Affinage

TRIM59

Tripartite motif-containing protein 59 · UniProt Q8IWR1

Length
403 aa
Mass
47.1 kDa
Annotated
2026-06-10
100 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM59 is a RING-domain E3 ubiquitin ligase that controls the abundance and signaling output of a broad set of substrates and thereby sits at the intersection of ubiquitin-proteasome regulation, innate immune signaling, autophagy, ferroptosis, and cell-cycle control (PMID:25046164, PMID:30231667, PMID:31488827). Its canonical activity is K48-linked polyubiquitination driving proteasomal degradation, demonstrated for tumor suppressors and signaling regulators including p53 (PMID:25046164), TRAF6 (PMID:30231667), PTEN (PMID:32165307), PPM1A and PPM1B (PMID:31875525, PMID:32348176), ACAT1 (PMID:40790033), ANXA2 (PMID:41971643), and NLRP3 (PMID:38291200); catalytic activity depends on an intact RING domain, as a C30A active-site mutant abolishes substrate degradation and its downstream effects (PMID:41971643). Rather than acting purely as a degrader, TRIM59 also functions as a stabilizing scaffold: it shields STAT3 from phosphatase-mediated dephosphorylation (by TC45/TCPTP) to sustain transcriptional activity (PMID:29386185, PMID:36523164), and it protects PDCD10 and RBPJ from K63-linked-ubiquitin-driven autophagic turnover (PMID:30408026, PMID:30653426, PMID:39725730). A regulatory module governs its compartmental activity—CDK5-mediated phosphorylation at S308 recruits PIN1 for cis-trans isomerization and importin α5-dependent nuclear import, where nuclear TRIM59 degrades the histone variant macroH2A1 to enhance STAT3 signaling (PMID:31488827). Through these activities TRIM59 modulates NF-κB and IRF3/7 innate immune signaling (PMID:22588174), autophagy via the TRAF6–BECN1 axis (PMID:30231667), ferroptosis through GPX4, TMEM164 and ANXA2 (PMID:36417114, PMID:41971643, PMID:40795049), and macrophage polarization and inflammasome function (PMID:38992114, PMID:32133014, PMID:38291200). Its expression is transcriptionally driven by NF-κB/p65 and repressed by the androgen receptor and an Sp1/Nrf1–JNK axis (PMID:30932261, PMID:36544044, PMID:31883458), and Trim59 is essential for development, with knockout embryos failing gastrulation by E9.5 due to defective WASH-dependent F-actin assembly (PMID:29467473).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2011 Low

    Established TRIM59 as an oncogenic RING-finger protein, framing it as a candidate post-translational regulator before any substrate was known.

    Evidence shRNA knockdown with cell-cycle analysis and prostate-specific transgenic mouse model

    PMID:21593385

    Open questions at the time
    • Phospho-forms identified by ELISA without kinase assignment
    • Ras pathway link is correlative from microarray
    • no substrate or direct enzymatic activity demonstrated
  2. 2012 Medium

    First placed TRIM59 in a defined signaling pathway by showing it negatively regulates TLR-driven NF-κB and IRF3/7 innate immune signaling via ECSIT.

    Evidence Co-IP, luciferase reporters, and IRF3/7 phosphorylation immunoblotting with siRNA knockdown

    PMID:22588174

    Open questions at the time
    • Whether regulation is ubiquitin-dependent not resolved
    • single lab
    • no in vivo confirmation
  3. 2014 High

    Identified the first direct substrate, defining TRIM59 as an E3 ligase that degrades p53 to suppress tumor-suppressor output.

    Evidence Reciprocal Co-IP, ubiquitination assay, and KD/OE in gastric cancer cells

    PMID:25046164

    Open questions at the time
    • Ubiquitin linkage type not specified
    • ubiquitination site on p53 not mapped
  4. 2018 High

    Revealed TRIM59 acts as both degrader and protector, controlling autophagy through TRAF6 degradation and BECN1 transcription, and stabilizing PDCD10 and STAT3.

    Evidence Linkage-specific (K48/K63) ubiquitination assays, selective-autophagy flux readouts, phosphatase-protection Co-IP, and rescue experiments

    PMID:29386185 PMID:30231667 PMID:30408026 PMID:30653426

    Open questions at the time
    • Mechanism by which TRIM59 distinguishes degradative vs protective substrates unknown
    • how scaffold function relates to RING activity unclear
  5. 2019 High

    Defined the regulatory switch controlling TRIM59 nuclear function: CDK5-S308 phosphorylation, PIN1 isomerization and importin α5 import enable nuclear macroH2A1 degradation.

    Evidence In vitro kinase assay, S308 mutagenesis, PIN1-binding assay, subcellular fractionation, ubiquitination assay, and intracranial xenograft

    PMID:31488827

    Open questions at the time
    • Whether this module governs other nuclear substrates not tested
    • structural basis of importin recognition unresolved
  6. 2019 Medium

    Expanded the substrate set toward cell-cycle and viral-defense roles, including PPM1B degradation and direct RING-domain binding to PRRSV nsp11.

    Evidence Co-IP, mass spectrometry, ubiquitination assays, domain-mapping deletion constructs, and antiviral assays

    PMID:31683196 PMID:31875525

    Open questions at the time
    • Single-lab findings
    • ubiquitination sites not mapped
  7. 2020 Medium

    Demonstrated cell-type-specific and intercellular functions: exosomal transfer to macrophages, ABHD5/PTEN/STAT1/PPM1A degradation, and PIAS1-recruited STAT1 suppression.

    Evidence Co-IP, ubiquitination assays, PLA, exosome transfer, macrophage conditional KO mice, and tumor/inflammation models

    PMID:32165307 PMID:32348176 PMID:32867817 PMID:33045573 PMID:38992114

    Open questions at the time
    • Substrate-selectivity determinants across cell types unknown
    • individual studies single-lab
  8. 2018 Medium

    Established TRIM59 as developmentally essential, linking it to cytoskeletal regulation via K63-ubiquitination of WASH and F-actin assembly.

    Evidence Conditional Trim59 KO with embryonic-lethal phenotyping, Co-IP, and K63-specific ubiquitination assay

    PMID:29467473

    Open questions at the time
    • Mechanism linking WASH ubiquitination to actin polymerization not fully resolved
    • single lab
  9. 2022 Medium

    Connected TRIM59 to ferroptosis and to viral STAT3 hyperactivation, broadening its disease relevance to NAFLD and COVID-19 kidney injury.

    Evidence Co-IP, ubiquitination assays, ferroptosis rescue, and in vivo/autopsy validation

    PMID:36417114 PMID:36523164

    Open questions at the time
    • GPX4 ubiquitination site not mapped
    • TCPTP-dissociation mechanism not structurally defined
  10. 2024 Medium

    Consolidated TRIM59 as a multi-pathway regulator with mapped ubiquitin chemistry: RING-dependent (C30A) ANXA2/K48 degradation, K27/K63 ACAT1 at K174, NLRP3 degradation, RBPJ stabilization, IRF6 and AXIN1 degradation, and PIN1/importin-driven SFPQ-dependent splicing.

    Evidence Active-site (C30A) and site-specific (K174) mutagenesis, linkage-specific ubiquitination, CHX chase, ChIP/reporter, splicing analysis, and in vivo AAV/xenograft models

    PMID:38291200 PMID:39263074 PMID:39725730 PMID:40790033 PMID:40796729 PMID:41413601 PMID:41971643

    Open questions at the time
    • Unified rules governing substrate choice and chain-type selection unknown
    • many substrate sites still unmapped
    • several studies single-lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single E3 ligase selects between degradative and stabilizing outcomes and among diverse substrates across tissues remains unresolved.
  • No structural model of substrate recognition
  • no systematic mapping of which substrates depend on the CDK5/PIN1/importin nuclear module
  • determinants of K48 vs K63 vs K27 chain choice undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 5 GO:0098772 molecular function regulator activity 4 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-9612973 Autophagy 3
Partners
NLRP3P53PDCD10PTENRBPJSTAT1STAT3TRAF6

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 TRIM59 physically interacts with p53 and promotes its ubiquitination and proteasome-dependent degradation, reducing p53 protein levels and suppressing p53 target gene expression in gastric cancer cells. Co-immunoprecipitation, ubiquitination assay, immunoblotting, knockdown/overexpression in gastric cancer cell lines Gastroenterology High 25046164
2012 TRIM59 interacts with ECSIT (an adaptor required for TLR-mediated signaling) and negatively regulates NF-κB and IRF-3/7-mediated innate immune signaling; overexpression represses NF-κB, IFN-β promoter, and ISRE transcriptional activities and inhibits IRF3/IRF7 phosphorylation and dimerization. Co-immunoprecipitation, luciferase reporter assays, immunoblotting of IRF3/IRF7 phosphorylation, siRNA knockdown Biochemical and biophysical research communications Medium 22588174
2018 TRIM59 regulates autophagy through two mechanisms: (1) it negatively modulates NF-κB signaling to suppress BECN1 transcription, and (2) it mediates K48-linked ubiquitination of TRAF6 to promote TRAF6 proteasomal degradation, thereby reducing TRAF6-induced K63-linked ubiquitination of BECN1 and inhibiting formation of the BECN1-PIK3C3 complex. Co-immunoprecipitation, ubiquitination assays (K48/K63-specific), luciferase reporter for NF-κB, immunoblotting, KD/OE in NSCLC cells Autophagy High 30231667
2018 TRIM59 stabilizes PDCD10 by suppressing RNFT1-induced K63 polyubiquitination of PDCD10, thereby blocking p62/SQSTM1-selective autophagic degradation of PDCD10; stable PDCD10 suppresses RhoA-ROCK1 signaling to promote mesenchymal invasiveness. Co-immunoprecipitation, ubiquitination assays (K63-specific), autophagy flux assays, TRIM59/PDCD10 KD/OE, rescue with ROCK inhibitor or PDCD10 overexpression PLoS biology High 30408026 30653426
2019 CDK5 (activated by EGFR signaling) directly phosphorylates TRIM59 at serine 308; this recruits PIN1 for cis-trans isomerization of TRIM59, which enables TRIM59 binding to importin α5 and nuclear translocation. Nuclear TRIM59 then ubiquitinates and degrades the histone variant macroH2A1, leading to enhanced STAT3 signaling and GBM tumorigenicity. In vitro kinase assay (CDK5-TRIM59), Co-IP, mutagenesis (S308 mutant), PIN1 binding assay, subcellular fractionation/nuclear localization, ubiquitination assay for macroH2A1, intracranial xenograft model Nature communications High 31488827
2018 TRIM59 interacts with nuclear STAT3 and prevents its dephosphorylation by the nuclear phosphatase TC45, thereby maintaining STAT3 transcriptional activation and promoting GBM tumorigenesis downstream of EGFR/SOX9 signaling. Co-immunoprecipitation, STAT3 phosphorylation immunoblotting, TRIM59 KD with rescue, orthotopic xenograft, correlation in GBM patient samples Cancer research High 29386185
2020 Cancer cell-derived exosomal TRIM59 is transferred to macrophages; in macrophages TRIM59 physically interacts with ABHD5 and promotes its K48-linked ubiquitination and proteasomal degradation, causing metabolic reprogramming and NLRP3 inflammasome activation with IL-1β secretion that promotes lung cancer progression. Co-immunoprecipitation, ubiquitination assay, proximity ligation assay, immunofluorescence, exosome transfer experiments, in vivo LLC mouse models, rescue experiments Journal of experimental & clinical cancer research High 32867817
2019 TRIM59 interacts with PPM1B (a phosphatase that dephosphorylates CDKs) and promotes PPM1B degradation via ubiquitination, leading to increased CDK phosphorylation and cell cycle progression in hepatocellular carcinoma. Co-immunoprecipitation, mass spectrometry, immunofluorescence, ubiquitination assay, immunoblotting of CDKs, KD/OE in HCC cells and xenograft model Cancer letters Medium 31875525
2020 TRIM59 interacts with PTEN and promotes its ubiquitination, leading to PTEN degradation and consequent activation of AKT and upregulation of HK2, increasing glycolysis and contributing to cisplatin resistance in NSCLC cells. Co-immunoprecipitation, ubiquitination assay, immunoblotting of PTEN/p-AKT/HK2, KD/OE in cisplatin-resistant A549/DDP cells, xenograft model Gene Medium 32165307
2020 TRIM59 inhibits STAT1 signaling in macrophages by ubiquitinating and degrading STAT1, thereby suppressing M1 macrophage polarization and inhibiting colorectal cancer progression. Co-immunoprecipitation, ubiquitination assay, macrophage-specific conditional knockout mice, CRC mouse models, immunoblotting Scientific reports Medium 38992114
2020 TRIM59 translocates from cytoplasm to nucleus in LPS-stimulated macrophages and directly binds STAT1, recruiting PIAS1 to STAT1 to suppress JAK2-STAT1 pathway activation, thereby inhibiting iNOS expression and NO production. Nuclear/cytoplasmic fractionation, Co-immunoprecipitation, immunofluorescence, iNOS/NO measurement, KD/OE in macrophages International immunopharmacology Medium 33045573
2022 TRIM59 interacts with GPX4 and promotes its ubiquitination and proteasomal degradation, thereby promoting ferroptosis and steatosis in NAFLD models. Co-immunoprecipitation, ubiquitination assay, ferroptosis inhibitor rescue (deferoxamine), GPX4 overexpression rescue, KD/OE in NAFLD cell/mouse models Human cell Medium 36417114
2020 TRIM59 inhibits PPM1A through K48-linked ubiquitination and proteasomal degradation (without affecting PPM1A mRNA), activating TGF-β/Smad2/3 signaling and promoting invasion of ectopic endometrial stromal cells in endometriosis. Co-immunoprecipitation, ubiquitination assay, RT-PCR/Western blot showing post-translational effect, Transwell invasion assay, KD/OE in endometrial stromal cells American journal of physiology. Cell physiology Medium 32348176
2022 SARS-CoV-2 viral protein ORF3A elevates TRIM59 protein levels; TRIM59 interacts with both ORF3A and STAT3, and excessive TRIM59 dissociates the phosphatase TCPTP from STAT3, preventing STAT3 dephosphorylation and causing persistent STAT3 activation and renal tubular cell injury. Co-immunoprecipitation, immunoblotting, TRIM59 KD/OE in renal tubular cell line, zebrafish and mouse in vivo models, kidney autopsy analysis from COVID-19 patients Molecular therapy Medium 36523164
2018 TRIM59 deficiency in embryos disrupts F-actin polymerization during inner cell mass differentiation; TRIM59 mediates K63-linked ubiquitination of WASH, and this ubiquitination is required for proper F-actin assembly. Trim59-null embryos are embryonic lethal by E9.5 due to failure of gastrulation. Conditional knockout mouse (Trim59-/-), Co-IP with actin/myosin-associated proteins, ubiquitination assay (K63-specific) for WASH, immunofluorescence of F-actin, embryo phenotyping Cell death & disease Medium 29467473
2019 TRIM59 interacts with NLRP3 inflammasome components in macrophages and promotes phagocytosis activity; macrophage-specific TRIM59 conditional knockout mice show increased susceptibility to CLP sepsis with higher bacterial burden and cytokine dysregulation, indicating TRIM59 is required for macrophage inflammatory and phagocytic functions. Macrophage-specific conditional knockout (Trim59Lyz-Cre) mice, CLP sepsis model, cytokine measurement, phagocytosis assay, NF-κB pathway analysis Frontiers in immunology Medium 32133014
2024 TRIM59 directly interacts with RBPJ and stabilizes it through K63-linked ubiquitination; RBPJ in turn transcriptionally upregulates TRIM59 expression, forming a positive feedback loop that activates Notch signaling and drives gemcitabine resistance in pancreatic cancer. Co-immunoprecipitation, K63-specific ubiquitination assay, luciferase reporter for Notch/RBPJ transcriptional activity, ChIP, KD/OE in pancreatic cancer cells and xenograft models Cell death & disease Medium 39725730
2022 TRIM59 is phosphorylated downstream of circWhsc1 (delivered via endothelial extracellular vesicles), and phosphorylated TRIM59 has enhanced binding to STAT3, leading to STAT3 phosphorylation, Cyclin B2 induction, and cardiomyocyte proliferation. Western blot of TRIM59 phosphorylation, Co-IP (TRIM59-STAT3), RNA pulldown, KD/OE in cardiomyocytes, in vivo cardiac injury models Journal of advanced research Low 36587763
2019 TRIM59 interacts with PRRSV nonstructural protein nsp11 through the N-terminal RING domain of TRIM59 and the C-terminal NendoU domain of nsp11; TRIM59 overexpression inhibits PRRSV replication while TRIM59 siRNA knockdown enhances viral production. Co-immunoprecipitation in HEK293T cells and PRRSV-infected PAMs, domain mapping by deletion constructs, KD/OE antiviral assays Research in veterinary science Medium 31683196
2024 TRIM59 directly ubiquitinates NLRP3 and promotes its proteasomal degradation in microglia, thereby reducing pyroptosis and alleviating cerebral ischemia/reperfusion injury. Co-immunoprecipitation, ubiquitination assay for NLRP3, flow cytometry for pyroptosis, OGD/R cell model, MCAO rat model, KD/OE of TRIM59 Scientific reports Medium 38291200
2023 SLC35F2 competitively interacts with the E3 ubiquitin ligase SYVN1 of TRIM59, thereby stabilizing TRIM59 expression; stable TRIM59 promotes ubiquitination and degradation of p53, inhibiting ferroptosis in pancreatic cancer cells. Co-immunoprecipitation (SLC35F2-SYVN1-TRIM59), ubiquitination assay for p53, KD/OE experiments, PDX in vivo models Oncogene Medium 37740007
2022 TRIM59 interacts with STAT3 in gefitinib-resistant EGFR-mutant lung adenocarcinoma cells; TRIM59 deficiency impairs STAT3 activation, and STAT3-specific knockdown resensitizes TRIM59-proficient cells to gefitinib. Co-immunoprecipitation, STAT3 phosphorylation immunoblotting, shRNA knockdown epistasis, cell viability/apoptosis assays Life sciences Low 30902544
2022 AR (androgen receptor) binds the TRIM59 promoter and represses its transcription; ARPI treatment reverses AR-mediated repressive epigenetic modifications on the TRIM59 gene. Upregulated TRIM59 promotes neuroendocrine differentiation by enhancing degradation of RB1 and p53 and upregulating SOX2. ChIP (AR binding to TRIM59 promoter), epigenetic modification analysis, ubiquitination/degradation assays for RB1 and p53, KD/OE in prostate cancer cells Oncogene Medium 36544044
2024 TRIM59 directly interacts with IRF6 and promotes its polyubiquitination and degradation; IRF6 loss derepresses PGM1 transcription, enhancing glycolysis in neuroblastoma cells. Co-immunoprecipitation, ubiquitination assay, RNA-seq, ChIP and dual-luciferase reporter assay for IRF6-PGM1 axis, KD/OE in neuroblastoma cells and xenograft models Cell death & disease Medium 40796729
2024 TRIM59 promotes K27- and K63-linked ubiquitination and degradation of ACAT1 at lysine 174, disrupting mitochondrial cardiolipin metabolism and inhibiting mitochondria-dependent apoptosis in papillary renal cell carcinoma. Co-immunoprecipitation, linkage-specific ubiquitination assays (K27/K63), site-specific mutagenesis (K174), mitochondrial apoptosis assays, KD/OE in pRCC cells and xenograft Cell death & disease Medium 40790033
2024 TRIM59 mediates K48-linked polyubiquitination of ANXA2 leading to proteasomal degradation; this protects neurons from ferroptosis and promotes functional recovery after spinal cord injury. A catalytically inactive C30A RING-domain mutant of TRIM59 abolishes the neuroprotective effect. Co-immunoprecipitation, K48-specific ubiquitination assay, CHX chase experiment, C30A RING-domain mutagenesis, BODIPY C11/ROS ferroptosis assays, AAV9 in vivo SCI model Journal of orthopaedic translation Medium 41971643
2024 TRIM59 promotes ubiquitination and degradation of TMEM164, thereby suppressing autophagy-dependent ferroptosis in NSCLC cells; TRIM59 knockdown inhibits TMEM164 ubiquitination and induces ferroptosis. Co-immunoprecipitation, ubiquitination assay, ferroptosis markers (Fe2+, MDA, GSH), autophagy markers, KD/OE in A549 cells Bioscience, biotechnology, and biochemistry Low 40795049
2024 TRIM59 deletion in neuroblastoma promotes nuclear translocation of the splicing factor SFPQ via the PIN1-importin α axis and PRMT1-dependent asymmetric dimethylation of SFPQ; nuclear SFPQ shifts SEMA4F splicing from the SEMA4F-L to SEMA4F-S isoform, promoting neuronal differentiation. RNA-seq with rMATS splicing analysis, mass spectrometry, Co-IP (TRIM59-SFPQ), nuclear fractionation, isoform-specific rescue experiments, AAV-delivered TRIM59-gRNA in vivo Journal of experimental & clinical cancer research Medium 41413601
2024 TRIM59 is required for spermatogonial cell maintenance; it ubiquitinates AXIN1 to promote its degradation and thereby activates β-catenin signaling in GC-1 spermatogonial cells. Co-immunoprecipitation, ubiquitination assay for AXIN1, β-catenin pathway immunoblotting, KD/OE in GC-1 cells, rescue by β-catenin agonist Heliyon Low 39263074
2019 BCG-induced upregulation of TRIM59 on macrophage membranes is mediated through the TLR2/TLR4 → IRF5 signaling pathway; blocking TLR2/4 or siRNA knockdown of IRF5 prevents BCG-induced TRIM59 expression. TRIM59 is identified as a membrane-localized protein on BCG-activated macrophages. TLR2/4-neutralizing antibodies, IRF5 siRNA knockdown, immunostaining for membrane localization, Western blot for TRIM59/IRF5/TNF-α Protein and peptide letters Low 28820065
2019 NF-κB (p65) directly binds to the TRIM59 promoter and transcriptionally activates TRIM59 expression in NSCLC; eugenol suppresses p65 expression to downregulate TRIM59. Chromatin immunoprecipitation (ChIP) for p65 binding TRIM59 promoter, luciferase reporter assay, xenograft tumor model Phytotherapy research Medium 30932261
2019 Sp1 and Nrf1 transcription factors directly bind to the proximal TRIM59 promoter to regulate its transcription in macrophages; LPS decreases Sp1 nuclear translocation/binding while increasing Nrf1 nuclear translocation/binding, reducing TRIM59 expression via a JNK-dependent mechanism. Chromatin immunoprecipitation (ChIP), TRIM59 promoter luciferase reporter assay, nuclear fractionation, JNK inhibitor treatment, KD/OE in macrophages Cellular signalling Medium 31883458
2011 TRIM59 is an oncogenic RING-finger (TRIM family) protein expressed as two phosphorylated forms (p53 and p55) with Ser/Thr and Tyr phosphorylation, respectively; shRNA knockdown of TRIM59 in prostate cancer cells causes S-phase arrest, and TRIM59 transgenic overexpression in the prostate drives tumorigenesis correlated with Ras pathway gene upregulation. ELISA quantification of phospho-TRIM59 forms, shRNA knockdown with cell cycle analysis, differential cDNA microarray, prostate-specific TRIM59 transgenic mouse model Molecular cancer therapeutics Low 21593385

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 DNA methylation of the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59 genes for age prediction from blood, saliva, and buccal swab samples. Forensic science international. Genetics 147 30300865
2014 TRIM59 is up-regulated in gastric tumors, promoting ubiquitination and degradation of p53. Gastroenterology 147 25046164
2020 Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression. Journal of experimental & clinical cancer research : CR 130 32867817
2015 TRIM59 Promotes the Proliferation and Migration of Non-Small Cell Lung Cancer Cells by Upregulating Cell Cycle Related Proteins. PloS one 116 26599082
2018 TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1. Autophagy 93 30231667
2012 TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways. Biochemical and biophysical research communications 82 22588174
2018 TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10. PLoS biology 77 30408026
2001 Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026p (Mrf1'p), 2-enoyl thioester reductases essential for mitochondrial respiratory competence. Molecular and cellular biology 75 11509667
1998 Upregulation of a new microglial gene, mrf-1, in response to programmed neuronal cell death and degeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 9698327
2003 Characterization of 2-enoyl thioester reductase from mammals. An ortholog of YBR026p/MRF1'p of the yeast mitochondrial fatty acid synthesis type II. The Journal of biological chemistry 66 12654921
2017 TRIM59 facilitates the proliferation of colorectal cancer and promotes metastasis via the PI3K/AKT pathway. Oncology reports 58 28534983
2019 CDK5-dependent phosphorylation and nuclear translocation of TRIM59 promotes macroH2A1 ubiquitination and tumorigenicity. Nature communications 57 31488827
1992 The yeast nuclear gene MRF1 encodes a mitochondrial peptide chain release factor and cures several mitochondrial RNA splicing defects. Nucleic acids research 52 1475194
2018 TRIM59 Promotes Gliomagenesis by Inhibiting TC45 Dephosphorylation of STAT3. Cancer research 50 29386185
2022 TRIM59 promotes steatosis and ferroptosis in non-alcoholic fatty liver disease via enhancing GPX4 ubiquitination. Human cell 47 36417114
2022 METTL3-Mediated N6-Methyladenosine Modification of Trim59 mRNA Protects Against Sepsis-Induced Acute Respiratory Distress Syndrome. Frontiers in immunology 45 35693774
2012 TRIM59, a novel multiple cancer biomarker for immunohistochemical detection of tumorigenesis. BMJ open 44 23048060
2017 Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via TGF-β/Smad2/3 signaling pathway in bladder cancer cells. OncoTargets and therapy 42 28331343
2016 TRIM59 is upregulated and promotes cell proliferation and migration in human osteosarcoma. Molecular medicine reports 42 27121462
2011 Characterization of the oncogenic activity of the novel TRIM59 gene in mouse cancer models. Molecular cancer therapeutics 41 21593385
2022 Extracellular vesicle-derived CircWhsc1 promotes cardiomyocyte proliferation and heart repair by activating TRIM59/STAT3/Cyclin B2 pathway. Journal of advanced research 38 36587763
2019 TRIM59 knockdown inhibits cell proliferation by down-regulating the Wnt/β-catenin signaling pathway in neuroblastoma. Bioscience reports 38 30389710
2016 Knockdown of Tripartite-59 (TRIM59) Inhibits Cellular Proliferation and Migration in Human Cervical Cancer Cells. Oncology research 38 27662486
2019 Knockdown of tripartite motif 59 (TRIM59) inhibits proliferation in cholangiocarcinoma via the PI3K/AKT/mTOR signalling pathway. Gene 36 30822475
2019 TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages through JNK signaling pathway. Cellular signalling 36 31883458
2020 TRIM59 knockdown blocks cisplatin resistance in A549/DDP cells through regulating PTEN/AKT/HK2. Gene 35 32165307
2019 Phloem Companion Cell-Specific Transcriptomic and Epigenomic Analyses Identify MRF1, a Regulator of Flowering. The Plant cell 34 30670485
2019 TRIM59 promotes tumor growth in hepatocellular carcinoma and regulates the cell cycle by degradation of protein phosphatase 1B. Cancer letters 34 31875525
2020 TRIM59 Protects Mice From Sepsis by Regulating Inflammation and Phagocytosis in Macrophages. Frontiers in immunology 31 32133014
2018 Hypermethylation of TRIM59 and KLF14 Influences Cell Death Signaling in Familial Alzheimer's Disease. Oxidative medicine and cellular longevity 30 29849909
2019 TRIM59 loss in M2 macrophages promotes melanoma migration and invasion by upregulating MMP-9 and Madcam1. Aging 29 31600735
2019 TRIM59 deficiency curtails breast cancer metastasis through SQSTM1-selective autophagic degradation of PDCD10. Autophagy 28 30653426
2019 Eugenol inhibits non-small cell lung cancer by repressing expression of NF-κB-regulated TRIM59. Phytotherapy research : PTR 27 30932261
2022 TRIM59 is suppressed by androgen receptor and acts to promote lineage plasticity and treatment-induced neuroendocrine differentiation in prostate cancer. Oncogene 25 36544044
2016 Knockdown of tripartite motif 59 (TRIM59) inhibits tumor growth in prostate cancer. European review for medical and pharmacological sciences 25 27981550
2023 SLC35F2-SYVN1-TRIM59 axis critically regulates ferroptosis of pancreatic cancer cells by inhibiting endogenous p53. Oncogene 23 37740007
2020 TRIM59 attenuates IL-1β-driven cartilage matrix degradation in osteoarthritis via direct suppression of NF-κB and JAK2/STAT3 signaling pathway. Biochemical and biophysical research communications 22 32560815
2018 TRIM59 induces epithelial-to-mesenchymal transition and promotes migration and invasion by PI3K/AKT signaling pathway in medulloblastoma. Oncology letters 22 29805559
2018 An TRIM59-CDK6 axis regulates growth and metastasis of lung cancer. Journal of cellular and molecular medicine 22 30515965
2022 SARS-CoV-2 viral protein ORF3A injures renal tubules by interacting with TRIM59 to induce STAT3 activation. Molecular therapy : the journal of the American Society of Gene Therapy 21 36523164
2020 TRIM59 inhibits PPM1A through ubiquitination and activates TGF-β/Smad signaling to promote the invasion of ectopic endometrial stromal cells in endometriosis. American journal of physiology. Cell physiology 21 32348176
2012 A novel accessory molecule Trim59 involved in cytotoxicity of BCG-activated macrophages. Molecules and cells 21 22949172
2024 IGF2BP2-m6A-circMMP9 axis recruits ETS1 to promote TRIM59 transcription in laryngeal squamous cell carcinoma. Scientific reports 18 38321126
2020 TRIM59 suppresses NO production by promoting the binding of PIAS1 and STAT1 in macrophages. International immunopharmacology 18 33045573
2019 TRIM59 promotes gefitinib resistance in EGFR mutant lung adenocarcinoma cells. Life sciences 18 30902544
2019 Tripartite Motif-Containing Protein 59 (TRIM59) Promotes Epithelial Ovarian Cancer Progression via the Focal Adhesion Kinase(FAK)/AKT/Matrix Metalloproteinase (MMP) Pathway. Medical science monitor : international medical journal of experimental and clinical research 17 31062766
2018 Embryonic lethality in mice lacking Trim59 due to impaired gastrulation development. Cell death & disease 17 29467473
2024 TRIM59 deficiency promotes M1 macrophage activation and inhibits colorectal cancer through the STAT1 signaling pathway. Scientific reports 16 38992114
2020 TRIM59, amplified in ovarian cancer, promotes tumorigenesis through the MKP3/ERK pathway. Journal of cellular physiology 16 31951023
2004 Mutations in the yeast mrf1 gene encoding mitochondrial release factor inhibit translation on mitochondrial ribosomes. The Journal of biological chemistry 16 14734569
2002 ATP selectively suppresses the synthesis of the inflammatory protein microglial response factor (MRF)-1 through Ca(2+) influx via P2X(7) receptors in cultured microglia. Brain research 16 12363408
2018 Knockdown of MAML1 inhibits proliferation and induces apoptosis of T-cell acute lymphoblastic leukemia cells through SP1-dependent inactivation of TRIM59. Journal of cellular physiology 15 30370525
2017 TRIM59 promotes cell proliferation, migration and invasion in human hepatocellular carcinoma cells. Die Pharmazie 15 29442042
1993 Single point mutations in domain II of the yeast mitochondrial release factor mRF-1 affect ribosome binding. Nucleic acids research 15 8265342
2019 TRIM59 inhibits porcine reproductive and respiratory syndrome virus (PRRSV)-2 replication in vitro. Research in veterinary science 14 31683196
2002 Molecular cloning, mapping and characterization of a novel mouse RING finger gene, Mrf1. Gene 14 12095697
2024 TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation. Heliyon 13 38434050
2020 TRIM59 Promotes Retinoblastoma Progression by Activating the p38-MAPK Signaling Pathway. Investigative ophthalmology & visual science 12 32744597
2024 TRIM59 suppresses the brain ischaemia/reperfusion injury and pyroptosis of microglial through mediating the ubiquitination of NLRP3. Scientific reports 11 38291200
2017 TRIM59 is a key regulator of growth and migration inrenal cell carcinoma. Cellular and molecular biology (Noisy-le-Grand, France) 11 28719348
2002 Selective inflammatory stimulations enhance release of microglial response factor (MRF)-1 from cultured microglia. Glia 11 12420315
2020 Blockade of TRIM59 enhances esophageal cancer cell chemosensitivity to cisplatin by upregulating p53. Oncology letters 10 33240412
2017 BCG Increased Membrane Expression of TRIM59 Through the TLR2/ TLR4/IRF5 Pathway in RAW264.7 Macrophages. Protein and peptide letters 10 28820065
2022 TRIM59 guards ER proteostasis and prevents Bortezomib-mediated colorectal cancer (CRC) cells' killing. Investigational new drugs 9 36306030
1994 Isolation and characterization of MRF-1, a brain-derived DNA-binding protein with a capacity to regulate expression of myelin basic protein gene. The Journal of biological chemistry 9 7527040
1997 The sequence of a nearly unclonable 22.8 kb segment on the left arm chromosome VII from Saccharomyces cerevisiae reveals ARO2, RPL9A, TIP1, MRF1 genes and six new open reading frames. Yeast (Chichester, England) 8 9046099
1996 The nuclear Kluyveromyces lactis MRF1 gene encodes a mitochondrial class I peptide chain release factor that is important for cell viability. Current genetics 8 8662205
2024 Myeloid Cell Trim59 Deficiency Worsens Experimental Ischemic Stroke and Alters Cerebral Proteomic Profile. Journal of inflammation research 7 39051047
2022 LncRNA BANCR Promotes Endometrial Stromal Cell Proliferation and Invasion in Endometriosis via the miR-15a-5p/TRIM59 Axis. International journal of genomics 7 36262826
2021 TRIM59 promotes osteosarcoma progression via activation of STAT3. Human cell 7 34625908
2019 TRIM59: A membrane protein expressed on Bacillus Calmette-Guérin-activated macrophages that induces apoptosis of fibrosarcoma cells by direct contact. Experimental cell research 7 31479687
2017 Identification of a synonymous variant in TRIM59 gene for gastric cancer risk in a Chinese population. Oncotarget 7 28009992
2022 The role of TRIM59 in immunity and immune-related diseases. International reviews of immunology 6 35975813
2020 miR-4698-Trim59 axis plays a suppressive role in hepatocellular carcinoma. Frontiers in bioscience (Landmark edition) 6 32114426
2020 TRIM59 attenuates inflammation and apoptosis caused by myocardial ischemia reperfusion injury by activating the PI3K/Akt signaling pathway. European review for medical and pharmacological sciences 6 32495925
2024 TRIM59 is required for mouse GC-1 cell maintenance through modulating the ubiquitination of AXIN1. Heliyon 5 39263074
2024 TRIM59/RBPJ positive feedback circuit confers gemcitabine resistance in pancreatic cancer by activating the Notch signaling pathway. Cell death & disease 5 39725730
2023 TRIM59 attenuates ox-LDL-induced endothelial cell inflammation, apoptosis, and monocyte adhesion through AnxA2. Annals of translational medicine 5 36819529
2023 A role of TRIM59 in pulmonary hypertension: modulating the protein ubiquitylation modification. Journal of translational medicine 5 37978515
2025 TRIM59 deficiency aggravates HFD-induced obesity in mice associated with increased adipose tissue inflammation, lipid accumulation, and apoptosis. Cellular signalling 4 40588013
2025 TRIM59 suppresses mitochondrial-associated apoptosis to facilitate progression in papillary renal cell carcinoma via the ACAT1-cardiolipin pathway. Cell death & disease 4 40790033
2024 TRIM25, TRIM28 and TRIM59 and Their Protein Partners in Cancer Signaling Crosstalk: Potential Novel Therapeutic Targets for Cancer. Current issues in molecular biology 4 39451518
2000 Microglial Response Factor (MRF)-1: Constitutive Expression in Ramified Microglia and Upregulation upon Neuronal Death Induced by Ischemia or Glutamate Exposure. Zoological science 4 18517291
2022 Regulations of LINC0196/miR-584-5p/miR-34a-5p/TRIM59 on Progression of Pediatric Neuroblastoma. Cellular and molecular biology (Noisy-le-Grand, France) 3 36227666
2021 [TRIM59 regulates invasion and migration of nasopharyngeal carcinoma cells by targeted modulation of PPM1B]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 3 34308852
2020 TRIM59 attenuates inflammation and apoptosis caused by myocardial ischemia reperfusion injury by activating the PI3K/Akt signaling pathway. European review for medical and pharmacological sciences 3 32329876
2020 Tripartite motif containing 59 (TRIM59) promotes esophageal cancer progression via promoting MST4 expression and ERK pathway. Journal of receptor and signal transduction research 3 32340525
2024 Characterization of tripartite motif containing 59 (TRIM59) in Epinephelus akaara: Insights into its immune involvement and functional properties in viral pathogenesis, macrophage polarization, and apoptosis regulation. Fish & shellfish immunology 2 39645217
2023 Circ_0006324 regulates cell proliferation, cell-cycle progression, apoptosis, and glycolysis of non-small cell lung cancer cells through miR-496/TRIM59 axis. Journal of biochemical and molecular toxicology 2 37545326
2026 PLLP inhibits the progression of WT p53 gastric cancer by reducing p53 protein ubiquitination by binding to TRIM59. The Journal of biological chemistry 1 41791705
2026 TRIM59 alleviates neuronal ferroptosis and promotes functional recovery after spinal cord injury by mediating ubiquitination and degradation of ANXA2. Journal of orthopaedic translation 1 41971643
2025 The σNS protein of NDRV antagonizes TRIM59-mediated antiviral innate immune response of Cherry Valley duck. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 1 39894289
2025 TRIM59 regulates autophagy-dependent ferroptosis in non-small cell lung cancer by modulating the ubiquitination of TMEM164. Bioscience, biotechnology, and biochemistry 1 40795049
2025 Degradation of IRF6 by TRIM59 in tumor cells triggers PGM1-mediated glycolysis to regulate cell proliferation in neuroblastoma. Cell death & disease 1 40796729
2025 Identification of TRIM59 as a Key Biomarker for Ferroptosis Resistance and Immunotherapy Response in Bladder Cancer via Multi-Omics Integration and Machine Learning. Frontiers in bioscience (Landmark edition) 1 41074451
2024 Role of TRIM59 in regulating PPM1A in the pathogenesis of silicosis and the intervention effect of tanshinone IIA. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 1 38908195
2022 [Down-regulation of tripartite motif containing 59 (TRIM59) blocks the NF-κB signaling pathway and inhibits the invasion and migration of nasopharyngeal carcinoma cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 35603650
2025 Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses. Journal of experimental & clinical cancer research : CR 0 41413601
2024 [Effect of TRIM59 Expression Interference on Daunorubicin Chemosensitivity of Chronic Myeloid Leukemia K562 Cells and Its Mechanism]. Zhongguo shi yan xue ye xue za zhi 0 38387898
2015 A single mutation in the 15S rRNA gene confers non sense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria. Microbial cell (Graz, Austria) 0 28357310

Missed literature

Know a paper Affinage missed for TRIM59? Flag it for the maintainers and the community.

No submissions yet.