mutant shows enhanced protective effects against diabetic kidney disease. TRIM65 KO and TEC-specific overexpression mice, DKD models, site-specific mutagenesis (K206R), Co-IP, ubiquitination assays, ferroptosis and glycolysis functional assays Cell reports High 40748757
2025 TRIM65 promotes K48-linked ubiquitination and degradation of AMPK, thereby relieving AMPK-mediated suppression of HIF-1α-induced glycolysis and promoting glioma cell proliferation and aerobic glycolysis (Warburg effect). Co-immunoprecipitation, ubiquitination assays, RNA sequencing, AMPK and HIF-1α knockdown/overexpression rescue, in vitro and in vivo proliferation assays NPJ precision oncology Medium 40473847
2025 TRIM65 directly interacts with ALOX5 and promotes its ubiquitination and degradation, inhibiting H/R-induced cardiomyocyte apoptosis, inflammation, and ferroptosis; sevoflurane activates TRIM65-mediated ubiquitination of ALOX5 to alleviate myocardial ischemia/reperfusion injury. Co-IP, ubiquitination assays, overexpression and knockdown, H/R cell model, MI/R rat model, Western blot Applied biochemistry and biotechnology Medium 41182544
2022 TRIM65 knockdown inhibits proliferation and invasion of gastric cancer cells by preventing ubiquitin-mediated degradation of PPM1A, resulting in reduced phosphorylation of TBK1. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, CCK-8, colony formation, Transwell assay, Western blot Experimental cell research Medium 35421368
2023 TRIM65 promotes ubiquitination of NLRP3 at K285 in hippocampal neurons; berberine enhances TRIM65-NLRP3 binding and NLRP3 ubiquitination, suppressing NLRP3 inflammasome activity and exerting antidepressant effects. Western blot, ELISA, ubiquitination assays, immunoprecipitation, CUMS mouse model, siRNA knockdown International immunopharmacology Medium 37595491
2018 TRIM65 binds to the N-terminus of p53 and competes with MDM2 for p53 binding; overexpression of TRIM65 renders lung cancer cells resistant to Nutlin-3a (MDM2 inhibitor), and combined depletion of TRIM65 with Nutlin-3a shows enhanced anti-tumor effects. Co-immunoprecipitation (N-terminus mapping), cell proliferation assays, p53 activation assays, siRNA knockdown combined with Nutlin-3a, TCGA mutual exclusivity analysis Biochemical and biophysical research communications Medium 30454706
2024 TRIM65 and WWP1 are induced downstream of a PAI-1-c-Myc signaling cascade in renal tubular cells; silencing of TRIM65 attenuates PAI-1-induced fibrotic signaling and epithelial dedifferentiation. Restoration of BMP-7/SMAD5 disrupts c-Myc induction and reduces TRIM65/WWP1 upregulation. siRNA knockdown, BMP-7/SMAD5 restoration, Western blot, primary human renal epithelial cells and HK-2 cells Biomolecules Low 41897310

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 TRIM65-catalized ubiquitination is essential for MDA5-mediated antiviral innate immunity. The Journal of experimental medicine 154 28031478
2019 Knockdown of TRIM65 inhibits autophagy and cisplatin resistance in A549/DDP cells by regulating miR-138-5p/ATG7. Cell death & disease 132 31160576
2014 TRIM65 regulates microRNA activity by ubiquitination of TNRC6. Proceedings of the National Academy of Sciences of the United States of America 69 24778252
2018 TRIM65 supports bladder urothelial carcinoma cell aggressiveness by promoting ANXA2 ubiquitination and degradation. Cancer letters 67 30075204
2017 TRIM65 triggers β-catenin signaling via ubiquitylation of Axin1 to promote hepatocellular carcinoma. Journal of cell science 57 28754688
2019 Ubiquitin ligase TRIM65 promotes colorectal cancer metastasis by targeting ARHGAP35 for protein degradation. Oncogene 55 31332286
2021 The E3 Ubiquitin Ligase TRIM65 Negatively Regulates Inflammasome Activation Through Promoting Ubiquitination of NLRP3. Frontiers in immunology 53 34512673
2020 TRIM65 E3 ligase targets VCAM-1 degradation to limit LPS-induced lung inflammation. Journal of molecular cell biology 47 31310649
2020 Circ_0011292 Enhances Paclitaxel Resistance in Non-Small Cell Lung Cancer by Regulating miR-379-5p/TRIM65 Axis. Cancer biotherapy & radiopharmaceuticals 47 32833503
2019 LncRNA LINC01857 promotes growth, migration, and invasion of glioma by modulating miR-1281/TRIM65 axis. Journal of cellular physiology 44 31049960
2017 ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65. Cell death & disease 44 28594402
2016 TRIM65 negatively regulates p53 through ubiquitination. Biochemical and biophysical research communications 40 27012201
2023 Trim65 attenuates isoproterenol-induced cardiac hypertrophy by promoting autophagy and ameliorating mitochondrial dysfunction via the Jak1/Stat1 signaling pathway. European journal of pharmacology 28 37080331
2023 Berberine attenuates depression-like behavior by modulating the hippocampal NLRP3 ubiquitination signaling pathway through Trim65. International immunopharmacology 26 37595491
2016 Knockdown of TRIM65 inhibits lung cancer cell proliferation, migration and invasion: A therapeutic target in human lung cancer. Oncotarget 25 27829229
2024 TRIM65 promotes renal cell carcinoma through ubiquitination and degradation of BTG3. Cell death & disease 23 38777825
2022 TRIM65 Promotes Cervical Cancer Through Selectively Degrading p53-Mediated Inhibition of Autophagy and Apoptosis. Frontiers in oncology 23 35402260
2024 TRIM65/NF2/YAP1 Signaling Coordinately Orchestrates Metabolic and Immune Advantages in Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 39005234
2022 TRIM65 determines the fate of a novel subtype of pituitary neuroendocrine tumors via ubiquitination and degradation of TPIT. Neuro-oncology 21 35218667
2024 TRIM65 knockout inhibits the development of HCC by polarization tumor-associated macrophages towards M1 phenotype via JAK1/STAT1 signaling pathway. International immunopharmacology 20 38218012
2026 Long Noncoding RNA MALAT1 Knockdown Inhibits Proliferation, Migration, and Invasion and Promotes Apoptosis in Non-Small-Cell Lung Cancer Cells Through Regulating miR-515-3p/TRIM65 Axis. Cancer biotherapy & radiopharmaceuticals 18 33395541
2024 TRIM65 deficiency alleviates renal fibrosis through NUDT21-mediated alternative polyadenylation. Cell death and differentiation 17 38951701
2021 TRIM65 Promotes Invasion of Endometrial Stromal Cells by Activating ERK1/2/C-myc Signaling via Ubiquitination of DUSP6. The Journal of clinical endocrinology and metabolism 17 33146694
2024 E3 ligase TRIM65 alleviates intestinal ischemia/reperfusion injury through inhibition of TOX4-mediated apoptosis. Cell death & disease 15 38212319
2023 TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis. Atherosclerosis 15 38301602
2022 Knockdown of TRIM65 suppressed the proliferation and invasiveness of gastric cancer cells by restricting the ubiquitin degradation of PPM1A. Experimental cell research 14 35421368
2018 TRIM65 is a potential oncogenic protein via ERK1/2 on Jurkat and Raji cells: A therapeutic target in human lymphoma malignancies. Cell biology international 14 30039885
2021 LncRNA LINC00963 promotes colorectal cancer cell proliferation and metastasis by regulating miR‑1281 and TRIM65. Molecular medicine reports 13 34498706
2014 Trim65: a cofactor for regulation of the microRNA pathway. RNA biology 13 25483047
2023 LPS inhibits TRIM65 expression in macrophages and C57BL/6J mouse by activating the ERK1/2 signaling pathway. Experimental and therapeutic medicine 12 37021067
2022 TRIM65 Promotes Malignant Cell Behaviors in Triple-Negative Breast Cancer by Impairing the Stability of LATS1 Protein. Oxidative medicine and cellular longevity 12 36035221
2025 TRIM65 as a key regulator of ferroptosis and glycolysis in lactate-driven renal tubular injury and diabetic kidney disease. Cell reports 10 40748757
2021 TRIM65 in White Matter Lesions, Innate Immunity, and Tumor. Current molecular pharmacology 10 33538683
2024 Intestinal metabolite UroB alleviates cerebral ischemia/reperfusion injury by promoting competition between TRIM65 and TXNIP for binding to NLRP3 inflammasome in response to neuroinflammation. Biochimica et biophysica acta. Molecular basis of disease 9 38360072
2024 TRIM65 Suppresses oxLDL-induced Endothelial Inflammation by Interaction with VCAM-1 in Atherogenesis. Current medicinal chemistry 8 37608612
2019 The Associations of PMF1, ICAM1, AGT, TRIM65, FBF1, and ACOX1 Variants With Leukoaraiosis in Chinese Population. Frontiers in genetics 7 31396257
2018 Combinatory inhibition of TRIM65 and MDM2 in lung cancer cells. Biochemical and biophysical research communications 7 30454706
2024 TRIM65 regulates innate immune signaling by enhancing K6-linked ubiquitination of IRF3 and its chromatin recruitment. Cell reports 5 39580801
2025 Trim65 mitigates doxorubicin-induced myocardial injury by reducing ferroptosis. Experimental cell research 4 40447212
2025 Research and development prospects of TRIM65. Journal of cancer research and clinical oncology 3 40844633
2024 Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription. Viruses 3 38932182
2025 The Magic and Mystery of TRIM65 in Diseases. Current medicinal chemistry 2 38939997
2025 TRIM65 regulates glucose metabolic reprogramming to promote glioma cell proliferation via ubiquitination and degradation of AMPK. NPJ precision oncology 1 40473847
2025 Sevoflurane Alleviates Myocardial Ischemia/Reperfusion Injury Via Regulating TRIM65-Mediated Ubiquitination Modification of ALOX5. Applied biochemistry and biotechnology 1 41182544
2026 Involvement of c-Myc/WWP1/TRIM65 Axis in Renal Fibrosis. Biomolecules 0 41897310
2025 Knockdown of TRIM65 Inhibits Neoangiogenesis in Proliferative Diabetic Retinopathy by Regulating miR29a-3p. Current medicinal chemistry 0 40539336

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