Affinage

TRIM16

Tripartite motif-containing protein 16 · UniProt O95361

Length
564 aa
Mass
64.0 kDa
Annotated
2026-06-13
68 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM16 is an atypical E3 ubiquitin ligase that functions as a versatile scaffold coordinating proteostasis, selective autophagy, oxidative stress responses, and innate immunity (PMID:22629402, PMID:30143514). It lacks a classical RING domain but its B-box domains adopt RING-like folds that confer auto-polyubiquitination activity; it homodimerizes through its coiled-coil domain and heterodimerizes with other TRIM proteins (TRIM24, PML, MID1) (PMID:22629402). As a ubiquitin ligase TRIM16 catalyzes linkage-specific ubiquitination with distinct outcomes: K48-linked chains target substrates for proteasomal degradation while K63-linked chains stabilize or relocalize partners. Through K48-linked ubiquitination it degrades the mesenchymal protein vimentin (PMID:33046716), the EMT repressor Snail (PMID:34265287, PMID:40991993), NLRP3 (PMID:36208489), NFKBIZ (PMID:38581570), phospho-TAK1 (PMID:38154547), and the antiviral sensor RIG-I at K258 (PMID:42171628); through K63-linked ubiquitination it stabilizes and activates NRF2 to drive antioxidant gene expression (PMID:30143514, PMID:36851605) and modifies YAP1, FGF7, and the endocytic adaptor DAB2 (at K656 via its SPRY domain) to control nuclear signaling and integrin trafficking (PMID:41437125, PMID:40796898, PMID:40575853). A central role is in selective autophagy: TRIM16 assembles core autophagic machinery (p62, ULK1, ATG16L1, LC3B) on ubiquitinated substrates to drive aggrephagy (PMID:30143514), cooperates with Galectin-3 to sense lysosomal membrane permeabilization and initiate lysophagy (PMID:27728777, PMID:37357416, PMID:34135057), and mediates secretory autophagy by trafficking LC3B-positive vesicles to the plasma membrane for cytokine release (PMID:40383937). TRIM16 also acts in the nucleus, binding and downregulating E2F1 to restrain proliferation and binding the IFNβ1 promoter to regulate innate immune transcription (PMID:20729920, PMID:22009481, PMID:25333256). Across cancer models, loss of TRIM16 promotes invasion and metastasis (PMID:33046716, PMID:34265287).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 Medium

    Established the first functional handle on TRIM16 (EBBP) by defining its cytoplasmic localization and hormone-responsive expression, raising the question of what cellular role this estrogen-induced protein played.

    Evidence Northern blot, immunofluorescence, and ER-mutant transfection in mammary epithelial cells

    PMID:9817599

    Open questions at the time
    • No molecular activity assigned
    • Mechanism of estrogen induction not resolved beyond ER dependence
  2. 2010 High

    Resolved how TRIM16 suppresses tumor cell behavior by showing it directly binds and downregulates both cytoplasmic vimentin and nuclear E2F1, coupling reduced motility to inhibited replication.

    Evidence Reciprocal Co-IP, knockdown/overexpression, subcellular fractionation, and xenograft in neuroblastoma

    PMID:20729920

    Open questions at the time
    • Mechanism of vimentin and E2F1 downregulation (degradation vs. sequestration) not defined
    • Signal triggering retinoid-induced nuclear translocation unknown
  3. 2011 High

    Confirmed the E2F1/vimentin tumor-suppressive axis in a second cancer context and mapped the C-terminal RFP-like domain as required for reduced migration, linking domain architecture to function.

    Evidence Domain-mapping deletion mutants, Co-IP, siRNA, migration assay in squamous cell carcinoma

    PMID:22009481

    Open questions at the time
    • Catalytic basis of substrate downregulation not yet established
    • Connection between nuclear translocation and differentiation unresolved
  4. 2012 High

    Defined TRIM16 as an atypical E3 ligase, answering how a RING-less TRIM protein achieves catalytic activity: its B-box domains adopt RING-like folds and support auto-ubiquitination, and it dimerizes via its coiled-coil.

    Evidence Structural modelling, in vitro and in vivo ubiquitination assays, Co-IP, deletion mutants

    PMID:22629402

    Open questions at the time
    • Physiological substrates not yet identified
    • Chain-linkage specificity not characterized
  5. 2018 High

    Integrated TRIM16 into oxidative-stress and autophagy biology by showing it joins the p62-KEAP1-NRF2 complex, stabilizes NRF2 via K63 ubiquitination, and scaffolds core autophagy factors to clear protein aggregates.

    Evidence Co-IP, K63-ubiquitination assay, in vitro and in vivo functional studies, immunofluorescence

    PMID:30143514

    Open questions at the time
    • Direct E2 partner for K63 chains not identified
    • How substrate recognition is partitioned between aggrephagy and proteasomal targeting unclear
  6. 2019 Medium

    Extended the autophagy role to membrane-damage surveillance and tissue differentiation, showing TRIM16-Galectin-3-ULK1 recruitment initiates lysophagy at damaged endomembranes and stabilizes ULK1/Beclin1 to drive osteogenesis.

    Evidence Co-IP, autophagy flux assays, shRNA/overexpression in cells and hBMSCs (refs 27728777, 31521826)

    PMID:27728777 PMID:31521826

    Open questions at the time
    • Whether ULK1/Beclin1 stabilization is ubiquitin-dependent not resolved
    • Stoichiometry of TRIM16-Galectin-3 recruitment unknown
  7. 2020 High

    Provided the first direct K48-ubiquitination substrate proof for TRIM16, showing it degrades vimentin and that a competing lncRNA (VAL) blocks this to promote metastasis, mechanistically explaining TRIM16 loss in invasion.

    Evidence Co-IP, K48-ubiquitination assay, rescue experiments, in vivo metastasis model

    PMID:33046716

    Open questions at the time
    • Ubiquitination site on vimentin not mapped
    • Generality of lncRNA competition across substrates unknown
  8. 2022 High

    Expanded TRIM16's substrate repertoire and revealed ligase-independent scaffolding, degrading Src, NLRP3, and competing with TRAF3 at NIK, positioning TRIM16 in cardiac protection, inflammasome control, and NF-κB-driven cancer metabolism.

    Evidence Co-IP, ubiquitination assays, cardiac KO/AAV9 and xenograft models, domain competition analysis

    PMID:35437018 PMID:36208489 PMID:36504902

    Open questions at the time
    • Determinants selecting ligase-dependent vs. scaffold-only modes unknown
    • Whether cardiac and cancer phenotypes share a common substrate-recognition logic unresolved
  9. 2023 Medium

    Consolidated TRIM16 as a multi-pathway redox and degradation hub, degrading phospho-TAK1 while elevating YAP1/Nrf2, driving Galectin-3-dependent lysophagy of amyloid-laden lysosomes, and stabilizing NRF2 during viral infection.

    Evidence Co-IP, K48/K63-ubiquitination assays, AAV9 cardiac models, iPSC-derived neurons, viral infection systems

    PMID:36851605 PMID:37357416 PMID:38154547

    Open questions at the time
    • Direct vs. indirect routing of YAP1 nuclear translocation not separated from Nrf2 effects
    • In vivo relevance of neuronal lysophagy to amyloid pathology not established
  10. 2025 High

    Defined site-specific and linkage-specific substrate logic and added secretory autophagy, mapping K63 ubiquitination of DAB2 at K656 via the SPRY domain, K48 ubiquitination of Snail at K146, and LC3B-vesicle trafficking to the plasma membrane for IL6 secretion.

    Evidence IP-MS, site-directed mutagenesis, SPRY deletion, tissue-specific KO mice, TEM and live imaging, PLA

    PMID:39367988 PMID:40383937 PMID:40575853 PMID:40990506 PMID:40991993 PMID:41134044 PMID:41437125

    Open questions at the time
    • Structural basis distinguishing K48 vs. K63 vs. K27 chain output unresolved
    • How a single SPRY/B-box scaffold selects such diverse substrates not explained
  11. 2026 High

    Positioned TRIM16 at the antiviral innate-immune and ferroptosis interface, showing K48 degradation of RIG-I at K258 (scaffolded by FGF8) and K27 degradation of SARS-CoV-2 ORF3a, plus KEAP1/TFR1 autophagic degradation limiting iron-driven lipid peroxidation.

    Evidence TurboID, Co-IP, K48/K27-ubiquitination assays, site-directed mutagenesis, viral replication assays, multi-omics

    PMID:42092406 PMID:42107085 PMID:42171628

    Open questions at the time
    • Whether TRIM16 net promotes or restrains antiviral immunity across viruses is context-dependent and unreconciled
    • Endogenous regulators governing TRIM16 antiviral activity in vivo unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIM16's RING-less B-box catalytic core, coiled-coil dimerization, and SPRY substrate domain together encode the choice among K48, K63, and K27 chain linkages and among proteasomal, autophagic, scaffold, and trafficking outcomes remains unresolved.
  • No high-resolution structure of the catalytic/substrate interface
  • E2 partners directing each chain linkage not identified
  • Rules selecting degradation vs. scaffolding vs. autophagic routing undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005764 lysosome 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-9612973 Autophagy 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1640170 Cell Cycle 3
Partners
DAB2E2F1KEAP1LC3BLGALS3NRF2SQSTM1ULK1
Complex memberships
p62-KEAP1-NRF2 complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 TRIM16 lacks a classical RING domain but its B-box domains adopt RING-like folds; it possesses auto-polyubiquitination activity and acts as an E3 ubiquitin ligase both in vivo and in vitro. TRIM16 homodimerizes through its coiled-coil domain and heterodimerizes with TRIM24, PML, and MID1. 3D structural modelling, in vitro and in vivo ubiquitination assays, co-immunoprecipitation, deletion mutant analysis PloS one High 22629402
2010 TRIM16 directly binds cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells; TRIM16 reduces cell motility through vimentin downregulation and inhibits cell replication by binding and downregulating nuclear E2F1. Retinoid treatment causes TRIM16 to translocate to the nucleus. Co-immunoprecipitation, overexpression, knockdown, subcellular fractionation, live imaging, in vivo xenograft Oncogene High 20729920
2009 TRIM16 (EBBP) increases histone acetylation and de-represses RARβ2 and CYP26A1 transcription via the retinoic acid response element (βRARE); it inhibits cell growth through effects on cyclin D1 and phospho-Rb in retinoid-resistant cancer cells. Overexpression, chromatin modification assays, reporter assays, Western blot for cyclin D1/Rb Cancer letters Medium 19147277
1998 TRIM16 (EBBP) is predominantly cytoplasmically localized; its mRNA is induced by estrogen and 4-hydroxy-tamoxifen through an ER-mediated, cycloheximide-insensitive mechanism in mammary epithelial cells expressing an ER transgene. Northern blot, immunofluorescence/subcellular localization, estrogen receptor mutant transfection studies Molecular endocrinology Medium 9817599
2011 In squamous cell carcinoma cells, TRIM16 binds and downregulates nuclear E2F1, required for cell replication, and directly binds and downregulates vimentin to reduce cell migration. The C-terminal RFP-like domain of TRIM16 is required for reduced cell migration. Overexpressed TRIM16 translocates to the nucleus, inducing growth arrest and differentiation. Co-immunoprecipitation, TRIM16 deletion mutants, overexpression, siRNA knockdown, migration assay The Journal of pathology High 22009481
2013 TRIM16 nuclear localization is cell-cycle dependent, increasing and shifting to the nucleus during G1 phase; a specific uncharacterized protein domain of TRIM16 is required for both its nuclear localization and growth inhibitory effects. TRIM16 regulates cell cycle progression through changes in Cyclin D1 and p27 expression. Immunohistochemistry in TH-MYCN mouse model, TRIM16 deletion mutants, flow cytometry, Western blot for Cyclin D1/p27 Cell cycle Medium 23422002
2013 TRIM16 overexpression induces apoptosis in cancer cells by directly interacting with caspase-2 and inducing caspase-2 activity; caspase-2 activity is required for TRIM16-initiated apoptosis. TRIM16 increases procaspase-2 protein levels. Co-immunoprecipitation, co-localization, caspase activity assay, caspase-2 knockdown rescue experiment Apoptosis Medium 23404198
2014 TRIM16 directly binds the IFNβ1 gene promoter (shown by ChIP) and reduces melanoma cell migration and proliferation in an IFNβ1-dependent manner. TRIM16 protein stability is reduced in melanoma cells through DNA methylation and reduced protein stability. Chromatin immunoprecipitation (ChIP), overexpression, siRNA knockdown, migration/proliferation assays Oncotarget Medium 25333256
2018 TRIM16 is an integral part of the p62-KEAP1-NRF2 complex and stabilizes NRF2 through multiple mechanisms including K63-linked ubiquitination of NRF2. TRIM16 activates NRF2 target genes including p62 and ubiquitin pathway genes, leading to ubiquitination of misfolded proteins and aggregate formation. TRIM16 acts as a scaffold protein interacting with p62, ULK1, ATG16L1, and LC3B to facilitate autophagic degradation of protein aggregates. Co-immunoprecipitation, ubiquitination assay, in vivo and in vitro functional studies, siRNA knockdown, Western blot, immunofluorescence The EMBO journal High 30143514
2016 TRIM16 interacts with Galectin-3 to orchestrate recruitment of core autophagic factors and activates selective autophagy (lysophagy) at damaged endomembranes. Co-immunoprecipitation, autophagy functional assays (referenced from Chauhan et al. 2016) Developmental cell Medium 27728777
2019 TRIM16 interacts with Galectin-3 through ULK1; osteogenic induction enhances the association between TRIM16 and ULK1 or Beclin1, and TRIM16 increases the stability of ULK1 and Beclin1 to promote osteogenic differentiation of hBMSCs via autophagy. Co-immunoprecipitation, shRNA knockdown, overexpression, autophagy flux assays, alkaline phosphatase/Alizarin Red staining Bone Medium 31521826
2020 TRIM16 directly promotes K48-linked polyubiquitination and degradation of vimentin; a lncRNA (VAL) competitively abrogates this TRIM16-dependent vimentin ubiquitination to stabilize vimentin and promote metastasis. Co-immunoprecipitation, ubiquitination assay, overexpression and knockdown, in vivo metastasis model Nature communications High 33046716
2022 TRIM16 interacts with Prdx1 (peroxiredoxin 1) and inhibits its phosphorylation, enhancing downstream Nrf2 pathway activity to suppress cardiac hypertrophy. TRIM16 directly interacts with Src kinase and promotes its ubiquitination-dependent degradation, thereby blocking Prdx1 phosphorylation. Interactome analysis, Co-immunoprecipitation, cardiac-specific KO and AAV9-overexpression mice, ubiquitination assay, RNA-seq, siRNA knockdown Circulation research High 35437018
2022 TRIM16 interacts with NLRP3 and promotes K48-linked polyubiquitination of NLRP3, leading to its proteasomal degradation, thereby reducing inflammasome activation, pyroptosis, and inflammation in myocardial ischemia/reperfusion injury. Co-immunoprecipitation, ubiquitination assay, adenoviral TRIM16 overexpression in vivo, Western blot for NLRP3/caspase-1/GSDMD Biochemical and biophysical research communications Medium 36208489
2021 TRIM16 directly binds and ubiquitinates Snail transcriptional repressor, promoting its degradation and suppressing EMT in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assay, overexpression, rescue experiments with Snail siRNA Experimental cell research Medium 34265287
2021 TRIM16 stabilizes RUNX2 protein by decreasing CHIP-mediated K48-linked ubiquitination and degradation of RUNX2, thereby promoting osteogenic differentiation of human periodontal ligament stem cells. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, overexpression, ALP/Alizarin Red staining Frontiers in cell and developmental biology Medium 33490087
2022 TRIM16 promotes pancreatic cancer metastasis and glycolysis in a ligase-independent manner by competing with TRAF3 at the ISIIAQA motif of NF-κB-inducing kinase (NIK), stabilizing NIK and thereby upregulating SIX1 transcription factor expression. Co-immunoprecipitation, ubiquitination assay, domain competition analysis, in vitro and in vivo functional studies American journal of cancer research Medium 36504902
2022 EZH2 promotes DNMT1-mediated methylation of the TRIM16 promoter, leading to transcriptional silencing of TRIM16 in ovarian cancer cells; CRABP2 upregulates EZH2, which in turn suppresses TRIM16 expression to promote EMT. ChIP assay, bisulfite sequencing/methylation assay, Co-immunoprecipitation (CRABP2-EZH2), siRNA knockdown epistasis, in vivo tumor model Environmental toxicology Medium 35442568
2019 RASSF6 negatively regulates TRIM16 by promoting its ubiquitination-dependent degradation, thereby activating cell cycle and EMT pathways to promote esophageal squamous cell carcinoma progression. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown/overexpression, in vivo tumor model Journal of genetics and genomics Medium 31812473
2023 Under high-glucose conditions, TRIM16 promotes lysophagy to degrade damaged lysosomes and suppress neuronal amyloid-β accumulation; TRIM16-mediated lysophagy is activated in a Galectin-3-dependent manner following lysosomal membrane permeabilization. siRNA knockdown, overexpression, immunofluorescence for galectin-3/LAMP1/LC3, LMP detection, Aβ measurement in iPSC-derived neurons Autophagy Medium 37357416
2021 TRIM16 is involved in cigarette smoke-induced lysophagy; impaired TRIM16-mediated lysophagy results in lysosomal dysfunction and accelerated cellular senescence in bronchial epithelial cells. A negative correlation between TRIM16 and galectin-3 was demonstrated in COPD patient cells. siRNA knockdown, Western blot, immunofluorescence for galectin-3/LAMP1, cellular senescence assays, human COPD tissue analysis Journal of immunology Medium 34135057
2023 TRIM16 promotes K63-linked ubiquitination of NRF2, stabilizing it and upregulating antioxidant genes (SQSTM1/NRF2/KEAP1 axis) under H5N1 HPAIV infection conditions. Overexpression, K63-ubiquitination assay, Western blot, antioxidant gene expression analysis Viruses Medium 36851605
2024 TRIM16 facilitates SIRT-1-dependent antioxidant responses; TRIM16 overexpression enhances SIRT-1 expression, and pharmacological SIRT-1 inhibition (EX-527) abolishes TRIM16's protective effects against oxidative stress and muscle atrophy in aged skeletal muscle. Overexpression, siRNA knockdown, SIRT-1 inhibitor EX-527 epistasis, aged mouse model, ROS measurement Journal of cachexia, sarcopenia and muscle Medium 39192479
2023 TRIM16 promotes K48-linked ubiquitination and degradation of phospho-TAK1, thereby arresting JNK and p38MAPK activation; TRIM16 also elevates YAP1 levels and facilitates its nuclear translocation to promote Nrf2 expression and mitigate oxidative stress in doxorubicin-induced cardiotoxicity. Co-immunoprecipitation, ubiquitination assay, AAV9-TRIM16 overexpression in mice, siRNA knockdown, TAK1 inhibitor epistasis, Western blot for p-TAK1/YAP/Nrf2 Biochemical pharmacology Medium 38154547
2025 TRIM16 catalyzes K63-linked ubiquitination of the endocytic adaptor DAB2 at residue K656 via its SPRY domain (which also mediates the interaction with DAB2's proline-rich domain), promoting endocytosis of integrin β1 and activation of FAK-STAT3 signaling to exacerbate vascular calcification. Immunoprecipitation-mass spectrometry, co-immunoprecipitation, K63-ubiquitination assay, SPRY domain deletion mutants, smooth muscle cell-specific TRIM16 KO mice, siRNA knockdown Circulation research High 40575853
2025 TRIM16 (EBBP) interacts with GRP78 and promotes its K63-linked ubiquitination, disrupting the inhibitory GRP78-PERK interaction and activating PERK-mediated integrated stress response (ISR), leading to ATF4/Nrf2 activation and upregulation of the SLC7A11/GSH/GPX4 axis to suppress ferroptosis in cardiomyocytes. Co-immunoprecipitation, ubiquitination assay, bulk RNA-seq, molecular docking, cardiac-specific EBBP overexpression, PERK inhibitor epistasis Advanced science Medium 40491313
2025 TRIM16 mediates secretory autophagy in cancer-associated fibroblasts; TRIM16 knockdown reduces autophagosomes at the plasma membrane and decreases IL6 secretion. TRIM16 colocalizes with LC3B, IL6, SEC22B, SNAP23, VAMP3, and STX4 in autophagosomes trafficking to the plasma membrane. Transmission electron microscopy, live-cell imaging, immunofluorescence, LC3B immunoprecipitation-mass spectrometry, proximity ligation assay, siRNA knockdown, ELISA for IL6 Autophagy Medium 40383937
2025 TRIM16 directly binds Snai1 (Snail) and promotes its K48-linked ubiquitination at K146, leading to Snail degradation and promotion of ferroptosis in fibroblast-like synoviocytes; Snail overexpression reverses the pro-ferroptotic effect of TRIM16. Co-immunoprecipitation, ubiquitination assay with site-specific Snai1 mutation (K146), overexpression and knockdown, lipid ROS/Fe2+/GSH measurements International immunopharmacology Medium 40991993
2025 TRIM16 interacts with TRAF2 and facilitates its ubiquitination, thereby impeding NF-κB signaling and reducing expression of inflammatory mediators (IL-6, TNF-α, iNOS) in macrophages and a colitis model. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, LPS-stimulated RAW264.7 cells, DSS-induced colitis mouse model, Western blot for NF-κB pathway Journal of cellular and molecular medicine Medium 41134044
2025 TRIM16 directly binds Snai1 and promotes its K48-linked ubiquitination. Additionally, TRIM16 mediates K63-linked ubiquitination of YAP1, facilitating its nuclear translocation to enhance Nrf2 activation and protect against sepsis-induced acute liver injury. Co-immunoprecipitation, ubiquitination assay, siRNA and AAV9-overexpression, in vivo CLP sepsis model, Western blot for YAP/Nrf2 Cell & bioscience Medium 41437125
2024 TRIM16 promotes ubiquitination-mediated degradation of Galectin-3 (Gal-3); NPRL2 increases TRIM16 expression via inactivation of ERK1/2, resulting in reduced Gal-3 secretion from glioma cells and prevention of CD8+ T cell cuproptosis. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown/overexpression, ERK1/2 signaling inhibition, clinical specimen correlation analysis Cellular and molecular life sciences Medium 39367988
2024 TRIM16 promotes K48-linked ubiquitination and proteasomal degradation of NFKBIZ, thereby modulating NFκB signaling in hepatocellular carcinoma; this TRIM16/NFKBIZ/NFκB axis contributes to sorafenib insensitivity. Co-immunoprecipitation, protein degradation assay, flow cytometry, Western blot, immunofluorescence Cellular and molecular life sciences Medium 38581570
2026 TRIM16 promotes ubiquitination and autophagic degradation of Keap1, activating Nrf2-mediated antioxidant genes; additionally, TRIM16 ubiquitinates the iron import receptor TFR1 and targets it for p62-dependent autophagic degradation, reducing iron accumulation and lipid peroxidation in TDP43 proteinopathy. Overexpression, ubiquitination assay, multi-omics analysis, mitochondrial integrity assay, ferroptosis markers, siRNA knockdown Free radical biology & medicine Medium 42092406
2026 FGF8 acts as a molecular scaffold to recruit TRIM16 to RIG-I; TRIM16 mediates K48-linked polyubiquitination of RIG-I at K258, promoting its proteasomal degradation and enabling influenza A virus immune evasion. K258R mutation in RIG-I prevents its TRIM16-mediated degradation. TurboID proximity labeling, Co-immunoprecipitation, K48-ubiquitination assay, RIG-I K258R site-directed mutagenesis, gain- and loss-of-function assays, IFN-β reporter assay Virulence High 42171628
2026 TRIM16 promotes K27-linked polyubiquitination of SARS-CoV-2 ORF3a, targeting it for proteasomal degradation; ZDHHC18-mediated palmitoylation at ORF3a Cys130/Cys133 competitively inhibits this TRIM16-dependent ubiquitination, stabilizing ORF3a and enhancing viral pathogenesis. Co-immunoprecipitation, ubiquitination assay, palmitoylation assay, site-directed mutagenesis (Cys130/133, K27), viral replication assays Advanced science Medium 42107085
2025 TRIM16 acts as an E3 ubiquitin ligase for OPTN (optineurin), promoting its ubiquitin-mediated proteasomal degradation, thereby suppressing mitophagy; in glioblastoma cells, Sanggenol L upregulates TRIM16 expression, and TRIM16 depletion or OPTN overexpression abrogates SL-induced mitophagy suppression and apoptosis. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, OPTN overexpression rescue, in vitro and in vivo GBM models Advanced science Medium 40990506
2025 TRIM16 mediates K63-linked ubiquitination of FGF7 and promotes its degradation; exosomal METTL14 enhances TRIM16 mRNA stability via m6A methylation, increasing TRIM16 expression which limits FGF7-driven breast cancer proliferation and metastasis under hypoxia. Co-immunoprecipitation, ubiquitination assay, MeRIP, RIP assay, dual-luciferase reporter assay, xenograft model Breast cancer research Medium 40796898
2013 Genetic variation in Trim16 promoter leads to strain-dependent expression in the mouse lung; overexpression of Trim16 by plasmid injection increased pulmonary fibrosis, bronchoalveolar lavage IL-12/23-p40, and neutrophils in bleomycin-treated mice, linking Trim16 expression levels to fibrosis susceptibility. Positional cloning, congenic mouse strains, promoter sequence variation analysis, plasmid-based overexpression in vivo, BAL cytokine measurement PLoS genetics Medium 23341783

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 TRIM16 controls assembly and degradation of protein aggregates by modulating the p62-NRF2 axis and autophagy. The EMBO journal 129 30143514
2020 AKT-induced lncRNA VAL promotes EMT-independent metastasis through diminishing Trim16-dependent Vimentin degradation. Nature communications 110 33046716
2012 TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other TRIM family members. PloS one 101 22629402
2022 The E3 Ligase TRIM16 Is a Key Suppressor of Pathological Cardiac Hypertrophy. Circulation research 71 35437018
2010 TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. Oncogene 60 20729920
2013 TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization. Cell cycle (Georgetown, Tex.) 44 23422002
2018 Downregulation of MicroRNA-135 Promotes Sensitivity of Non-Small Cell Lung Cancer to Gefitinib by Targeting TRIM16. Oncology research 41 29295721
2020 Withaferin A activates TRIM16 for its anti-cancer activity in melanoma. Scientific reports 37 33184347
2023 TRIM16-mediated lysophagy suppresses high-glucose-accumulated neuronal Aβ. Autophagy 32 37357416
2014 TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells. Oncotarget 31 25333256
2009 The estrogen-responsive B box protein (EBBP) restores retinoid sensitivity in retinoid-resistant cancer cells via effects on histone acetylation. Cancer letters 31 19147277
2011 The retinoid signalling molecule, TRIM16, is repressed during squamous cell carcinoma skin carcinogenesis in vivo and reduces skin cancer cell migration in vitro. The Journal of pathology 30 22009481
1998 The novel estrogen-responsive B-box protein (EBBP) gene is tamoxifen-regulated in cells expressing an estrogen receptor DNA-binding domain mutant. Molecular endocrinology (Baltimore, Md.) 30 9817599
2019 Galectin-3 and TRIM16 coregulate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells at least partly via enhancing autophagy. Bone 27 31521826
2019 TRIM16 governs the biogenesis and disposal of stress-induced protein aggregates to evade cytotoxicity: implication for neurodegeneration and cancer. Autophagy 26 30806139
2013 TRIM16 overexpression induces apoptosis through activation of caspase-2 in cancer cells. Apoptosis : an international journal on programmed cell death 26 23404198
2020 TRIM16 protects from OGD/R-induced oxidative stress in cultured hippocampal neurons by enhancing Nrf2/ARE antioxidant signaling via downregulation of Keap1. Experimental cell research 23 32251645
2015 Long noncoding ribonucleic acid specific for distant metastasis of gastric cancer is associated with TRIM16 expression and facilitates tumor cell invasion in vitro. Journal of gastroenterology and hepatology 23 25866896
2022 TRIM16 exerts protective function on myocardial ischemia/reperfusion injury through reducing pyroptosis and inflammation via NLRP3 signaling. Biochemical and biophysical research communications 21 36208489
2022 CircPTK2 inhibits cell cisplatin (CDDP) resistance by targeting miR-942/TRIM16 axis in non-small cell lung cancer (NSCLC). Bioengineered 19 35230201
2022 CRABP2 accelerates epithelial mesenchymal transition in serous ovarian cancer cells by promoting TRIM16 methylation via upregulating EZH2 expression. Environmental toxicology 19 35442568
2021 Impaired TRIM16-Mediated Lysophagy in Chronic Obstructive Pulmonary Disease Pathogenesis. Journal of immunology (Baltimore, Md. : 1950) 19 34135057
2020 TRIM16 protects human periodontal ligament stem cells from oxidative stress-induced damage via activation of PICOT. Experimental cell research 18 33091421
2021 TRIM16 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating CHIP-Mediated Degradation of RUNX2. Frontiers in cell and developmental biology 17 33490087
2021 TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation. Experimental cell research 16 34265287
2020 Long non-coding RNA CASC2 induces apoptosis and autophagy in human colon cancer cells via modulation of TRIM16 expression. American journal of translational research 16 32655801
2016 TRIM16 suppresses the progression of prostate tumors by inhibiting the Snail signaling pathway. International journal of molecular medicine 16 27748839
2024 TRIM16 facilitates SIRT-1-dependent regulation of antioxidant response to alleviate age-related sarcopenia. Journal of cachexia, sarcopenia and muscle 14 39192479
2023 Overexpression of TRIM16 Reduces the Titer of H5N1 Highly Pathogenic Avian Influenza Virus and Promotes the Expression of Antioxidant Genes through Regulating the SQSTM1-NRF2-KEAP1 Axis. Viruses 14 36851605
2023 Upregulation of TRIM16 mitigates doxorubicin-induced cardiotoxicity by modulating TAK1 and YAP/Nrf2 pathways in mice. Biochemical pharmacology 14 38154547
2013 Positional cloning reveals strain-dependent expression of Trim16 to alter susceptibility to bleomycin-induced pulmonary fibrosis in mice. PLoS genetics 14 23341783
2022 TRIM16 promotes aerobic glycolysis and pancreatic cancer metastasis by modulating the NIK-SIX1 axis in a ligase-independent manner. American journal of cancer research 13 36504902
2016 A TRIM16-Galactin3 Complex Mediates Autophagy of Damaged Endomembranes. Developmental cell 13 27728777
2018 LncRNA CASC2 inhibits autophagy and promotes apoptosis in non-small cell lung cancer cells via regulating the miR-214/TRIM16 axis. RSC advances 12 35557905
2024 NFKBIZ regulates NFκB signaling pathway to mediate tumorigenesis and metastasis of hepatocellular carcinoma by direct interaction with TRIM16. Cellular and molecular life sciences : CMLS 11 38581570
2022 TRIM3 and TRIM16 as potential tumor suppressors in breast cancer patients. BMC research notes 11 36180926
2019 Heterozygous loss of keratinocyte TRIM16 expression increases melanocytic cell lesions and lymph node metastasis. Journal of cancer research and clinical oncology 11 31342168
2019 RASSF6-TRIM16 axis promotes cell proliferation, migration and invasion in esophageal squamous cell carcinoma. Journal of genetics and genomics = Yi chuan xue bao 10 31812473
2016 A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner. Oncotarget 9 27447557
2024 TRIM16 mitigates impaired osteogenic differentiation and antioxidant response in D-galactose-induced senescent osteoblasts. European journal of pharmacology 8 39059569
2018 TRIM16 controls turnover of protein aggregates by modulating NRF2, ubiquitin system, and autophagy: implication for tumorigenesis. Molecular & cellular oncology 8 30525100
2018 TRIM16 employs NRF2, ubiquitin system and aggrephagy for safe disposal of stress-induced misfolded proteins. Cell stress 8 31225461
2025 EBBP-Mediated Integrated Stress Response Attenuates Anthracycline-Induced Cardiotoxicity by Inhibiting the Ferroptosis of Cardiomyocytes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 40491313
2025 TRIM16 Mediates K63-Linked Ubiquitination of DAB2 to Facilitate Vascular Calcification. Circulation research 7 40575853
2024 TRIM16 and PRC1 Are Involved in Pancreatic Cancer Progression and Targeted by Delphinidin. Chemical biology & drug design 7 39635962
2023 Cordyceps cicadae polysaccharides attenuate diabetic nephropathy via the miR-30a-3p/TRIM16 axis. Journal of diabetes investigation 7 38149724
2024 NPRL2 promotes TRIM16-mediated ubiquitination degradation of Galectin-3 to prevent CD8+T lymphocyte cuproptosis in glioma. Cellular and molecular life sciences : CMLS 6 39367988
2023 TRIM16 Overexpression in HEK293T Cells Results in Cell Line-Specific Antiviral Activity. Pathogens (Basel, Switzerland) 6 37375542
2022 Characterization of TRIM16, a member of the fish-specific finTRIM family, in olive flounder Paralichthys olivaceus. Fish & shellfish immunology 6 35803510
2019 Transcription factors Brn-3α and TRIM16 in cancers, association with hormone reception. Heliyon 6 31463379
2025 TRIM16 mediates secretory autophagy in head and neck cancer-associated fibroblasts. Autophagy 5 40383937
2025 Exosome-delivered METTL14 drives hypoxia-induced proliferation, metastasis, and glycolysis of breast cancer cells through regulating TRIM16-mediated FGF7 ubiquitination. Breast cancer research : BCR 5 40796898
2025 Sanggenol L Enhances Temozolomide Drug Sensitivity by Inhibiting Mitophagy and Inducing Apoptosis Through the Regulation of the TRIM16-OPTN Axis in Glioblastoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 40990506
2024 TFEB ameliorates DEHP-induced neurotoxicity by activating GAL3/TRIM16 axis dependent lysophagy and alleviating lysosomal dysfunction. Environmental toxicology 5 38488668
2023 ZnO nanoparticles impair autophagic flux and cell viability through the TRIM16-NRF2-p62 pathway in inflammatory keratinocytes. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 5 37977258
2022 Changes in the Expression of Long Non-Coding RNA SDMGC and Its Target Gene, TRIM16, in Patients with Gastric Cancer. Journal of gastrointestinal cancer 5 34978663
2018 Reception of Sex Steroid Hormones in Thyroid Papillary Cancer Tissue and Relationship with Expression and Content of Transcription Factors Brn-3α and TRIM16. Bulletin of experimental biology and medicine 4 30488195
2025 The protective role of TRIM16 in rheumatoid arthritis: mechanisms of modulating ferroptosis. International immunopharmacology 2 40991993
2026 TRIM16: a context-dependent E3 ligase in autophagy, oxidative stress, and immune regulation - from cancer and systemic disease. Frontiers in oncology 1 41717414
2025 Xuebijing Exerts Protective Effects on Myocardial Cells by Upregulating TRIM16 and Inhibiting Oxidative Stress and Apoptosis. Current computer-aided drug design 1 39623713
2025 TRIM16 Inhibits Inflammation by Interacting With and Ubiquitinating TRAF2 in a Colitis Model. Journal of cellular and molecular medicine 1 41134044
2022 Expression of concern: LncRNA CASC2 inhibits autophagy and promotes apoptosis in non-small cell lung cancer cells via regulating the miR-214/TRIM16 axis. RSC advances 1 35427090
2026 TRIM16 attenuates TDP43-mediated oxidative injury by coordinating Nrf2 activation and TFR1 autophagic degradation. Free radical biology & medicine 0 42092406
2026 ZDHHC18-Mediated Palmitoylation of ORF3a Promotes SARS-CoV-2 Pathogenesis by Antagonizing TRIM16-Mediated Ubiquitination and Proteasomal Degradation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 42107085
2026 FGF8-mediated TRIM16 regulation promotes K48-linked ubiquitination and degradation of RIG-I to facilitate Influenza a virus immune evasion. Virulence 0 42171628
2025 TRIM16 mediates YAP1 K63-linked ubiquitination to alleviate sepsis-induced acute liver injury through YAP/Nrf2 axis in mice. Cell & bioscience 0 41437125
2024 Retraction: Downregulation of microRNA-135 promotes sensitivity of non-small cell lung cancer to gefitinib by targeting TRIM16. Oncology research 0 39449813
2023 [Retracted] TRIM16 suppresses the progression of prostate tumors by inhibiting the Snail signaling pathway. International journal of molecular medicine 0 37264967

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