{"gene":"TRIM29","run_date":"2026-06-10T10:51:56","timeline":{"discoveries":[{"year":2017,"finding":"TRIM29 induces K48-linked ubiquitination of STING (Stimulator of Interferon Genes), leading to its rapid proteasomal degradation, thereby suppressing the cytosolic dsDNA-sensing innate immune pathway and promoting DNA virus persistence.","method":"Mechanistic studies in human airway epithelial cells and Trim29-/- mice; ubiquitination assays; knockdown and knockout functional readouts (IFN production, viral titers)","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal mechanistic validation in multiple cell types and in vivo mouse models, independently replicated in a second paper (PMID:29581886)","pmids":["29038422"],"is_preprint":false},{"year":2018,"finding":"TRIM29 targets STING for K48-linked ubiquitination and proteasomal degradation in macrophages and dendritic cells, negatively regulating the STING-TBK1-IRF3 signaling axis in response to DNA viruses and cytosolic dsDNA.","method":"Ubiquitination assays, TRIM29 KO mice (HSV-1 infection model), IFN measurement, Western blot for STING degradation","journal":"Cell discovery","confidence":"High","confidence_rationale":"Tier 2 / Strong — independent replication of STING K48-ubiquitination mechanism across two labs with in vivo validation","pmids":["29581886"],"is_preprint":false},{"year":2016,"finding":"TRIM29 directly binds NEMO (IKK-γ) and induces its K48-linked ubiquitination and proteasomal degradation, thereby inhibiting both IRF- and NF-κB-mediated signaling in alveolar macrophages.","method":"Co-immunoprecipitation, ubiquitination assay, Trim29-/- mouse model (influenza and H. influenzae challenge), cytokine measurement","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding demonstrated by Co-IP, degradation confirmed biochemically, functional consequences validated in vivo","pmids":["27695001"],"is_preprint":false},{"year":2018,"finding":"TRIM29 interacts with MAVS and induces its K11-linked ubiquitination and proteasomal degradation, negatively regulating type I IFN production in response to dsRNA viruses (reovirus, poly I:C).","method":"Co-immunoprecipitation, ubiquitination assay, Trim29-/- mouse model (reovirus challenge), IFN measurement","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding and ubiquitination demonstrated biochemically with in vivo confirmation in knockout mice","pmids":["29769269"],"is_preprint":false},{"year":2010,"finding":"ATDC/TRIM29 binds p53, sequesters it outside the nucleus, and represses p53-regulated gene expression (p21, NOXA), thereby promoting cell proliferation and resistance to ionizing radiation. This interaction is modulated by acetylation of lysine 116 on ATDC.","method":"Co-immunoprecipitation, reporter gene assays, immunofluorescence (p53 localization), RNAi silencing, cell proliferation assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct binding confirmed, subcellular localization shift demonstrated, functional gene expression readouts, single lab with multiple orthogonal methods","pmids":["20368352"],"is_preprint":false},{"year":2010,"finding":"HDAC9 co-purifies with TRIM29/ATDC and deacetylates it, thereby altering TRIM29's ability to associate with p53 and inhibiting TRIM29's cell proliferation-promoting activity.","method":"Biochemical co-purification, deacetylation assay, co-immunoprecipitation, cell proliferation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — enzymatic deacetylation demonstrated biochemically with functional validation, single lab, multiple methods","pmids":["20947501"],"is_preprint":false},{"year":2011,"finding":"TRIM29 binds Tip60 acetyltransferase (identified by yeast two-hybrid screening), promotes Tip60 degradation and altered localization, and reduces Tip60-mediated acetylation of p53 at lysine 120, thereby suppressing apoptosis and enhancing cell growth.","method":"Yeast two-hybrid, co-immunoprecipitation, Western blot for Tip60 levels, p53-K120 acetylation assay, UV-induced apoptosis assay (HCT116 cells)","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus Co-IP binding, functional acetylation readout, single lab","pmids":["21463657"],"is_preprint":false},{"year":2015,"finding":"TRIM29 functions as a histone-binding scaffold protein that interacts with BRCA1-associated surveillance complex, cohesin, DNA-PKcs, and components of the TIP60 complex, assembling them into damaged chromatin; TRIM29 binding to modified H3 and H4 tails in nucleosomes is required for H2AX phosphorylation and cell viability after ionizing radiation.","method":"Mass spectrometry-based proteomics (MudPIT), co-immunoprecipitation, histone binding assays, chromatin fractionation, γH2AX readout, clonogenic survival after IR","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (MS interactome, Co-IP, in vitro nucleosome binding, functional IR assay) in a single rigorous study","pmids":["26095369"],"is_preprint":false},{"year":2014,"finding":"ATDC/TRIM29 is directly phosphorylated by MAPKAP kinase 2 (MK2) at Serine 550 in an ATM-dependent manner, and this phosphorylation is required for ATDC's radioprotective function in pancreatic cancer cells.","method":"In vitro kinase assay (MK2 phosphorylating ATDC), site-directed mutagenesis (S550 mutants), clonogenic survival after IR, mouse xenograft model","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase assay plus mutagenesis plus functional in vivo xenograft validation, single lab","pmids":["24469230"],"is_preprint":false},{"year":2014,"finding":"ATDC/TRIM29 overexpression in vivo drives both noninvasive and invasive bladder carcinoma in transgenic mice by suppressing miR-29 expression, leading to DNMT3A upregulation, DNA methylation, and silencing of the tumor suppressor PTEN.","method":"Transgenic mouse model (ATDC overexpression), miRNA profiling, DNMT3A and PTEN expression analysis, methylation assays","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — in vivo transgenic model with downstream pathway validation, single lab with multiple methods","pmids":["26471361"],"is_preprint":false},{"year":2014,"finding":"TRIM29 suppresses invasive breast cancer behavior by inhibiting TWIST1 activity; TWIST1 transcriptionally represses TRIM29 expression by directly binding E-box elements in the TRIM29 promoter, establishing a negative regulatory feedback loop.","method":"RNAi silencing, TWIST1 overexpression/knockdown, promoter-luciferase reporter assay with E-box mutation, EMT marker analysis (E/N-cadherin, vimentin, EpCAM)","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase reporter with direct binding evidence, functional EMT phenotype readouts, single lab","pmids":["24950909"],"is_preprint":false},{"year":2019,"finding":"TRIM29 ubiquitinates and degrades TAB2 (TGF-β-activated kinase 1 binding protein 2) in NK cells following activation, thereby negatively regulating IFN-γ production; TRIM29-deficient NK cells produce more IFN-γ and protect mice from murine CMV infection.","method":"Co-immunoprecipitation, ubiquitination assay, TRIM29-specific NK cell knockout mice (CMV challenge), IFN-γ measurement","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding and ubiquitination demonstrated, in vivo NK-specific knockout validation with clear functional phenotype","pmids":["31270148"],"is_preprint":false},{"year":2018,"finding":"Loss of TRIM29 in squamous cell carcinoma cells leads to ectopic keratin localization; TRIM29 interacts with keratins and keratin-interacting protein FAM83H to regulate the keratin distribution network.","method":"Comprehensive proteomics, co-immunoprecipitation, immunofluorescence (keratin localization), TRIM29 knockdown/overexpression migration/invasion assays","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — mass spectrometry interactome plus Co-IP binding, direct localization readout, functional migration assays, single lab","pmids":["30389700"],"is_preprint":false},{"year":2019,"finding":"TRIM29 interacts with IGF2BP1 and induces its K48-linked ubiquitination at Lys440 and Lys450, leading to IGF2BP1 degradation; loss of IGF2BP1 reduces PD-L1 mRNA stability, enhancing anti-tumor T-cell immunity in gastric cancer.","method":"Proteomics, co-immunoprecipitation, in vitro ubiquitination assay (specific lysine sites), PD-L1 3'UTR reporter assay, in vivo tumor model","journal":"Cancer letters","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — site-specific ubiquitination demonstrated biochemically with multiple downstream functional readouts, single lab","pmids":["38029830"],"is_preprint":false},{"year":2024,"finding":"TRIM29 interacts with PERK (protein kinase RNA-like ER kinase) and promotes SUMOylation of PERK to maintain its stability, thereby sustaining PERK-mediated ER stress, apoptosis, and ROS responses that promote viral replication in cardiomyocytes during viral myocarditis.","method":"Co-immunoprecipitation, SUMOylation assay, TRIM29-/- mouse model (cardiotropic virus challenge), PERK inhibitor (GSK2656157) in vivo treatment, cardiac function readouts","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct binding and SUMOylation demonstrated, pharmacological and genetic validation in vivo, single lab with multiple methods","pmids":["38664417"],"is_preprint":false},{"year":2024,"finding":"TRIM29 promotes K48-linked ubiquitination and degradation of both NLRP6 and NLRP9b in intestinal epithelial cells, suppressing IFN-λ and IL-18 production during enteric RNA virus infection, thereby facilitating viral-induced intestinal inflammation.","method":"TRIM29 knockout in intestinal epithelial cells (rotavirus and EMCV models), ubiquitination assay, cytokine measurement (IFN-λ, IL-18), immune cell recruitment analysis","journal":"Mucosal immunology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — K48-ubiquitination of two substrates demonstrated with IEC-specific KO and in vivo viral challenge models","pmids":["39396665"],"is_preprint":false},{"year":2019,"finding":"TRIM29 knockdown in pancreatic cancer cells destabilizes ISG15 protein by promoting its processing via calpain 3 (CAPN3); TRIM29 normally protects ISG15 from CAPN3-mediated cleavage, and extracellular free ISG15 (secreted) maintains cancer stem cell-like features via autocrine signaling.","method":"TRIM29 knockdown, CAPN3 inhibitor treatment, ISG15 stability assays, stem cell sphere formation, rescue experiments with secreted ISG15","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ISG15 stabilization mechanism biochemically characterized, single lab, multiple functional assays","pmids":["31501523"],"is_preprint":false},{"year":2021,"finding":"TRIM29 directly binds YAP1 and reduces its K48-linked ubiquitination and degradation, thereby stabilizing YAP1 and promoting pancreatic cancer cell proliferation.","method":"Co-immunoprecipitation, in vitro ubiquitination assay, YAP1 protein stability analysis, rescue proliferation experiments, mouse xenograft","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding and reduced ubiquitination shown biochemically with in vivo validation, single lab","pmids":["34353343"],"is_preprint":false},{"year":2021,"finding":"TRIM29 promotes degradation of pyruvate kinase M1 (PKM1) via the ubiquitin-proteasome pathway by directly targeting PKM1, reducing the PKM1/PKM2 ratio and promoting PKM2-mediated aerobic glycolysis (Warburg effect) in colorectal cancer.","method":"Co-immunoprecipitation, ubiquitination assay, PKM1/PKM2 ratio analysis, metabolic assays, TRIM29 knockdown/overexpression in vitro and in vivo","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct ubiquitination target identified biochemically with functional metabolic readout, single lab","pmids":["33495406"],"is_preprint":false},{"year":2023,"finding":"TRIM29 interacts with IκBα and mediates its K48-linked ubiquitination-dependent degradation, leading to NF-κB activation and downstream NLRP3 inflammasome-mediated podocyte pyroptosis in diabetic nephropathy.","method":"Co-immunoprecipitation, ubiquitination assay, TRIM29 overexpression/knockdown with NF-κB inhibitor rescue, NLRP3/caspase-1/GSDMD-N Western blot, flow cytometry for pyroptosis","journal":"Cell biology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding and ubiquitination of IκBα demonstrated, functional pathway rescue, single lab","pmids":["36841942"],"is_preprint":false},{"year":2023,"finding":"TRIM29 interacts with NLRC4 inflammasome protein and promotes its K48-linked polyubiquitination and proteasomal degradation in neurons and microglia, thereby reducing NLRC4 inflammasome activation and limiting neuronal injury in ischemic stroke.","method":"Co-immunoprecipitation with truncation mutants, ubiquitination assay, TRIM29 knockout mice (MCAO model), immunofluorescence for apoptosis/pyroptosis, cytokine measurement","journal":"Stroke","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain-mapping Co-IP plus ubiquitination assay with in vivo KO model, single lab","pmids":["37021569"],"is_preprint":false},{"year":2015,"finding":"TRIM29 is required for regulation of the p63 (TAp63α)-mediated pathway in cervical cancer cells; TRIM29 controls TAp63α expression levels and modulates integrin expression and ZEB1 to regulate cell adhesion and invasion.","method":"TRIM29 knockdown and overexpression, TAp63α expression analysis, integrin profiling, cell adhesion and invasion assays","journal":"Biochimica et biophysica acta","confidence":"Low","confidence_rationale":"Tier 3 / Weak — functional phenotype with gene expression readouts but no direct binding or ubiquitination assay shown for p63, single lab","pmids":["26071105"],"is_preprint":false},{"year":2020,"finding":"TRIM29 is required for efficient recruitment of 53BP1 to DNA double-strand break sites; TRIM29 knockout cells show impaired 53BP1 foci formation after etoposide, reduced NHEJ efficiency, and compensatory upregulation of RAD51-mediated homologous recombination.","method":"Gene targeting (homologous recombination) in DT40 cells, clonogenic survival assays, immunofluorescence for γH2AX, 53BP1, and RAD51 foci","journal":"FEBS open bio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with defined DSB repair pathway readouts, multiple repair markers assessed","pmids":["33017104"],"is_preprint":false},{"year":2025,"finding":"USP18 interacts with TRIM29 and facilitates its K27-linked ubiquitination by recruiting TRIM21 (which directly ubiquitinates TRIM29 at Lys561); this promotes TRIM29 oligomerization and nuclear translocation, enhancing DNA damage response and radioresistance in nasopharyngeal carcinoma cells.","method":"Co-immunoprecipitation, ubiquitination assay (site-specific K561 mutant), immunofluorescence for nuclear translocation, radiosensitivity assays","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — site-specific ubiquitination mapped, nuclear translocation shown, functional radioresistance readout, single lab","pmids":["41219493"],"is_preprint":false},{"year":2023,"finding":"TRIM29 interacts with VDAC1 to activate mitophagy, which clears damaged mitochondria and reduces ROS accumulation, thereby preventing cellular senescence in nasopharyngeal carcinoma cells.","method":"Co-immunoprecipitation, TRIM29 silencing with ROS measurement, mitophagy assays, cellular senescence assays, in vivo tumor growth","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding demonstrated, mechanistic link to mitophagy and ROS established, single lab","pmids":["37248790"],"is_preprint":false},{"year":2025,"finding":"TRIM29 promotes K48-linked ubiquitination and proteasomal degradation of PRRSV nsp11 (binding via TRIM29's coiled-coil domain at conserved catalytic residue K173), thereby inhibiting nsp11's suppression of IFN-β and restricting PRRSV replication.","method":"Co-immunoprecipitation, in vitro ubiquitination assay (K173R mutant), domain-mapping experiments, IFN-β reporter assays, viral replication assays","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — direct binding domain mapped, site-specific ubiquitination demonstrated, functional IFN and viral replication readouts, single lab","pmids":["41251350"],"is_preprint":false},{"year":2025,"finding":"TRIM29 physically interacts with K14+ intermediate filaments in bladder cancer cells, and this interaction regulates focal adhesion stability (requiring ZYX) to drive cancer cell migration and invasion.","method":"Co-immunoprecipitation, KD/KO functional assays (migration, invasion), focal adhesion analysis, K14 and ZYX knockdown rescue experiments","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein interaction demonstrated, epistasis with K14/ZYX established, single lab","pmids":["40908312"],"is_preprint":false},{"year":2024,"finding":"O-GlcNAcylation of TRIM29 at threonine 120 (T120) is required for TRIM29-mediated adaptive responses of pancreatic cancer cells to glucose deficiency; TRIM29 and OGT form a feedback loop where OGT O-GlcNAcylates TRIM29, and TRIM29 promotes OGT translation.","method":"Western blot, mass spectrometry, WGA-immunoprecipitation, T120 site mutagenesis, protein stability and translation assays under glucose deprivation, crystal violet/flow cytometry functional assays","journal":"Cellular oncology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — site-specific PTM mapped by MS and mutagenesis, feedback mechanism demonstrated biochemically, single lab","pmids":["38345749"],"is_preprint":false},{"year":2025,"finding":"TRIM29 degrades YBX1 through K48-linked ubiquitination, thereby inhibiting the PI3K/AKT signaling pathway and reversing lenvatinib resistance in hepatocellular carcinoma.","method":"Co-immunoprecipitation, mass spectrometry, transcriptome sequencing, ubiquitination assay, colony formation/CCK8/flow cytometry, in vivo xenograft","journal":"Translational oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding and ubiquitination demonstrated with in vivo validation, single lab","pmids":["39874728"],"is_preprint":false},{"year":2016,"finding":"TRIM29 expression in breast tumor and non-tumorigenic mammary cells is negatively regulated by ATM: basal TRIM29 levels depend on NF-κB (RelA subunit) activity, and hypoxia-induced TRIM29 upregulation requires both ATM and HIF1α through increased TRIM29 gene transcription.","method":"ATM knockdown, RelA knockdown, HIF1α inhibition, hypoxia treatment, TRIM29 promoter-reporter assays, Western blot","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis established through genetic knockdowns, transcriptional mechanism confirmed, single lab","pmids":["27535224"],"is_preprint":false},{"year":2021,"finding":"TRIM29 maintains cancer stem cell-like features in ovarian cancer by facilitating SETBP1 transcriptional activation through the VEZF1 transcription factor; TRIM29 promotes VEZF1 mRNA translation by recruiting RNA-binding protein BICC1 to the VEZF1 3'UTR, and the SETBP1/SET/PP2A axis downstream mediates the CSC phenotype.","method":"Global proteomics, co-immunoprecipitation, RNA-immunoprecipitation (RIP), luciferase reporter, TRIM29 KD rescue experiments","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomics-driven pathway with biochemical validation of BICC1/VEZF1/SETBP1 interactions, single lab","pmids":["34973391"],"is_preprint":false},{"year":2025,"finding":"TRIM29 interacts with FAM83H, stabilizes it by reducing its ubiquitination and degradation, thereby redistributing cellular keratins, activating NF-κB, upregulating PLXNB2, and enhancing CRC cell adhesion and liver metastatic colonization.","method":"Multi-omics, co-immunoprecipitation, ubiquitination assay, FAM83H stability analysis, NF-κB and PLXNB2 pathway readouts, in vivo metastasis model","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding and de-ubiquitination (stabilization) mechanism demonstrated with downstream pathway validation in vivo, single lab","pmids":["40389046"],"is_preprint":false},{"year":2024,"finding":"tRF-AspGTC binds galectin-3 and inhibits TRIM29-mediated ubiquitination of galectin-3, thereby stabilizing galectin-3, which activates TLR4/MyD88/NF-κB signaling to drive vascular smooth muscle cell phenotypic switching and intracranial aneurysm formation.","method":"Co-immunoprecipitation, ubiquitination assay, tRF-AspGTC gain/loss of function, galectin-3 stability assays, TLR4/NF-κB pathway readouts","journal":"Research (Washington, D.C.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TRIM29-mediated ubiquitination substrate identified with functional modulation demonstrated, single lab","pmids":["39776588"],"is_preprint":false},{"year":2021,"finding":"KLF4 binds a specific site in the TRIM29 promoter to transactivate its transcription, and KLF4-driven TRIM29 expression mediates KLF4-induced cell migration and modulation of the keratin network (keratin 8 phosphorylation at aa 432).","method":"Promoter-luciferase assay, ChIP or promoter binding assay, TRIM29 knockdown rescue of KLF4-induced migration, Western blot for KRT8 phosphorylation","journal":"Biochemistry and biophysics reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — promoter transactivation shown but binding assay details limited in abstract, single lab","pmids":["34485714"],"is_preprint":false},{"year":2024,"finding":"TRIM29 promotes PHLPP1 K48-linked ubiquitination and degradation in pancreatic ductal adenocarcinoma; TRIM29 is recruited by NAP1L5 which binds PHLPP1, and the resulting PHLPP1 degradation activates AKT/mTOR signaling.","method":"Co-immunoprecipitation, ubiquitination assay, PHLPP1 stability analysis, NAP1L5/TRIM29 knockdown, AKT/mTOR pathway readouts","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TRIM29 as ubiquitin ligase for PHLPP1 biochemically demonstrated, single lab with multiple methods","pmids":["37717692"],"is_preprint":false},{"year":2026,"finding":"TRIM29 directly binds IκBα via its BB2 domain and catalyzes K48-linked ubiquitination and proteasomal degradation of IκBα, activating NF-κB signaling and promoting EMT in CXCL5+ pancreatic cancer cells to drive microvascular invasion.","method":"Co-immunoprecipitation (domain mapping), ubiquitination assay, ChIP-qPCR, migration/invasion assays, xenograft model","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain-mapped binding and site-specific ubiquitination demonstrated biochemically with in vivo validation, single lab","pmids":["41952208"],"is_preprint":false}],"current_model":"TRIM29 is a RING-less E3 ubiquitin ligase (using its B-box domain) that acts as an inducible negative regulator of innate immunity by targeting key immune adaptors—STING, NEMO, MAVS, NLRP6, NLRP9b, TAB2, and NLRC4—for K48-linked polyubiquitination and proteasomal degradation; in cancer, TRIM29 also scaffolds DNA repair complexes at chromatin, sequesters p53 from the nucleus (regulated by HDAC9-mediated deacetylation and MK2/ATM-mediated phosphorylation at Ser550), suppresses Tip60-mediated p53-K120 acetylation, stabilizes oncoproteins (YAP1, EZH2, FAM83H, ISG15) by reducing their ubiquitination, and regulates keratin network distribution by binding K14/K5 intermediate filaments and FAM83H to control cell migration and invasion."},"narrative":{"mechanistic_narrative":"TRIM29 is a B-box-dependent E3 ubiquitin ligase that functions as an inducible negative regulator of innate antiviral immunity and, separately, as a chromatin-associated scaffold and oncogenic stabilizer/destabilizer of cellular substrates. In immune cells, TRIM29 directly binds and ubiquitinates core signaling adaptors to terminate interferon and inflammatory responses: it drives K48-linked ubiquitination and proteasomal degradation of STING to shut down cytosolic dsDNA sensing [PMID:29038422, PMID:29581886], NEMO to block both IRF and NF-κB output [PMID:27695001], MAVS via K11-linked chains to suppress RNA-virus-induced type I IFN [PMID:29769269], TAB2 in NK cells to limit IFN-γ [PMID:31270148], and NLRP6/NLRP9b in intestinal epithelium to dampen IFN-λ and IL-18 [PMID:39396665]; loss of TRIM29 in these settings enhances antiviral and inflammasome responses [PMID:29581886, PMID:39396665, PMID:37021569]. In the DNA damage response, TRIM29 acts as a histone-binding scaffold that assembles BRCA1-associated surveillance, cohesin, DNA-PKcs and TIP60 complexes onto damaged chromatin, supporting H2AX phosphorylation and clonogenic survival after ionizing radiation [PMID:26095369], and is required for 53BP1 recruitment and efficient NHEJ [PMID:33017104]. Its radioprotective scaffolding activity is licensed by MK2/ATM-dependent phosphorylation at Ser550 [PMID:24469230] and by USP18/TRIM21-mediated K27-linked ubiquitination at Lys561 that triggers oligomerization and nuclear translocation [PMID:41219493]. TRIM29 also restrains the p53 axis—sequestering p53 outside the nucleus to repress p21/NOXA [PMID:20368352] and degrading the acetyltransferase Tip60 to reduce p53-K120 acetylation and apoptosis [PMID:21463657]—with HDAC9 deacetylation modulating its p53 association [PMID:20947501]. Across cancers TRIM29 selectively controls substrate stability, degrading tumor-suppressive or restraining factors such as IκBα to activate NF-κB-driven EMT [PMID:41952208, PMID:36841942], PHLPP1 to activate AKT/mTOR [PMID:37717692], IGF2BP1, YBX1 and PKM1 [PMID:38029830, PMID:39874728, PMID:33495406], while stabilizing oncogenic clients including YAP1, FAM83H and ISG15 by limiting their ubiquitination [PMID:34353343, PMID:40389046, PMID:31501523]. Through binding K14 intermediate filaments and FAM83H it reorganizes the keratin network and focal adhesions to promote migration and invasion [PMID:30389700, PMID:40908312, PMID:40389046].","teleology":[{"year":2010,"claim":"Established the first mechanistic role for TRIM29 in cancer: how it could promote proliferation and radioresistance by neutralizing p53, and how that activity is regulated by acetylation.","evidence":"Co-IP, p53 localization imaging and reporter assays plus HDAC9 deacetylation assay in cancer cells","pmids":["20368352","20947501"],"confidence":"High","gaps":["Mechanism of cytoplasmic p53 retention not structurally defined","Whether TRIM29 ubiquitinates p53 directly not addressed"]},{"year":2011,"claim":"Extended p53 regulation by showing TRIM29 degrades the Tip60 acetyltransferase, linking TRIM29 to suppression of p53-K120 acetylation and apoptosis.","evidence":"Yeast two-hybrid, Co-IP, and p53-K120 acetylation/apoptosis readouts in HCT116 cells","pmids":["21463657"],"confidence":"Medium","gaps":["Direct ubiquitination of Tip60 by TRIM29 not biochemically isolated","Single lab"]},{"year":2014,"claim":"Defined the upstream signals and downstream oncogenic outputs of TRIM29: MK2/ATM phosphorylation at Ser550 enables radioprotection, while overexpression drives bladder carcinoma via miR-29/DNMT3A/PTEN silencing and restrains breast cancer through a TWIST1 feedback loop.","evidence":"In vitro kinase assay with S550 mutagenesis, transgenic mouse tumor models, and promoter-reporter/EMT assays","pmids":["24469230","26471361","24950909"],"confidence":"High","gaps":["Context-dependent oncogenic vs tumor-suppressive roles not reconciled","How S550 phosphorylation alters substrate engagement unknown"]},{"year":2015,"claim":"Reframed TRIM29 as a histone-binding chromatin scaffold, explaining its radioprotection mechanistically by showing it assembles DNA repair complexes onto damaged nucleosomes to enable H2AX phosphorylation.","evidence":"MudPIT interactome, in vitro nucleosome/histone binding, chromatin fractionation, and clonogenic IR survival","pmids":["26095369"],"confidence":"High","gaps":["Histone-mark specificity not fully mapped","Relationship of scaffolding to its E3 ligase activity unresolved"]},{"year":2016,"claim":"Identified TRIM29 as a NEMO-degrading immune brake and clarified its own transcriptional control by ATM/NF-κB/HIF1α, establishing the negative-regulator-of-innate-immunity paradigm and its inducibility.","evidence":"Co-IP, ubiquitination assay, Trim29-/- influenza/H. influenzae challenge; ATM/RelA/HIF1α knockdown with promoter reporters","pmids":["27695001","27535224"],"confidence":"High","gaps":["Whether immune and DNA-repair functions are mutually exclusive in a given cell not addressed"]},{"year":2018,"claim":"Generalized TRIM29 as an adaptor-degrading immune suppressor across sensing pathways by demonstrating K48-ubiquitination of STING and K11-ubiquitination of MAVS, controlling DNA- and RNA-virus responses.","evidence":"Ubiquitination assays and Trim29-/- mouse infection models (HSV-1, reovirus) with IFN readouts","pmids":["29581886","29769269","29038422"],"confidence":"High","gaps":["Determinants of K48 vs K11 chain choice not defined","B-box catalytic mechanism not structurally resolved"]},{"year":2019,"claim":"Broadened TRIM29 immune and oncogenic substrate scope: TAB2 degradation in NK cells limits IFN-γ, IGF2BP1 degradation enhances anti-tumor immunity via PD-L1 mRNA, and TRIM29 protects ISG15 from CAPN3 cleavage to sustain stemness.","evidence":"NK-specific KO CMV model, site-specific ubiquitination assays, and ISG15 stability/sphere assays","pmids":["31270148","38029830","31501523"],"confidence":"High","gaps":["How TRIM29 switches between degrading and stabilizing substrates unknown"]},{"year":2021,"claim":"Demonstrated TRIM29 substrate stabilization as an oncogenic mechanism (YAP1) and metabolic rewiring (PKM1 degradation shifting toward PKM2/Warburg), alongside RNA-level CSC control via VEZF1/BICC1.","evidence":"Co-IP, ubiquitination assays, metabolic and proliferation assays, RIP and xenografts","pmids":["34353343","33495406","34973391"],"confidence":"Medium","gaps":["Single labs per substrate","Direct vs indirect ubiquitination not always distinguished"]},{"year":2023,"claim":"Connected TRIM29's E3 activity to NF-κB and inflammasome control in disease contexts: IκBα degradation drives podocyte pyroptosis, NLRC4 degradation limits stroke injury, while VDAC1-driven mitophagy suppresses senescence.","evidence":"Co-IP/domain mapping, ubiquitination assays, KO mouse models (MCAO), and mitophagy/ROS assays","pmids":["36841942","37021569","37248790"],"confidence":"Medium","gaps":["Opposing NF-κB effects (activation via IκBα vs suppression via NEMO) context-dependence unresolved","Single labs"]},{"year":2024,"claim":"Revealed additional regulatory layers and substrates: O-GlcNAcylation at T120 and an OGT feedback loop support glucose-stress adaptation, PERK SUMOylation sustains ER stress in myocarditis, PHLPP1 degradation activates AKT/mTOR, and NLRP6/NLRP9b degradation shapes intestinal antiviral immunity.","evidence":"MS-mapped PTM site mutagenesis, SUMOylation/ubiquitination assays, and KO mouse viral/metabolic models","pmids":["38345749","38664417","37717692","39396665"],"confidence":"Medium","gaps":["Hierarchy of PTMs governing TRIM29 activity not integrated","Tissue-specific substrate selection unexplained"]},{"year":2025,"claim":"Mapped TRIM29 activation and effector mechanisms: USP18/TRIM21 K27-ubiquitination at K561 drives nuclear translocation/radioresistance, BB2-domain-dependent IκBα degradation drives pancreatic EMT, coiled-coil targeting of PRRSV nsp11 restricts virus, and K14/ZYX-coupled focal adhesion control plus FAM83H stabilization drive invasion/metastasis.","evidence":"Domain-mapping Co-IP, site-specific ubiquitination assays, nuclear translocation imaging, and in vivo invasion/metastasis models","pmids":["41219493","41952208","41251350","40908312","40389046","39874728"],"confidence":"Medium","gaps":["Structural basis of B-box/coiled-coil substrate recognition still lacking","Single labs per substrate"]},{"year":null,"claim":"How TRIM29 selects between K48, K11, and K27 chain types and between degradative versus stabilizing outcomes for its many substrates, and how its immune-suppressive and DNA-repair scaffolding functions are coordinated within a cell, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the B-box catalytic mechanism","No unifying rule for substrate fate (degrade vs stabilize)","Cross-talk between immune and chromatin roles uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,1,2,3,11,13,15,20,35]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,2,3,13,15,20,34,35]},{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[0,2,13,35]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[7,12,26]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[12,26]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[16,17,31]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[4,23]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[7,22]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[4,12]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[12,26]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,1,2,3,11,15]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[7,22]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,2,13,17,34,35]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[19,34,35]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[9,19,32]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[18,27]}],"complexes":["TIP60 complex","BRCA1-associated surveillance complex"],"partners":["STING1","NEMO","MAVS","TAB2","FAM83H","YAP1","IGF2BP1","PERK"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q14134","full_name":"Tripartite motif-containing protein 29","aliases":["Ataxia telangiectasia group D-associated protein"],"length_aa":588,"mass_kda":65.8,"function":"Plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. Mechanistically, TRIM29 interacts with IKBKG/NEMO in the lysosome where it induces its 'Lys-48' ubiquitination and subsequent degradation. In turn, the expression of type I interferons and the production of pro-inflammatory cytokines are inhibited. Additionally, induces the 'Lys-48' ubiquitination of STING1 in a similar way, leading to its degradation","subcellular_location":"Cytoplasm; Lysosome","url":"https://www.uniprot.org/uniprotkb/Q14134/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TRIM29","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TRIM29","total_profiled":1310},"omim":[{"mim_id":"610658","title":"TRIPARTITE MOTIF-CONTAINING PROTEIN 29; TRIM29","url":"https://www.omim.org/entry/610658"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Intermediate filaments","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"esophagus","ntpm":699.7},{"tissue":"skin 1","ntpm":719.7},{"tissue":"vagina","ntpm":361.7}],"url":"https://www.proteinatlas.org/search/TRIM29"},"hgnc":{"alias_symbol":["ATDC","FLJ36085"],"prev_symbol":[]},"alphafold":{"accession":"Q14134","domains":[{"cath_id":"-","chopping":"170-223","consensus_level":"medium","plddt":86.0646,"start":170,"end":223}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14134","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q14134-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q14134-F1-predicted_aligned_error_v6.png","plddt_mean":61.47},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TRIM29","jax_strain_url":"https://www.jax.org/strain/search?query=TRIM29"},"sequence":{"accession":"Q14134","fasta_url":"https://rest.uniprot.org/uniprotkb/Q14134.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q14134/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14134"}},"corpus_meta":[{"pmid":"29038422","id":"PMC_29038422","title":"TRIM29 promotes DNA virus infections by inhibiting innate immune response.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29038422","citation_count":215,"is_preprint":false},{"pmid":"27695001","id":"PMC_27695001","title":"Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract.","date":"2016","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/27695001","citation_count":170,"is_preprint":false},{"pmid":"29581886","id":"PMC_29581886","title":"TRIM29 negatively controls antiviral immune response through targeting STING for degradation.","date":"2018","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/29581886","citation_count":134,"is_preprint":false},{"pmid":"33011193","id":"PMC_33011193","title":"m6A-YTHDF1-mediated TRIM29 upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells.","date":"2020","source":"Biochimica et biophysica acta. Molecular cell research","url":"https://pubmed.ncbi.nlm.nih.gov/33011193","citation_count":116,"is_preprint":false},{"pmid":"20368352","id":"PMC_20368352","title":"The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions.","date":"2010","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/20368352","citation_count":107,"is_preprint":false},{"pmid":"34922544","id":"PMC_34922544","title":"CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer.","date":"2021","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/34922544","citation_count":100,"is_preprint":false},{"pmid":"17597343","id":"PMC_17597343","title":"Tripartite motif-containing 29 (TRIM29) is a novel marker for lymph node metastasis in gastric cancer.","date":"2007","source":"Annals of surgical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/17597343","citation_count":95,"is_preprint":false},{"pmid":"38664417","id":"PMC_38664417","title":"Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38664417","citation_count":89,"is_preprint":false},{"pmid":"24950909","id":"PMC_24950909","title":"TRIM29 suppresses TWIST1 and invasive breast cancer behavior.","date":"2014","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/24950909","citation_count":83,"is_preprint":false},{"pmid":"21463657","id":"PMC_21463657","title":"TRIM29 negatively regulates p53 via inhibition of Tip60.","date":"2011","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/21463657","citation_count":79,"is_preprint":false},{"pmid":"29769269","id":"PMC_29769269","title":"TRIM29 Negatively Regulates the Type I IFN Production in Response to RNA Virus.","date":"2018","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/29769269","citation_count":76,"is_preprint":false},{"pmid":"26191199","id":"PMC_26191199","title":"TRIM29 functions as an oncogene in gastric cancer and is regulated by miR-185.","date":"2015","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26191199","citation_count":68,"is_preprint":false},{"pmid":"20947501","id":"PMC_20947501","title":"Histone deacetylase 9 (HDAC9) regulates the functions of the ATDC (TRIM29) protein.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20947501","citation_count":67,"is_preprint":false},{"pmid":"26471361","id":"PMC_26471361","title":"ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms.","date":"2015","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/26471361","citation_count":64,"is_preprint":false},{"pmid":"26872369","id":"PMC_26872369","title":"Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/26872369","citation_count":61,"is_preprint":false},{"pmid":"26095369","id":"PMC_26095369","title":"TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26095369","citation_count":60,"is_preprint":false},{"pmid":"30876939","id":"PMC_30876939","title":"MicroRNA-424-5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29.","date":"2019","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30876939","citation_count":59,"is_preprint":false},{"pmid":"38029830","id":"PMC_38029830","title":"TRIM29 promotes antitumor immunity through enhancing IGF2BP1 ubiquitination and subsequent PD-L1 downregulation in gastric cancer.","date":"2023","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/38029830","citation_count":57,"is_preprint":false},{"pmid":"24469230","id":"PMC_24469230","title":"ATDC/TRIM29 phosphorylation by ATM/MAPKAP kinase 2 mediates radioresistance in pancreatic cancer cells.","date":"2014","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/24469230","citation_count":55,"is_preprint":false},{"pmid":"30813948","id":"PMC_30813948","title":"TRIM29 facilitates the epithelial-to-mesenchymal transition and the progression of colorectal cancer via the activation of the Wnt/β-catenin signaling pathway.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/30813948","citation_count":53,"is_preprint":false},{"pmid":"22138580","id":"PMC_22138580","title":"TRIM29 functions as a tumor suppressor in nontumorigenic breast cells and invasive ER+ breast cancer.","date":"2011","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/22138580","citation_count":52,"is_preprint":false},{"pmid":"28098872","id":"PMC_28098872","title":"TRIM29 promotes progression of thyroid carcinoma via activating P13K/AKT signaling pathway.","date":"2017","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/28098872","citation_count":51,"is_preprint":false},{"pmid":"26987391","id":"PMC_26987391","title":"TRIM29 Overexpression Promotes Proliferation and Survival of Bladder Cancer Cells through NF-κB Signaling.","date":"2016","source":"Cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/26987391","citation_count":50,"is_preprint":false},{"pmid":"24485335","id":"PMC_24485335","title":"TRIM29 as a novel prostate basal cell marker for diagnosis of prostate cancer.","date":"2014","source":"Acta histochemica","url":"https://pubmed.ncbi.nlm.nih.gov/24485335","citation_count":46,"is_preprint":false},{"pmid":"30389700","id":"PMC_30389700","title":"Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma.","date":"2018","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/30389700","citation_count":42,"is_preprint":false},{"pmid":"27430345","id":"PMC_27430345","title":"RNA interference against TRIM29 inhibits migration and invasion of colorectal cancer cells.","date":"2016","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/27430345","citation_count":42,"is_preprint":false},{"pmid":"31270148","id":"PMC_31270148","title":"Identification of the E3 Ligase TRIM29 as a Critical Checkpoint Regulator of NK Cell Functions.","date":"2019","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/31270148","citation_count":41,"is_preprint":false},{"pmid":"28054302","id":"PMC_28054302","title":"microRNA-761 induces aggressive phenotypes in triple-negative breast cancer cells by repressing TRIM29 expression.","date":"2017","source":"Cellular oncology (Dordrecht, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/28054302","citation_count":41,"is_preprint":false},{"pmid":"31501523","id":"PMC_31501523","title":"Loss of TRIM29 suppresses cancer stem cell-like characteristics of PDACs via accelerating ISG15 degradation.","date":"2019","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/31501523","citation_count":40,"is_preprint":false},{"pmid":"22721621","id":"PMC_22721621","title":"Significance of TRIM29 and β-catenin expression in non-small-cell lung cancer.","date":"2012","source":"Journal of the Chinese Medical Association : JCMA","url":"https://pubmed.ncbi.nlm.nih.gov/22721621","citation_count":37,"is_preprint":false},{"pmid":"32640423","id":"PMC_32640423","title":"TRIM29 mediates lung squamous cell carcinoma cell metastasis by regulating autophagic degradation of E-cadherin.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/32640423","citation_count":36,"is_preprint":false},{"pmid":"30566565","id":"PMC_30566565","title":"TRIM29 prevents hepatocellular carcinoma progression by inhibiting Wnt/β-catenin signaling pathway.","date":"2019","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/30566565","citation_count":34,"is_preprint":false},{"pmid":"34973391","id":"PMC_34973391","title":"TRIM29 regulates the SETBP1/SET/PP2A axis via transcription factor VEZF1 to promote progression of ovarian cancer.","date":"2021","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/34973391","citation_count":33,"is_preprint":false},{"pmid":"39396665","id":"PMC_39396665","title":"TRIM29 controls enteric RNA virus-induced intestinal inflammation by targeting NLRP6 and NLRP9b signaling pathways.","date":"2024","source":"Mucosal immunology","url":"https://pubmed.ncbi.nlm.nih.gov/39396665","citation_count":29,"is_preprint":false},{"pmid":"38518727","id":"PMC_38518727","title":"TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770-5p axis in PDAC.","date":"2024","source":"Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/38518727","citation_count":28,"is_preprint":false},{"pmid":"24864129","id":"PMC_24864129","title":"TRIM29 as a novel biomarker in pancreatic adenocarcinoma.","date":"2014","source":"Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/24864129","citation_count":28,"is_preprint":false},{"pmid":"33495406","id":"PMC_33495406","title":"Transcriptional dysregulation of TRIM29 promotes colorectal cancer carcinogenesis via pyruvate kinase-mediated glucose metabolism.","date":"2021","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/33495406","citation_count":28,"is_preprint":false},{"pmid":"27535224","id":"PMC_27535224","title":"The Breast Cancer Tumor Suppressor TRIM29 Is Expressed via ATM-dependent Signaling in Response to Hypoxia.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27535224","citation_count":27,"is_preprint":false},{"pmid":"36841942","id":"PMC_36841942","title":"TRIM29 promotes podocyte pyroptosis in diabetic nephropathy through the NF-kB/NLRP3 inflammasome pathway.","date":"2023","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/36841942","citation_count":26,"is_preprint":false},{"pmid":"32994394","id":"PMC_32994394","title":"TRIM29 inhibits miR-873-5P biogenesis via CYTOR to upregulate fibronectin 1 and promotes invasion of papillary thyroid cancer cells.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/32994394","citation_count":26,"is_preprint":false},{"pmid":"32901838","id":"PMC_32901838","title":"Long non‑coding RNA TP73‑AS1 accelerates the progression and cisplatin resistance of non‑small cell lung cancer by upregulating the expression of TRIM29 via competitively targeting microRNA‑34a‑5p.","date":"2020","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/32901838","citation_count":24,"is_preprint":false},{"pmid":"34353343","id":"PMC_34353343","title":"E3 ubiquitin ligase TRIM29 promotes pancreatic cancer growth and progression via stabilizing Yes-associated protein 1.","date":"2021","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34353343","citation_count":23,"is_preprint":false},{"pmid":"31814890","id":"PMC_31814890","title":"LncRNA HOXA11-AS accumulation-induced microRNA-761 downregulation regulates cell growth by targeting TRIM29 in papillary thyroid cancer.","date":"2019","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/31814890","citation_count":23,"is_preprint":false},{"pmid":"26071105","id":"PMC_26071105","title":"TRIM29 regulates the p63-mediated pathway in cervical cancer cells.","date":"2015","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/26071105","citation_count":21,"is_preprint":false},{"pmid":"29693120","id":"PMC_29693120","title":"MicroRNA‑122 acts as tumor suppressor by targeting TRIM29 and blocking the activity of PI3K/AKT signaling in nasopharyngeal carcinoma in vitro.","date":"2018","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/29693120","citation_count":21,"is_preprint":false},{"pmid":"39776588","id":"PMC_39776588","title":"tRF-AspGTC Promotes Intracranial Aneurysm Formation by Controlling TRIM29-Mediated Galectin-3 Ubiquitination.","date":"2025","source":"Research (Washington, D.C.)","url":"https://pubmed.ncbi.nlm.nih.gov/39776588","citation_count":19,"is_preprint":false},{"pmid":"37021569","id":"PMC_37021569","title":"TRIM29 (Tripartite Motif Containing 29) Alleviates NLRC4 (NLR Family CARD Domain Containing Protein 4) Inflammasome Related Cerebral Injury via Promoting Proteasomal Degradation of NLRC4 in Ischemic Stroke.","date":"2023","source":"Stroke","url":"https://pubmed.ncbi.nlm.nih.gov/37021569","citation_count":16,"is_preprint":false},{"pmid":"29228692","id":"PMC_29228692","title":"Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29228692","citation_count":16,"is_preprint":false},{"pmid":"34988104","id":"PMC_34988104","title":"TRIM29 in Cutaneous Squamous Cell Carcinoma.","date":"2021","source":"Frontiers in medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34988104","citation_count":15,"is_preprint":false},{"pmid":"33898107","id":"PMC_33898107","title":"TRIM29 alters bioenergetics of pancreatic cancer cells via cooperation of miR-2355-3p and DDX3X recruitment to AK4 transcript.","date":"2021","source":"Molecular therapy. Nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/33898107","citation_count":14,"is_preprint":false},{"pmid":"33318312","id":"PMC_33318312","title":"Suppression of long noncoding RNA LINC00324 restricts cell proliferation and invasion of papillary thyroid carcinoma through downregulation of TRIM29 via upregulating microRNA-195-5p.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/33318312","citation_count":13,"is_preprint":false},{"pmid":"36876422","id":"PMC_36876422","title":"lncRNA ELFN1-AS1 upregulates TRIM29 by suppressing miR-211-3p to promote gastric cancer progression.","date":"2023","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/36876422","citation_count":11,"is_preprint":false},{"pmid":"37365152","id":"PMC_37365152","title":"TRIM29 hypermethylation drives esophageal cancer progression via suppression of ZNF750.","date":"2023","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/37365152","citation_count":11,"is_preprint":false},{"pmid":"34624052","id":"PMC_34624052","title":"Combined serum anti-SSA/Ro and salivary TRIM29 reveals promising high diagnostic accuracy in patients with primary Sjögren's syndrome.","date":"2021","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/34624052","citation_count":11,"is_preprint":false},{"pmid":"34790743","id":"PMC_34790743","title":"miR-34c-5p mediates the cellular malignant behaviors of oral squamous cell carcinoma through targeted binding of TRIM29.","date":"2021","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34790743","citation_count":11,"is_preprint":false},{"pmid":"39644332","id":"PMC_39644332","title":"TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond.","date":"2024","source":"Cancer metastasis reviews","url":"https://pubmed.ncbi.nlm.nih.gov/39644332","citation_count":10,"is_preprint":false},{"pmid":"39874728","id":"PMC_39874728","title":"TRIM29 reverses lenvatinib resistance in liver cancer cells by ubiquitinating and degrading YBX1 to inhibit the PI3K/AKT pathway.","date":"2025","source":"Translational oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39874728","citation_count":10,"is_preprint":false},{"pmid":"33824865","id":"PMC_33824865","title":"TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell.","date":"2021","source":"Canadian journal of gastroenterology & hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/33824865","citation_count":10,"is_preprint":false},{"pmid":"35054873","id":"PMC_35054873","title":"Identification of a Novel Oncogenic Fusion Gene SPON1-TRIM29 in Clinical Ovarian Cancer That Promotes Cell and Tumor Growth and Enhances Chemoresistance in A2780 Cells.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35054873","citation_count":10,"is_preprint":false},{"pmid":"38837682","id":"PMC_38837682","title":"LncRNA PVT1 facilitates the growth and metastasis of colorectal cancer by sponging with miR-3619-5p to regulate TRIM29 expression.","date":"2024","source":"Cancer reports (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/38837682","citation_count":9,"is_preprint":false},{"pmid":"22490895","id":"PMC_22490895","title":"[Predicative value of expression of TrkB and TRIM29 in biopsy tissues from preoperative gastroscopy in lymph node metastasis of gastric cancer].","date":"2012","source":"Zhonghua yi xue za zhi","url":"https://pubmed.ncbi.nlm.nih.gov/22490895","citation_count":9,"is_preprint":false},{"pmid":"37671092","id":"PMC_37671092","title":"TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5.","date":"2023","source":"Open life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37671092","citation_count":8,"is_preprint":false},{"pmid":"36685538","id":"PMC_36685538","title":"Duck TRIM29 negatively regulates type I IFN production by targeting MAVS.","date":"2023","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36685538","citation_count":7,"is_preprint":false},{"pmid":"39755113","id":"PMC_39755113","title":"Role of TRIM29 in disease: What is and is not known.","date":"2025","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/39755113","citation_count":6,"is_preprint":false},{"pmid":"40617179","id":"PMC_40617179","title":"TRIM29 promotes glioblastoma progression via ubiquitinating NEFL and activating the PI3K/AKT signaling pathway.","date":"2025","source":"Cancer genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40617179","citation_count":6,"is_preprint":false},{"pmid":"35845310","id":"PMC_35845310","title":"Clinical significance of TRIM29 expression in patients with gastric cancer.","date":"2022","source":"Gastroenterology and hepatology from bed to bench","url":"https://pubmed.ncbi.nlm.nih.gov/35845310","citation_count":6,"is_preprint":false},{"pmid":"37248790","id":"PMC_37248790","title":"TRIM29 acts as a potential senescence suppressor with epigenetic activation in nasopharyngeal carcinoma.","date":"2023","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/37248790","citation_count":6,"is_preprint":false},{"pmid":"33017104","id":"PMC_33017104","title":"TRIM29 is required for efficient recruitment of 53BP1 in response to DNA double-strand breaks in vertebrate cells.","date":"2020","source":"FEBS open bio","url":"https://pubmed.ncbi.nlm.nih.gov/33017104","citation_count":6,"is_preprint":false},{"pmid":"37219039","id":"PMC_37219039","title":"TRIM29 facilitates proliferation and malignancy of cholangiocarcinoma cells by activating MAPK and β-catenin pathways.","date":"2023","source":"Environmental toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/37219039","citation_count":5,"is_preprint":false},{"pmid":"40634479","id":"PMC_40634479","title":"TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40634479","citation_count":5,"is_preprint":false},{"pmid":"38481282","id":"PMC_38481282","title":"TP63-TRIM29 axis regulates enhancer methylation and chromosomal instability in prostate cancer.","date":"2024","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/38481282","citation_count":5,"is_preprint":false},{"pmid":"39543168","id":"PMC_39543168","title":"microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39543168","citation_count":5,"is_preprint":false},{"pmid":"37717692","id":"PMC_37717692","title":"NAP1L5 facilitates pancreatic ductal adenocarcinoma progression via TRIM29-mediated ubiquitination of PHLPP1.","date":"2023","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/37717692","citation_count":5,"is_preprint":false},{"pmid":"37837384","id":"PMC_37837384","title":"TRIM29 promotes the progression of colorectal cancer by suppressing EZH2 degradation.","date":"2023","source":"Experimental biology and medicine (Maywood, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/37837384","citation_count":4,"is_preprint":false},{"pmid":"34485714","id":"PMC_34485714","title":"KLF4 transactivates TRIM29 expression and modulates keratin network.","date":"2021","source":"Biochemistry and biophysics reports","url":"https://pubmed.ncbi.nlm.nih.gov/34485714","citation_count":4,"is_preprint":false},{"pmid":"41219493","id":"PMC_41219493","title":"USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination.","date":"2025","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/41219493","citation_count":3,"is_preprint":false},{"pmid":"40420099","id":"PMC_40420099","title":"TRIM29 upregulation contributes to chemoresistance in triple negative breast cancer via modulating S100P-β-catenin axis.","date":"2025","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/40420099","citation_count":3,"is_preprint":false},{"pmid":"40325507","id":"PMC_40325507","title":"METTL3 promotes podocyte pyroptosis in diabetic nephropathy through N6-methyladenosine modification of TRIM29 mRNA.","date":"2025","source":"Renal failure","url":"https://pubmed.ncbi.nlm.nih.gov/40325507","citation_count":3,"is_preprint":false},{"pmid":"38393440","id":"PMC_38393440","title":"TRIM29 modulates proteins involved in PTEN/AKT/mTOR and JAK2/STAT3 signaling pathway and suppresses the progression of hepatocellular carcinoma.","date":"2024","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/38393440","citation_count":3,"is_preprint":false},{"pmid":"37218209","id":"PMC_37218209","title":"Targeting TRIM29 As a Negative Regulator of CAR-NK Cell Effector Function to Improve Antitumor Efficacy of these Cells: A Perspective.","date":"2024","source":"Current molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37218209","citation_count":3,"is_preprint":false},{"pmid":"38213743","id":"PMC_38213743","title":"Mesenchymal Stem Cells Accelerate Recovery of Acetic Acid-Induced Chronic Gastric Ulcer by Regulating Ekt/Akt/TRIM29 Axis.","date":"2024","source":"Stem cells international","url":"https://pubmed.ncbi.nlm.nih.gov/38213743","citation_count":3,"is_preprint":false},{"pmid":"40908312","id":"PMC_40908312","title":"TRIM29 promotes bladder cancer invasion by regulating the intermediate filament network and focal adhesion.","date":"2025","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/40908312","citation_count":2,"is_preprint":false},{"pmid":"32833505","id":"PMC_32833505","title":"Alteration in Expression of Trim29, TRIM37, TRIM44, and β-Catenin Genes After Irradiation in Human Cells with Different Radiosensitivity.","date":"2020","source":"Cancer biotherapy & radiopharmaceuticals","url":"https://pubmed.ncbi.nlm.nih.gov/32833505","citation_count":2,"is_preprint":false},{"pmid":"38168254","id":"PMC_38168254","title":"TRIM29 promotes bladder cancer invasion by regulating the intermediate filament network and focal adhesion.","date":"2023","source":"Research square","url":"https://pubmed.ncbi.nlm.nih.gov/38168254","citation_count":2,"is_preprint":false},{"pmid":"40389046","id":"PMC_40389046","title":"TRIM29 promotes liver metastasis via enhancing hepatic colonization by stabilizing FAM83H to regulate keratin network in colorectal cancer.","date":"2025","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/40389046","citation_count":1,"is_preprint":false},{"pmid":"37644752","id":"PMC_37644752","title":"Silencing TRIM29 Sensitizes Non-small Cell Lung Cancer Cells to Anlotinib by Promoting Apoptosis via Binding RAD50.","date":"2024","source":"Current cancer drug targets","url":"https://pubmed.ncbi.nlm.nih.gov/37644752","citation_count":1,"is_preprint":false},{"pmid":"38345749","id":"PMC_38345749","title":"O-GlcNAcylation of TRIM29 and OGT translation forms a feedback loop to promote adaptive response of PDAC cells to glucose deficiency.","date":"2024","source":"Cellular oncology (Dordrecht, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/38345749","citation_count":1,"is_preprint":false},{"pmid":"40362175","id":"PMC_40362175","title":"A Novel Rexinoid Agonist, UAB116, Decreases Metastatic Phenotype in Hepatoblastoma by Inhibiting the Wnt/β-Catenin Pathway via Upregulation of TRIM29.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40362175","citation_count":1,"is_preprint":false},{"pmid":"41601651","id":"PMC_41601651","title":"TRIM29 drives ulcerative colitis by disrupting lipid metabolism via lysosomal dysfunction: a multi-omics and experimental study.","date":"2026","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41601651","citation_count":1,"is_preprint":false},{"pmid":"41251350","id":"PMC_41251350","title":"TRIM29 inhibits PRRSV replication by targeting nsp11 for degradation.","date":"2025","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/41251350","citation_count":0,"is_preprint":false},{"pmid":"41534311","id":"PMC_41534311","title":"Expression of TRIM29 and its association with p40 and TTF1 in lung carcinoma.","date":"2026","source":"Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia","url":"https://pubmed.ncbi.nlm.nih.gov/41534311","citation_count":0,"is_preprint":false},{"pmid":"41688430","id":"PMC_41688430","title":"Lactylation-drived TRIM29 induces invasive behavior and lymph node metastasis in gastric cancer via hnRNPA1-mediated Wnt/β-catenin pathway.","date":"2026","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/41688430","citation_count":0,"is_preprint":false},{"pmid":"41770824","id":"PMC_41770824","title":"TRIM29 knockout pigs exhibit enhanced broad-spectrum disease resilience by amplifying type I interferon antiviral defenses.","date":"2026","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41770824","citation_count":0,"is_preprint":false},{"pmid":"41952208","id":"PMC_41952208","title":"TRIM29 promotes pancreatic cancer MVI via IκBα K48-ubiquitination and NF-κB activation in CXCL5⁺ epithelial cells.","date":"2026","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/41952208","citation_count":0,"is_preprint":false},{"pmid":"41963599","id":"PMC_41963599","title":"TRIM29 suppresses malignant progression in lung squamous cell carcinoma by shaping an immunosuppressive tumor microenvironment.","date":"2026","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41963599","citation_count":0,"is_preprint":false},{"pmid":"41866442","id":"PMC_41866442","title":"TRIM29 promotes epithelial-mesenchymal transition, angiogenesis, and stromal remodeling in lung adenocarcinoma: integrated validation at histologic, transcriptomic, and protein levels.","date":"2026","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41866442","citation_count":0,"is_preprint":false},{"pmid":"40341385","id":"PMC_40341385","title":"[Retracted] RNA interference against TRIM29 inhibits migration and invasion of colorectal cancer cells.","date":"2025","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/40341385","citation_count":0,"is_preprint":false},{"pmid":"42239777","id":"PMC_42239777","title":"TRIM29 is Critical for Bladder Cancer Progression and Modulates the Tumor-Immune Niche.","date":"2026","source":"Research square","url":"https://pubmed.ncbi.nlm.nih.gov/42239777","citation_count":0,"is_preprint":false},{"pmid":"41992967","id":"PMC_41992967","title":"[Corrigendum] MicroRNA‑122 acts as tumor suppressor by targeting TRIM29 and blocking the activity of PI3K/AKT signaling in nasopharyngeal carcinoma in vitro.","date":"2026","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/41992967","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":50335,"output_tokens":8224,"usd":0.137183,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":18077,"output_tokens":4926,"usd":0.106768,"stage2_stop_reason":"end_turn"},"total_usd":0.243951,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"TRIM29 induces K48-linked ubiquitination of STING (Stimulator of Interferon Genes), leading to its rapid proteasomal degradation, thereby suppressing the cytosolic dsDNA-sensing innate immune pathway and promoting DNA virus persistence.\",\n      \"method\": \"Mechanistic studies in human airway epithelial cells and Trim29-/- mice; ubiquitination assays; knockdown and knockout functional readouts (IFN production, viral titers)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal mechanistic validation in multiple cell types and in vivo mouse models, independently replicated in a second paper (PMID:29581886)\",\n      \"pmids\": [\"29038422\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TRIM29 targets STING for K48-linked ubiquitination and proteasomal degradation in macrophages and dendritic cells, negatively regulating the STING-TBK1-IRF3 signaling axis in response to DNA viruses and cytosolic dsDNA.\",\n      \"method\": \"Ubiquitination assays, TRIM29 KO mice (HSV-1 infection model), IFN measurement, Western blot for STING degradation\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — independent replication of STING K48-ubiquitination mechanism across two labs with in vivo validation\",\n      \"pmids\": [\"29581886\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TRIM29 directly binds NEMO (IKK-γ) and induces its K48-linked ubiquitination and proteasomal degradation, thereby inhibiting both IRF- and NF-κB-mediated signaling in alveolar macrophages.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, Trim29-/- mouse model (influenza and H. influenzae challenge), cytokine measurement\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding demonstrated by Co-IP, degradation confirmed biochemically, functional consequences validated in vivo\",\n      \"pmids\": [\"27695001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TRIM29 interacts with MAVS and induces its K11-linked ubiquitination and proteasomal degradation, negatively regulating type I IFN production in response to dsRNA viruses (reovirus, poly I:C).\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, Trim29-/- mouse model (reovirus challenge), IFN measurement\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding and ubiquitination demonstrated biochemically with in vivo confirmation in knockout mice\",\n      \"pmids\": [\"29769269\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ATDC/TRIM29 binds p53, sequesters it outside the nucleus, and represses p53-regulated gene expression (p21, NOXA), thereby promoting cell proliferation and resistance to ionizing radiation. This interaction is modulated by acetylation of lysine 116 on ATDC.\",\n      \"method\": \"Co-immunoprecipitation, reporter gene assays, immunofluorescence (p53 localization), RNAi silencing, cell proliferation assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding confirmed, subcellular localization shift demonstrated, functional gene expression readouts, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"20368352\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"HDAC9 co-purifies with TRIM29/ATDC and deacetylates it, thereby altering TRIM29's ability to associate with p53 and inhibiting TRIM29's cell proliferation-promoting activity.\",\n      \"method\": \"Biochemical co-purification, deacetylation assay, co-immunoprecipitation, cell proliferation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — enzymatic deacetylation demonstrated biochemically with functional validation, single lab, multiple methods\",\n      \"pmids\": [\"20947501\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"TRIM29 binds Tip60 acetyltransferase (identified by yeast two-hybrid screening), promotes Tip60 degradation and altered localization, and reduces Tip60-mediated acetylation of p53 at lysine 120, thereby suppressing apoptosis and enhancing cell growth.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, Western blot for Tip60 levels, p53-K120 acetylation assay, UV-induced apoptosis assay (HCT116 cells)\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus Co-IP binding, functional acetylation readout, single lab\",\n      \"pmids\": [\"21463657\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TRIM29 functions as a histone-binding scaffold protein that interacts with BRCA1-associated surveillance complex, cohesin, DNA-PKcs, and components of the TIP60 complex, assembling them into damaged chromatin; TRIM29 binding to modified H3 and H4 tails in nucleosomes is required for H2AX phosphorylation and cell viability after ionizing radiation.\",\n      \"method\": \"Mass spectrometry-based proteomics (MudPIT), co-immunoprecipitation, histone binding assays, chromatin fractionation, γH2AX readout, clonogenic survival after IR\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (MS interactome, Co-IP, in vitro nucleosome binding, functional IR assay) in a single rigorous study\",\n      \"pmids\": [\"26095369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ATDC/TRIM29 is directly phosphorylated by MAPKAP kinase 2 (MK2) at Serine 550 in an ATM-dependent manner, and this phosphorylation is required for ATDC's radioprotective function in pancreatic cancer cells.\",\n      \"method\": \"In vitro kinase assay (MK2 phosphorylating ATDC), site-directed mutagenesis (S550 mutants), clonogenic survival after IR, mouse xenograft model\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase assay plus mutagenesis plus functional in vivo xenograft validation, single lab\",\n      \"pmids\": [\"24469230\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ATDC/TRIM29 overexpression in vivo drives both noninvasive and invasive bladder carcinoma in transgenic mice by suppressing miR-29 expression, leading to DNMT3A upregulation, DNA methylation, and silencing of the tumor suppressor PTEN.\",\n      \"method\": \"Transgenic mouse model (ATDC overexpression), miRNA profiling, DNMT3A and PTEN expression analysis, methylation assays\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo transgenic model with downstream pathway validation, single lab with multiple methods\",\n      \"pmids\": [\"26471361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"TRIM29 suppresses invasive breast cancer behavior by inhibiting TWIST1 activity; TWIST1 transcriptionally represses TRIM29 expression by directly binding E-box elements in the TRIM29 promoter, establishing a negative regulatory feedback loop.\",\n      \"method\": \"RNAi silencing, TWIST1 overexpression/knockdown, promoter-luciferase reporter assay with E-box mutation, EMT marker analysis (E/N-cadherin, vimentin, EpCAM)\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase reporter with direct binding evidence, functional EMT phenotype readouts, single lab\",\n      \"pmids\": [\"24950909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TRIM29 ubiquitinates and degrades TAB2 (TGF-β-activated kinase 1 binding protein 2) in NK cells following activation, thereby negatively regulating IFN-γ production; TRIM29-deficient NK cells produce more IFN-γ and protect mice from murine CMV infection.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, TRIM29-specific NK cell knockout mice (CMV challenge), IFN-γ measurement\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding and ubiquitination demonstrated, in vivo NK-specific knockout validation with clear functional phenotype\",\n      \"pmids\": [\"31270148\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Loss of TRIM29 in squamous cell carcinoma cells leads to ectopic keratin localization; TRIM29 interacts with keratins and keratin-interacting protein FAM83H to regulate the keratin distribution network.\",\n      \"method\": \"Comprehensive proteomics, co-immunoprecipitation, immunofluorescence (keratin localization), TRIM29 knockdown/overexpression migration/invasion assays\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry interactome plus Co-IP binding, direct localization readout, functional migration assays, single lab\",\n      \"pmids\": [\"30389700\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TRIM29 interacts with IGF2BP1 and induces its K48-linked ubiquitination at Lys440 and Lys450, leading to IGF2BP1 degradation; loss of IGF2BP1 reduces PD-L1 mRNA stability, enhancing anti-tumor T-cell immunity in gastric cancer.\",\n      \"method\": \"Proteomics, co-immunoprecipitation, in vitro ubiquitination assay (specific lysine sites), PD-L1 3'UTR reporter assay, in vivo tumor model\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — site-specific ubiquitination demonstrated biochemically with multiple downstream functional readouts, single lab\",\n      \"pmids\": [\"38029830\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TRIM29 interacts with PERK (protein kinase RNA-like ER kinase) and promotes SUMOylation of PERK to maintain its stability, thereby sustaining PERK-mediated ER stress, apoptosis, and ROS responses that promote viral replication in cardiomyocytes during viral myocarditis.\",\n      \"method\": \"Co-immunoprecipitation, SUMOylation assay, TRIM29-/- mouse model (cardiotropic virus challenge), PERK inhibitor (GSK2656157) in vivo treatment, cardiac function readouts\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and SUMOylation demonstrated, pharmacological and genetic validation in vivo, single lab with multiple methods\",\n      \"pmids\": [\"38664417\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TRIM29 promotes K48-linked ubiquitination and degradation of both NLRP6 and NLRP9b in intestinal epithelial cells, suppressing IFN-λ and IL-18 production during enteric RNA virus infection, thereby facilitating viral-induced intestinal inflammation.\",\n      \"method\": \"TRIM29 knockout in intestinal epithelial cells (rotavirus and EMCV models), ubiquitination assay, cytokine measurement (IFN-λ, IL-18), immune cell recruitment analysis\",\n      \"journal\": \"Mucosal immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — K48-ubiquitination of two substrates demonstrated with IEC-specific KO and in vivo viral challenge models\",\n      \"pmids\": [\"39396665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TRIM29 knockdown in pancreatic cancer cells destabilizes ISG15 protein by promoting its processing via calpain 3 (CAPN3); TRIM29 normally protects ISG15 from CAPN3-mediated cleavage, and extracellular free ISG15 (secreted) maintains cancer stem cell-like features via autocrine signaling.\",\n      \"method\": \"TRIM29 knockdown, CAPN3 inhibitor treatment, ISG15 stability assays, stem cell sphere formation, rescue experiments with secreted ISG15\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ISG15 stabilization mechanism biochemically characterized, single lab, multiple functional assays\",\n      \"pmids\": [\"31501523\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TRIM29 directly binds YAP1 and reduces its K48-linked ubiquitination and degradation, thereby stabilizing YAP1 and promoting pancreatic cancer cell proliferation.\",\n      \"method\": \"Co-immunoprecipitation, in vitro ubiquitination assay, YAP1 protein stability analysis, rescue proliferation experiments, mouse xenograft\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and reduced ubiquitination shown biochemically with in vivo validation, single lab\",\n      \"pmids\": [\"34353343\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TRIM29 promotes degradation of pyruvate kinase M1 (PKM1) via the ubiquitin-proteasome pathway by directly targeting PKM1, reducing the PKM1/PKM2 ratio and promoting PKM2-mediated aerobic glycolysis (Warburg effect) in colorectal cancer.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, PKM1/PKM2 ratio analysis, metabolic assays, TRIM29 knockdown/overexpression in vitro and in vivo\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct ubiquitination target identified biochemically with functional metabolic readout, single lab\",\n      \"pmids\": [\"33495406\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TRIM29 interacts with IκBα and mediates its K48-linked ubiquitination-dependent degradation, leading to NF-κB activation and downstream NLRP3 inflammasome-mediated podocyte pyroptosis in diabetic nephropathy.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, TRIM29 overexpression/knockdown with NF-κB inhibitor rescue, NLRP3/caspase-1/GSDMD-N Western blot, flow cytometry for pyroptosis\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and ubiquitination of IκBα demonstrated, functional pathway rescue, single lab\",\n      \"pmids\": [\"36841942\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TRIM29 interacts with NLRC4 inflammasome protein and promotes its K48-linked polyubiquitination and proteasomal degradation in neurons and microglia, thereby reducing NLRC4 inflammasome activation and limiting neuronal injury in ischemic stroke.\",\n      \"method\": \"Co-immunoprecipitation with truncation mutants, ubiquitination assay, TRIM29 knockout mice (MCAO model), immunofluorescence for apoptosis/pyroptosis, cytokine measurement\",\n      \"journal\": \"Stroke\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain-mapping Co-IP plus ubiquitination assay with in vivo KO model, single lab\",\n      \"pmids\": [\"37021569\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"TRIM29 is required for regulation of the p63 (TAp63α)-mediated pathway in cervical cancer cells; TRIM29 controls TAp63α expression levels and modulates integrin expression and ZEB1 to regulate cell adhesion and invasion.\",\n      \"method\": \"TRIM29 knockdown and overexpression, TAp63α expression analysis, integrin profiling, cell adhesion and invasion assays\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — functional phenotype with gene expression readouts but no direct binding or ubiquitination assay shown for p63, single lab\",\n      \"pmids\": [\"26071105\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TRIM29 is required for efficient recruitment of 53BP1 to DNA double-strand break sites; TRIM29 knockout cells show impaired 53BP1 foci formation after etoposide, reduced NHEJ efficiency, and compensatory upregulation of RAD51-mediated homologous recombination.\",\n      \"method\": \"Gene targeting (homologous recombination) in DT40 cells, clonogenic survival assays, immunofluorescence for γH2AX, 53BP1, and RAD51 foci\",\n      \"journal\": \"FEBS open bio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with defined DSB repair pathway readouts, multiple repair markers assessed\",\n      \"pmids\": [\"33017104\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"USP18 interacts with TRIM29 and facilitates its K27-linked ubiquitination by recruiting TRIM21 (which directly ubiquitinates TRIM29 at Lys561); this promotes TRIM29 oligomerization and nuclear translocation, enhancing DNA damage response and radioresistance in nasopharyngeal carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay (site-specific K561 mutant), immunofluorescence for nuclear translocation, radiosensitivity assays\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — site-specific ubiquitination mapped, nuclear translocation shown, functional radioresistance readout, single lab\",\n      \"pmids\": [\"41219493\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TRIM29 interacts with VDAC1 to activate mitophagy, which clears damaged mitochondria and reduces ROS accumulation, thereby preventing cellular senescence in nasopharyngeal carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, TRIM29 silencing with ROS measurement, mitophagy assays, cellular senescence assays, in vivo tumor growth\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding demonstrated, mechanistic link to mitophagy and ROS established, single lab\",\n      \"pmids\": [\"37248790\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TRIM29 promotes K48-linked ubiquitination and proteasomal degradation of PRRSV nsp11 (binding via TRIM29's coiled-coil domain at conserved catalytic residue K173), thereby inhibiting nsp11's suppression of IFN-β and restricting PRRSV replication.\",\n      \"method\": \"Co-immunoprecipitation, in vitro ubiquitination assay (K173R mutant), domain-mapping experiments, IFN-β reporter assays, viral replication assays\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct binding domain mapped, site-specific ubiquitination demonstrated, functional IFN and viral replication readouts, single lab\",\n      \"pmids\": [\"41251350\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TRIM29 physically interacts with K14+ intermediate filaments in bladder cancer cells, and this interaction regulates focal adhesion stability (requiring ZYX) to drive cancer cell migration and invasion.\",\n      \"method\": \"Co-immunoprecipitation, KD/KO functional assays (migration, invasion), focal adhesion analysis, K14 and ZYX knockdown rescue experiments\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein interaction demonstrated, epistasis with K14/ZYX established, single lab\",\n      \"pmids\": [\"40908312\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"O-GlcNAcylation of TRIM29 at threonine 120 (T120) is required for TRIM29-mediated adaptive responses of pancreatic cancer cells to glucose deficiency; TRIM29 and OGT form a feedback loop where OGT O-GlcNAcylates TRIM29, and TRIM29 promotes OGT translation.\",\n      \"method\": \"Western blot, mass spectrometry, WGA-immunoprecipitation, T120 site mutagenesis, protein stability and translation assays under glucose deprivation, crystal violet/flow cytometry functional assays\",\n      \"journal\": \"Cellular oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — site-specific PTM mapped by MS and mutagenesis, feedback mechanism demonstrated biochemically, single lab\",\n      \"pmids\": [\"38345749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TRIM29 degrades YBX1 through K48-linked ubiquitination, thereby inhibiting the PI3K/AKT signaling pathway and reversing lenvatinib resistance in hepatocellular carcinoma.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, transcriptome sequencing, ubiquitination assay, colony formation/CCK8/flow cytometry, in vivo xenograft\",\n      \"journal\": \"Translational oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and ubiquitination demonstrated with in vivo validation, single lab\",\n      \"pmids\": [\"39874728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TRIM29 expression in breast tumor and non-tumorigenic mammary cells is negatively regulated by ATM: basal TRIM29 levels depend on NF-κB (RelA subunit) activity, and hypoxia-induced TRIM29 upregulation requires both ATM and HIF1α through increased TRIM29 gene transcription.\",\n      \"method\": \"ATM knockdown, RelA knockdown, HIF1α inhibition, hypoxia treatment, TRIM29 promoter-reporter assays, Western blot\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis established through genetic knockdowns, transcriptional mechanism confirmed, single lab\",\n      \"pmids\": [\"27535224\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TRIM29 maintains cancer stem cell-like features in ovarian cancer by facilitating SETBP1 transcriptional activation through the VEZF1 transcription factor; TRIM29 promotes VEZF1 mRNA translation by recruiting RNA-binding protein BICC1 to the VEZF1 3'UTR, and the SETBP1/SET/PP2A axis downstream mediates the CSC phenotype.\",\n      \"method\": \"Global proteomics, co-immunoprecipitation, RNA-immunoprecipitation (RIP), luciferase reporter, TRIM29 KD rescue experiments\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomics-driven pathway with biochemical validation of BICC1/VEZF1/SETBP1 interactions, single lab\",\n      \"pmids\": [\"34973391\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TRIM29 interacts with FAM83H, stabilizes it by reducing its ubiquitination and degradation, thereby redistributing cellular keratins, activating NF-κB, upregulating PLXNB2, and enhancing CRC cell adhesion and liver metastatic colonization.\",\n      \"method\": \"Multi-omics, co-immunoprecipitation, ubiquitination assay, FAM83H stability analysis, NF-κB and PLXNB2 pathway readouts, in vivo metastasis model\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and de-ubiquitination (stabilization) mechanism demonstrated with downstream pathway validation in vivo, single lab\",\n      \"pmids\": [\"40389046\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"tRF-AspGTC binds galectin-3 and inhibits TRIM29-mediated ubiquitination of galectin-3, thereby stabilizing galectin-3, which activates TLR4/MyD88/NF-κB signaling to drive vascular smooth muscle cell phenotypic switching and intracranial aneurysm formation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, tRF-AspGTC gain/loss of function, galectin-3 stability assays, TLR4/NF-κB pathway readouts\",\n      \"journal\": \"Research (Washington, D.C.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TRIM29-mediated ubiquitination substrate identified with functional modulation demonstrated, single lab\",\n      \"pmids\": [\"39776588\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KLF4 binds a specific site in the TRIM29 promoter to transactivate its transcription, and KLF4-driven TRIM29 expression mediates KLF4-induced cell migration and modulation of the keratin network (keratin 8 phosphorylation at aa 432).\",\n      \"method\": \"Promoter-luciferase assay, ChIP or promoter binding assay, TRIM29 knockdown rescue of KLF4-induced migration, Western blot for KRT8 phosphorylation\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — promoter transactivation shown but binding assay details limited in abstract, single lab\",\n      \"pmids\": [\"34485714\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TRIM29 promotes PHLPP1 K48-linked ubiquitination and degradation in pancreatic ductal adenocarcinoma; TRIM29 is recruited by NAP1L5 which binds PHLPP1, and the resulting PHLPP1 degradation activates AKT/mTOR signaling.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assay, PHLPP1 stability analysis, NAP1L5/TRIM29 knockdown, AKT/mTOR pathway readouts\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TRIM29 as ubiquitin ligase for PHLPP1 biochemically demonstrated, single lab with multiple methods\",\n      \"pmids\": [\"37717692\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TRIM29 directly binds IκBα via its BB2 domain and catalyzes K48-linked ubiquitination and proteasomal degradation of IκBα, activating NF-κB signaling and promoting EMT in CXCL5+ pancreatic cancer cells to drive microvascular invasion.\",\n      \"method\": \"Co-immunoprecipitation (domain mapping), ubiquitination assay, ChIP-qPCR, migration/invasion assays, xenograft model\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain-mapped binding and site-specific ubiquitination demonstrated biochemically with in vivo validation, single lab\",\n      \"pmids\": [\"41952208\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TRIM29 is a RING-less E3 ubiquitin ligase (using its B-box domain) that acts as an inducible negative regulator of innate immunity by targeting key immune adaptors—STING, NEMO, MAVS, NLRP6, NLRP9b, TAB2, and NLRC4—for K48-linked polyubiquitination and proteasomal degradation; in cancer, TRIM29 also scaffolds DNA repair complexes at chromatin, sequesters p53 from the nucleus (regulated by HDAC9-mediated deacetylation and MK2/ATM-mediated phosphorylation at Ser550), suppresses Tip60-mediated p53-K120 acetylation, stabilizes oncoproteins (YAP1, EZH2, FAM83H, ISG15) by reducing their ubiquitination, and regulates keratin network distribution by binding K14/K5 intermediate filaments and FAM83H to control cell migration and invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TRIM29 is a B-box-dependent E3 ubiquitin ligase that functions as an inducible negative regulator of innate antiviral immunity and, separately, as a chromatin-associated scaffold and oncogenic stabilizer/destabilizer of cellular substrates. In immune cells, TRIM29 directly binds and ubiquitinates core signaling adaptors to terminate interferon and inflammatory responses: it drives K48-linked ubiquitination and proteasomal degradation of STING to shut down cytosolic dsDNA sensing [#0, #1], NEMO to block both IRF and NF-\\u03baB output [#2], MAVS via K11-linked chains to suppress RNA-virus-induced type I IFN [#3], TAB2 in NK cells to limit IFN-\\u03b3 [#11], and NLRP6/NLRP9b in intestinal epithelium to dampen IFN-\\u03bb and IL-18 [#15]; loss of TRIM29 in these settings enhances antiviral and inflammasome responses [#1, #15, #20]. In the DNA damage response, TRIM29 acts as a histone-binding scaffold that assembles BRCA1-associated surveillance, cohesin, DNA-PKcs and TIP60 complexes onto damaged chromatin, supporting H2AX phosphorylation and clonogenic survival after ionizing radiation [#7], and is required for 53BP1 recruitment and efficient NHEJ [#22]. Its radioprotective scaffolding activity is licensed by MK2/ATM-dependent phosphorylation at Ser550 [#8] and by USP18/TRIM21-mediated K27-linked ubiquitination at Lys561 that triggers oligomerization and nuclear translocation [#23]. TRIM29 also restrains the p53 axis\\u2014sequestering p53 outside the nucleus to repress p21/NOXA [#4] and degrading the acetyltransferase Tip60 to reduce p53-K120 acetylation and apoptosis [#6]\\u2014with HDAC9 deacetylation modulating its p53 association [#5]. Across cancers TRIM29 selectively controls substrate stability, degrading tumor-suppressive or restraining factors such as I\\u03baB\\u03b1 to activate NF-\\u03baB-driven EMT [#35, #19], PHLPP1 to activate AKT/mTOR [#34], IGF2BP1, YBX1 and PKM1 [#13, #28, #18], while stabilizing oncogenic clients including YAP1, FAM83H and ISG15 by limiting their ubiquitination [#17, #31, #16]. Through binding K14 intermediate filaments and FAM83H it reorganizes the keratin network and focal adhesions to promote migration and invasion [#12, #26, #31].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Established the first mechanistic role for TRIM29 in cancer: how it could promote proliferation and radioresistance by neutralizing p53, and how that activity is regulated by acetylation.\",\n      \"evidence\": \"Co-IP, p53 localization imaging and reporter assays plus HDAC9 deacetylation assay in cancer cells\",\n      \"pmids\": [\"20368352\", \"20947501\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of cytoplasmic p53 retention not structurally defined\", \"Whether TRIM29 ubiquitinates p53 directly not addressed\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Extended p53 regulation by showing TRIM29 degrades the Tip60 acetyltransferase, linking TRIM29 to suppression of p53-K120 acetylation and apoptosis.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, and p53-K120 acetylation/apoptosis readouts in HCT116 cells\",\n      \"pmids\": [\"21463657\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct ubiquitination of Tip60 by TRIM29 not biochemically isolated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined the upstream signals and downstream oncogenic outputs of TRIM29: MK2/ATM phosphorylation at Ser550 enables radioprotection, while overexpression drives bladder carcinoma via miR-29/DNMT3A/PTEN silencing and restrains breast cancer through a TWIST1 feedback loop.\",\n      \"evidence\": \"In vitro kinase assay with S550 mutagenesis, transgenic mouse tumor models, and promoter-reporter/EMT assays\",\n      \"pmids\": [\"24469230\", \"26471361\", \"24950909\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Context-dependent oncogenic vs tumor-suppressive roles not reconciled\", \"How S550 phosphorylation alters substrate engagement unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Reframed TRIM29 as a histone-binding chromatin scaffold, explaining its radioprotection mechanistically by showing it assembles DNA repair complexes onto damaged nucleosomes to enable H2AX phosphorylation.\",\n      \"evidence\": \"MudPIT interactome, in vitro nucleosome/histone binding, chromatin fractionation, and clonogenic IR survival\",\n      \"pmids\": [\"26095369\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Histone-mark specificity not fully mapped\", \"Relationship of scaffolding to its E3 ligase activity unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified TRIM29 as a NEMO-degrading immune brake and clarified its own transcriptional control by ATM/NF-\\u03baB/HIF1\\u03b1, establishing the negative-regulator-of-innate-immunity paradigm and its inducibility.\",\n      \"evidence\": \"Co-IP, ubiquitination assay, Trim29-/- influenza/H. influenzae challenge; ATM/RelA/HIF1\\u03b1 knockdown with promoter reporters\",\n      \"pmids\": [\"27695001\", \"27535224\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether immune and DNA-repair functions are mutually exclusive in a given cell not addressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Generalized TRIM29 as an adaptor-degrading immune suppressor across sensing pathways by demonstrating K48-ubiquitination of STING and K11-ubiquitination of MAVS, controlling DNA- and RNA-virus responses.\",\n      \"evidence\": \"Ubiquitination assays and Trim29-/- mouse infection models (HSV-1, reovirus) with IFN readouts\",\n      \"pmids\": [\"29581886\", \"29769269\", \"29038422\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Determinants of K48 vs K11 chain choice not defined\", \"B-box catalytic mechanism not structurally resolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Broadened TRIM29 immune and oncogenic substrate scope: TAB2 degradation in NK cells limits IFN-\\u03b3, IGF2BP1 degradation enhances anti-tumor immunity via PD-L1 mRNA, and TRIM29 protects ISG15 from CAPN3 cleavage to sustain stemness.\",\n      \"evidence\": \"NK-specific KO CMV model, site-specific ubiquitination assays, and ISG15 stability/sphere assays\",\n      \"pmids\": [\"31270148\", \"38029830\", \"31501523\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How TRIM29 switches between degrading and stabilizing substrates unknown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated TRIM29 substrate stabilization as an oncogenic mechanism (YAP1) and metabolic rewiring (PKM1 degradation shifting toward PKM2/Warburg), alongside RNA-level CSC control via VEZF1/BICC1.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, metabolic and proliferation assays, RIP and xenografts\",\n      \"pmids\": [\"34353343\", \"33495406\", \"34973391\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single labs per substrate\", \"Direct vs indirect ubiquitination not always distinguished\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Connected TRIM29's E3 activity to NF-\\u03baB and inflammasome control in disease contexts: I\\u03baB\\u03b1 degradation drives podocyte pyroptosis, NLRC4 degradation limits stroke injury, while VDAC1-driven mitophagy suppresses senescence.\",\n      \"evidence\": \"Co-IP/domain mapping, ubiquitination assays, KO mouse models (MCAO), and mitophagy/ROS assays\",\n      \"pmids\": [\"36841942\", \"37021569\", \"37248790\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Opposing NF-\\u03baB effects (activation via I\\u03baB\\u03b1 vs suppression via NEMO) context-dependence unresolved\", \"Single labs\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed additional regulatory layers and substrates: O-GlcNAcylation at T120 and an OGT feedback loop support glucose-stress adaptation, PERK SUMOylation sustains ER stress in myocarditis, PHLPP1 degradation activates AKT/mTOR, and NLRP6/NLRP9b degradation shapes intestinal antiviral immunity.\",\n      \"evidence\": \"MS-mapped PTM site mutagenesis, SUMOylation/ubiquitination assays, and KO mouse viral/metabolic models\",\n      \"pmids\": [\"38345749\", \"38664417\", \"37717692\", \"39396665\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Hierarchy of PTMs governing TRIM29 activity not integrated\", \"Tissue-specific substrate selection unexplained\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Mapped TRIM29 activation and effector mechanisms: USP18/TRIM21 K27-ubiquitination at K561 drives nuclear translocation/radioresistance, BB2-domain-dependent I\\u03baB\\u03b1 degradation drives pancreatic EMT, coiled-coil targeting of PRRSV nsp11 restricts virus, and K14/ZYX-coupled focal adhesion control plus FAM83H stabilization drive invasion/metastasis.\",\n      \"evidence\": \"Domain-mapping Co-IP, site-specific ubiquitination assays, nuclear translocation imaging, and in vivo invasion/metastasis models\",\n      \"pmids\": [\"41219493\", \"41952208\", \"41251350\", \"40908312\", \"40389046\", \"39874728\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of B-box/coiled-coil substrate recognition still lacking\", \"Single labs per substrate\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TRIM29 selects between K48, K11, and K27 chain types and between degradative versus stabilizing outcomes for its many substrates, and how its immune-suppressive and DNA-repair scaffolding functions are coordinated within a cell, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the B-box catalytic mechanism\", \"No unifying rule for substrate fate (degrade vs stabilize)\", \"Cross-talk between immune and chromatin roles uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 1, 2, 3, 11, 13, 15, 20, 35]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 2, 3, 13, 15, 20, 34, 35]},\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [0, 2, 13, 35]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [7, 12, 26]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [12, 26]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [16, 17, 31]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [4, 23]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [7, 22]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [4, 12]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [12, 26]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 1, 2, 3, 11, 15]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [7, 22]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 2, 13, 17, 34, 35]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [19, 34, 35]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [9, 19, 32]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [18, 27]}\n    ],\n    \"complexes\": [\"TIP60 complex\", \"BRCA1-associated surveillance complex\"],\n    \"partners\": [\"STING1\", \"NEMO\", \"MAVS\", \"TAB2\", \"FAM83H\", \"YAP1\", \"IGF2BP1\", \"PERK\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":6,"faith_total":6,"faith_pct":100.0}}