Affinage

TRIM16

Tripartite motif-containing protein 16 · UniProt O95361

Length
564 aa
Mass
64.0 kDa
Annotated
2026-04-28
65 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM16 is an atypical TRIM-family E3 ubiquitin ligase that uses RING-like B-box domains to catalyze both K48- and K63-linked ubiquitination of a broad substrate repertoire, functioning as a central coordinator of proteostasis, selective autophagy, antioxidant defense, and inflammatory signaling. It stabilizes NRF2 through K63-linked ubiquitination within the p62-KEAP1-NRF2 complex and scaffolds p62, ULK1, ATG16L1, and LC3B onto protein aggregates and damaged lysosomes to drive aggrephagy and lysophagy (PMID:30143514, PMID:37357416, PMID:34135057). TRIM16 ubiquitinates and targets for degradation diverse substrates including vimentin (K48), Snail (K48, K146), NLRP3 (K48), TRAF2, Src, OPTN, NFKBIZ, DAB2, and FGF7, thereby suppressing EMT, inflammasome activation, and NF-κB signaling in context-dependent manners (PMID:33046716, PMID:34265287, PMID:36208489, PMID:35437018, PMID:40575853). TRIM16 undergoes dynamic nuclear-cytoplasmic shuttling during the cell cycle, directly binds and downregulates E2F1 to inhibit G1/S progression, and binds the IFNβ1 promoter to regulate migration (PMID:20729920, PMID:23422002, PMID:25333256).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 Medium

    The initial identification of TRIM16 (EBBP) as an estrogen/antiestrogen-regulated cytoplasmic B-box protein established it as a hormonally controlled gene of unknown function, setting the stage for later mechanistic work.

    Evidence Northern blot, subcellular fractionation, and ER mutant epistasis in breast cancer cells

    PMID:9817599

    Open questions at the time
    • No enzymatic activity characterized
    • No substrates identified
    • Mechanism of antiestrogen regulation via mutant ER unclear
  2. 2009 Medium

    Discovery that TRIM16 associates with histone acetylation and de-represses RARβ2 transcription while inhibiting cell growth via cyclin D1/phospho-Rb established TRIM16 as a transcription-associated growth suppressor, though the mechanism was unclear.

    Evidence Reporter assays and western blotting for cell cycle proteins in neuroblastoma cells

    PMID:19147277

    Open questions at the time
    • No direct enzymatic mechanism defined
    • Histone acetyltransferase association indirect
    • Single cell line context
  3. 2010 High

    Identification of vimentin and E2F1 as direct TRIM16 binding partners, and demonstration of retinoid-induced nuclear translocation, established TRIM16 as a dual-compartment regulator of migration and replication.

    Evidence Co-immunoprecipitation, subcellular fractionation, and siRNA rescue in neuroblastoma and SCC cells

    PMID:20729920 PMID:22009481

    Open questions at the time
    • Mechanism of vimentin/E2F1 downregulation unknown (degradation vs. transcriptional)
    • Nuclear translocation signal uncharacterized
  4. 2012 High

    Structural and biochemical demonstration that TRIM16 possesses E3 ubiquitin ligase activity through its B-box domains (not a classical RING) resolved the fundamental question of how an atypical TRIM protein catalyzes ubiquitination.

    Evidence 3D structural modelling, in vitro and in vivo ubiquitination assays, domain deletion mutants, Co-IP for TRIM24/PML/MID1 heterodimerization

    PMID:22402

    Open questions at the time
    • No crystal structure obtained
    • Physiological substrates not yet linked to this ligase activity
    • E2 partner preference undefined
  5. 2013 Medium

    Characterization of cell-cycle-dependent nuclear-cytoplasmic shuttling of TRIM16 and its interaction with caspase-2 expanded the functional model to include G1/S checkpoint control and apoptosis induction.

    Evidence Cell cycle synchronization with domain deletion mutants, caspase-2 Co-IP and activity assays in neuroblastoma/breast cancer cells

    PMID:23404198 PMID:23422002

    Open questions at the time
    • Nuclear localization signal within TRIM16 not mapped
    • Direct caspase-2 activation mechanism unclear
    • Caspase-2 interaction not confirmed by independent group
  6. 2014 Medium

    ChIP evidence that TRIM16 directly binds the IFNβ1 promoter and controls migration/proliferation in an IFNβ1-dependent manner revealed a direct transcriptional regulatory function beyond ubiquitin ligase activity.

    Evidence Chromatin immunoprecipitation, epistasis with IFNβ1 knockdown in melanoma cells

    PMID:25333256

    Open questions at the time
    • Mechanism of transcriptional activation at the promoter not defined
    • Whether TRIM16 acts as a transcription factor or co-factor unclear
    • Single cancer type tested
  7. 2018 High

    The pivotal discovery that TRIM16 stabilizes NRF2 via K63-linked ubiquitination within the p62-KEAP1-NRF2 complex and scaffolds autophagy machinery (p62, ULK1, ATG16L1, LC3B) onto aggregates unified TRIM16's ligase and scaffolding functions into a coherent aggrephagy pathway.

    Evidence Co-IP, ubiquitination assays with linkage specificity, autophagy flux analysis, in vivo stress models

    PMID:30143514 PMID:30806139

    Open questions at the time
    • Structural basis of scaffold assembly unknown
    • Whether TRIM16 ubiquitinates autophagy adaptors directly or only NRF2 unclear
    • Relative contribution of ligase vs. scaffold function not dissected
  8. 2020 High

    Demonstration that TRIM16 ubiquitinates vimentin for proteasomal degradation — and that lncRNA VAL competitively blocks this interaction — provided the first defined ubiquitination substrate linking TRIM16 ligase activity to EMT suppression.

    Evidence Ubiquitination assay, RNA pulldown, competitive binding experiments in hepatocellular carcinoma

    PMID:33046716

    Open questions at the time
    • Ubiquitin chain linkage type on vimentin not specified
    • Whether other lncRNAs similarly regulate TRIM16 substrate access unknown
  9. 2021 Medium

    Expansion of the substrate repertoire to Snail (K48-linked degradation suppressing EMT), NLRP3 (K48-linked degradation suppressing inflammasome), and damaged lysosomes (galectin-3-dependent lysophagy) established TRIM16 as a multi-substrate ligase with context-dependent anti-inflammatory and proteostatic roles.

    Evidence Co-IP and ubiquitination assays with epistasis rescue for Snail/NLRP3; galectin-3 puncta and senescence assays in COPD tissues and iPSC neurons

    PMID:34135057 PMID:34265287 PMID:36208489 PMID:37357416

    Open questions at the time
    • How TRIM16 selects among diverse substrates is unknown
    • Lysophagy mechanism details (galectin-3–TRIM16 structural interface) not resolved
    • NLRP3 finding from single lab
  10. 2022 High

    Identification of Src kinase as a TRIM16 substrate (ubiquitination and degradation) in cardiac hypertrophy, and of TRAF2/NFKBIZ as substrates suppressing NF-κB signaling, broadened the functional scope to cardioprotection and inflammatory homeostasis.

    Evidence Unbiased interactome followed by Co-IP and ubiquitination assays; cardiac-specific knockout mice (Src); DSS colitis model (TRAF2); HCC cells (NFKBIZ)

    PMID:35437018 PMID:38581570 PMID:41134044

    Open questions at the time
    • Whether Src ubiquitination uses K48 or K63 linkage not specified
    • TRAF2 ubiquitin chain type not defined
    • Cardiac-specific vs. systemic functions not fully delineated
  11. 2024 High

    Site-specific mapping of TRIM16-mediated K63-linked ubiquitination of DAB2 at K656 via the SPRY domain, promoting integrin β1 endocytosis, demonstrated a non-degradative signaling role and identified the SPRY domain as a substrate-recognition module.

    Evidence IP-MS, Co-IP, site-mapping ubiquitination assay, smooth muscle-specific TRIM16 knockout mice in CKD models

    PMID:40575853

    Open questions at the time
    • Whether SPRY domain mediates recognition of other substrates not tested
    • Pro-calcification role contrasts with generally protective functions — context-dependency not resolved
  12. 2025 Medium

    Recent studies identified additional substrates (FGF7, OPTN, YAP1, GRP78) and a secretory autophagy function, revealing that TRIM16 regulates mitophagy suppression (via OPTN degradation), integrated stress response activation (via GRP78 K63-ubiquitination/PERK release), ferroptosis modulation (via Snail K48-ubiquitination at K146), and unconventional IL-6 secretion from cancer-associated fibroblasts.

    Evidence Co-IP, linkage- and site-specific ubiquitination assays, LC3B proteomics, cardiac overexpression models, GBM xenografts, CAF imaging

    PMID:40383937 PMID:40491313 PMID:40796898 PMID:40990506 PMID:41437125

    Open questions at the time
    • Secretory autophagy mechanism and cargo selection not fully defined
    • GRP78 ubiquitination as PERK activator requires independent validation
    • How TRIM16 simultaneously promotes lysophagy/aggrephagy yet suppresses mitophagy is paradoxical and unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for TRIM16's substrate selectivity among its many targets, the E2 ubiquitin-conjugating enzyme partners, the mechanism distinguishing its K48 vs. K63 linkage specificity, and how its ligase-dependent vs. scaffold-dependent functions are regulated remain open questions.
  • No crystal or cryo-EM structure of TRIM16
  • E2 conjugating enzyme specificity undefined
  • Mechanism governing K48 vs. K63 linkage choice unknown
  • Relative in vivo contribution of ligase vs. scaffold function not genetically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-392499 Metabolism of proteins 10 R-HSA-9612973 Autophagy 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 1 R-HSA-5357801 Programmed Cell Death 1
Partners
DAB2LGALS3NRF2SNAI1SQSTM1TRIM24ULK1VIM
Complex memberships
p62-KEAP1-NRF2 complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 TRIM16, despite lacking a classical RING domain, possesses E3 ubiquitin ligase activity via its B-box domains which adopt RING-like folds; it undergoes auto-polyubiquitination and catalyzes ubiquitination in vitro and in vivo. 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, domain deletion mutants PloS one High 22629402
2010 TRIM16 directly binds cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells; overexpression reduces cell motility (requiring vimentin downregulation) and translocates to the nucleus upon retinoid treatment to downregulate E2F1 and inhibit cell replication. Co-immunoprecipitation, subcellular fractionation, immunofluorescence, siRNA knockdown, overexpression with phenotypic readouts (migration, growth) Oncogene High 20729920
2009 TRIM16 (EBBP) acts as a histone acetylase-associated protein that increases histone acetylation and de-represses RARβ2 and CYP26A1 transcription via the βRARE regulatory sequence; it inhibits cell growth through effects on cyclin D1 and phospho-Rb. Chromatin modifying agent treatments, overexpression, reporter assays, western blotting for cyclin D1 and phospho-Rb Cancer letters Medium 19147277
2011 In squamous cell carcinoma cells, TRIM16 directly binds and downregulates nuclear E2F1 (required for replication) and directly binds and downregulates vimentin (required for reduced migration); the C-terminal RFP-like domain of TRIM16 is required for reduced cell migration. Nuclear translocation of TRIM16 is induced by retinoid treatment. Co-immunoprecipitation, domain deletion mutants, overexpression/knockdown with migration and proliferation assays, immunofluorescence The Journal of pathology High 22009481
2013 TRIM16 exhibits dynamic nuclear-cytoplasmic localization during cell cycle progression: TRIM16 protein is upregulated and shifts to the nucleus during G1 phase. An uncharacterized domain within TRIM16 is required for both its nuclear localization and its growth inhibitory effects. TRIM16 regulates G1/S progression through changes in Cyclin D1 and p27 expression. Immunohistochemistry in TH-MYCN mouse model, cell cycle synchronization, TRIM16 deletion mutants, western blotting Cell cycle (Georgetown, Tex.) Medium 23422002
2013 TRIM16 directly interacts with caspase-2 protein in breast cancer and neuroblastoma cells, co-localizes with caspase-2, increases procaspase-2 protein levels, and activates caspase-2 activity; caspase-2 activation is required for TRIM16-induced apoptosis. Co-immunoprecipitation, co-localization by immunofluorescence, caspase activity assays, overexpression with apoptosis readouts Apoptosis : an international journal on programmed cell death Medium 23404198
2014 TRIM16 directly binds the IFNβ1 gene promoter (shown by chromatin immunoprecipitation) and regulates cell migration and proliferation in melanoma cells in an IFNβ1-dependent manner. BRAF inhibitor vemurafenib induces melanoma growth arrest in a TRIM16-dependent manner. Chromatin immunoprecipitation (ChIP), overexpression/knockdown with migration and proliferation assays, epistasis with IFNβ1 knockdown Oncotarget Medium 25333256
2018 TRIM16 is an integral component of the p62-KEAP1-NRF2 complex; it stabilizes NRF2 via K63-linked ubiquitination, activating p62 and ubiquitin pathway genes, which leads to ubiquitination of misfolded proteins and protein aggregate formation. TRIM16 also acts as a scaffold protein that recruits p62, ULK1, ATG16L1, and LC3B to protein aggregates to facilitate their autophagic degradation (aggrephagy). Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, overexpression, autophagy flux analysis, in vitro and in vivo stress models The EMBO journal High 30143514
2019 TRIM16 controls K63-linked ubiquitination and stabilization of NRF2 (enhancing NRF2 activation), which upregulates SQSTM1/p62 and ubiquitin pathway proteins; TRIM16 physically localizes around protein aggregates and recruits SQSTM1 and autophagy initiation proteins (ULK1, ATG16L1, LC3B) to sequester aggregates into autophagosomes for degradation. Co-immunoprecipitation, ubiquitination assays, immunofluorescence, autophagy assays Autophagy High 30806139
2016 RASSF6 promotes ubiquitination-dependent degradation of TRIM16, negatively regulating TRIM16 protein levels in esophageal squamous cell carcinoma and thereby activating cell cycle and EMT pathways. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown with phenotypic readouts Journal of genetics and genomics = Yi chuan xue bao Medium 31812473
2020 TRIM16 mediates polyubiquitination and proteasomal degradation of vimentin; the lncRNA VAL competes with TRIM16 binding to vimentin to prevent its ubiquitination and degradation, thereby stabilizing vimentin and promoting invasion. Co-immunoprecipitation, ubiquitination assay, RNA pulldown, competitive binding experiments, loss-of-function assays Nature communications High 33046716
2021 TRIM16 directly binds and ubiquitinates Snail (Snail family transcriptional repressor 1) to promote its degradation, suppressing EMT in colorectal cancer; inhibition of Snail degradation abolishes the anti-metastatic effect of TRIM16. Co-immunoprecipitation, ubiquitination assay, Snail rescue experiments, in vitro and in vivo metastasis assays Experimental cell research Medium 34265287
2019 TRIM16 interacts with Galectin-3 via ULK1 in human bone marrow-derived mesenchymal stem cells; TRIM16 increases stability of ULK1 and Beclin1, and osteogenic induction enhances association between TRIM16 and ULK1/Beclin1, promoting autophagy and osteogenic differentiation. Co-immunoprecipitation, shRNA knockdown, overexpression, LC3 puncta immunofluorescence, ALP and Alizarin Red staining Bone Medium 31521826
2021 TRIM16 interacts with NLRP3 inflammasome and promotes K48-linked polyubiquitination of NLRP3, leading to its proteasomal degradation, thereby suppressing inflammasome activation, pyroptosis (caspase-1 and GSDMD cleavage), and inflammation in myocardial ischemia/reperfusion injury. Co-immunoprecipitation, ubiquitination assay, overexpression via adenoviral vectors in vivo, in vitro cardiomyocyte models Biochemical and biophysical research communications Medium 36208489
2022 TRIM16 interacts with Prdx1 and inhibits its phosphorylation, enhancing downstream Nrf2 pathway activity; TRIM16 also directly interacts with and ubiquitinates Src kinase for its degradation, thereby blocking Prdx1 phosphorylation. This mechanism suppresses pathological cardiac hypertrophy. RNA-sequencing, interactome analysis, co-immunoprecipitation, ubiquitination assay, cardiac-specific knockout mice and AAV9 overexpression mice, transverse aortic constriction model Circulation research High 35437018
2021 TRIM16 promotes osteogenic differentiation of human periodontal ligament stem cells by stabilizing RUNX2 protein: TRIM16 decreases CHIP-mediated K48-linked ubiquitination and degradation of RUNX2 without affecting RUNX2 mRNA levels. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, overexpression, ALP/Alizarin Red staining Frontiers in cell and developmental biology Medium 33490087
2022 EZH2 promotes DNMT1-mediated methylation of the TRIM16 promoter CpG island, leading to transcriptional silencing of TRIM16 in ovarian cancer cells; CRABP2 upregulates EZH2 to indirectly suppress TRIM16 expression. ChIP assay for DNMT1 enrichment at TRIM16 promoter, methylation analysis, co-immunoprecipitation (EZH2-CRABP2), siRNA knockdown/overexpression Environmental toxicology Medium 35442568
2023 TRIM16 overexpression promotes K63-linked poly-ubiquitination of NRF2 (under basal conditions), activating the SQSTM1/NRF2/KEAP1 antioxidant pathway and reducing H5N1 avian influenza virus titer in A549 cells. Overexpression, ubiquitination assays specifying K63-linkage, antioxidant gene expression analysis, viral titer measurement Viruses Medium 36851605
2022 TRIM16 interacts with TRAF2 and promotes its ubiquitination, impeding NF-κB signaling and reducing inflammatory mediator (IL-6) expression in macrophages and colitis model. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, NF-κB pathway analysis, DSS-induced colitis model Journal of cellular and molecular medicine Medium 41134044
2024 TRIM16 mediates K63-linked ubiquitination of DAB2 at K656 via its SPRY domain, promoting DAB2-dependent endocytosis of integrin β1 and subsequent activation of FAK-STAT3 signaling, exacerbating vascular calcification in CKD. Immunoprecipitation-mass spectrometry, co-immunoprecipitation, ubiquitination assay with domain (SPRY) and site (K656) mapping, siRNA/adenovirus, smooth muscle-specific TRIM16 knockout mice, CKD rat and mouse models Circulation research High 40575853
2023 TRIM16-mediated lysophagy (lysosome-selective autophagy) is activated upon lysosomal membrane permeabilization (detected by galectin-3 accumulation) and suppresses high-glucose-induced amyloid β accumulation in neurons; impaired TRIM16-mediated lysophagy leads to lysosomal dysfunction. siRNA knockdown, overexpression, immunofluorescence for galectin-3 and LC3 puncta, lysosome function assays, iPSC-derived neuronal cells Autophagy Medium 37357416
2021 TRIM16-mediated lysophagy is impaired in COPD; cigarette smoke extract induces lysosomal membrane permeabilization (galectin-3 puncta), and TRIM16 cooperates with galectin-3 to recognize damaged lysosomes and initiate lysophagy; reduced TRIM16 leads to lysosomal dysfunction and accelerated cellular senescence. siRNA knockdown, immunofluorescence, galectin-3 accumulation assay, senescence assays, human COPD lung tissues Journal of immunology (Baltimore, Md. : 1950) Medium 34135057
2025 TRIM16 promotes secretory autophagy in cancer-associated fibroblasts: TRIM16 traffics to autophagosomes, colocalizes with LC3B, IL6, SEC22B, SNAP23, VAMP3, and STX4; TRIM16 knockdown reduces autophagosomes at the plasma membrane and decreases IL6 secretion from CAFs. Transmission electron microscopy, live-cell imaging, immunofluorescence, unbiased LC3B immunoprecipitation proteomics (LC-MS/MS), TRIM16 knockdown, HNSCC patient tissue immunohistochemistry Autophagy Medium 40383937
2024 NPRL2 increases TRIM16 expression via inactivation of ERK1/2 signaling; TRIM16 promotes ubiquitination-mediated degradation of Galectin-3, diminishing Gal-3 release from glioma cells and preventing Gal-3-induced CD8+ T cell cuproptosis. Co-immunoprecipitation, ubiquitination assay, ERK inhibitor treatment, siRNA knockdown, flow cytometry for cuproptosis markers Cellular and molecular life sciences : CMLS Medium 39367988
2025 TRIM16 (EBBP) interacts with GRP78 to promote its K63-linked ubiquitination, disrupting the inhibitory GRP78-PERK interaction and activating PERK-mediated integrated stress response (ISR), which activates ATF4 and Nrf2 to upregulate SLC7A11/GSH/GPX4 axis and restore iron homeostasis, suppressing ferroptosis in anthracycline-induced cardiotoxicity. Bulk RNA-seq, molecular docking, co-immunoprecipitation, ubiquitination assay, cardiac-specific overexpression, PERK inhibitor epistasis, ferroptosis assays Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40491313
2025 TRIM16 directly binds to and ubiquitinates Snai1 via K48-linkage at K146, promoting its degradation, and thereby promotes ferroptosis in TNF-α-stimulated fibroblast-like synoviocytes. Co-immunoprecipitation, ubiquitination assay with K48-linkage specificity and site mapping (K146), lipid ROS measurement, rescue experiments International immunopharmacology Medium 40991993
2025 TRIM16 directly binds and stabilizes YAP1 through K63-linked ubiquitination, facilitating YAP1 nuclear translocation, which enhances Nrf2 activation and antioxidant gene expression to protect against sepsis-induced acute liver injury. Co-immunoprecipitation, K63-linkage specific ubiquitination assay, nuclear fractionation, siRNA/AAV9-overexpression, CLP sepsis model in vivo Cell & bioscience Medium 41437125
2023 TRIM16 modulates TAK1 by ubiquitinating and degrading phospho-TAK1 (p-TAK1), blocking JNK and p38MAPK activation; TRIM16 also elevates YAP levels and facilitates its nuclear translocation, promoting Nrf2 expression and reducing oxidative stress and inflammation in DOX-induced cardiotoxicity. Co-immunoprecipitation, ubiquitination assay, siRNA/AAV9 overexpression, TAK1 inhibitor (Takinib) epistasis, NRCMs and in vivo DOX model Biochemical pharmacology Medium 38154547
2025 TRIM16 acts as an E3 ubiquitin ligase for OPTN (optineurin), promoting its ubiquitin-mediated proteasomal degradation to suppress mitophagy in glioblastoma cells; TRIM16 depletion or OPTN overexpression reverses this suppression of autophagy. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown/overexpression, autophagy flux analysis, GBM xenograft model Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40990506
2022 TRIM16 promotes pancreatic cancer metastasis and aerobic glycolysis in a ligase-independent manner by competing with TRAF3 (NIK's E3 ligase) at the ISIIAQA motif of NIK, thereby stabilizing NIK protein and upregulating SIX1 transcription factor to enhance glycolysis. Co-immunoprecipitation, competitive binding assay, ubiquitination assay, NIK inhibitor treatment, in vitro and in vivo metastasis/glycolysis assays American journal of cancer research Medium 36504902
2025 TRIM16 mediates K63-linked ubiquitination of FGF7, promoting its degradation; METTL14 enhances TRIM16 mRNA stability via m6A methylation, and hypoxia-induced exosomal METTL14 modulates this axis to affect TNBC cell proliferation, metastasis, and glycolysis. Co-immunoprecipitation, ubiquitination assay, MeRIP, RIP, dual-luciferase reporter assay, xenograft tumor model Breast cancer research : BCR Medium 40796898
2024 TRIM16 interacts with NFKBIZ and promotes K48-linked ubiquitination of NFKBIZ, leading to its degradation, which modulates NFκB signaling in hepatocellular carcinoma cells. Co-immunoprecipitation, protein degradation assay, flow cytometry, western blot, immunofluorescence Cellular and molecular life sciences : CMLS Medium 38581570
1998 TRIM16 (EBBP) was identified as an estrogen- and antiestrogen-regulated gene; the encoded protein has predominantly cytoplasmic localization and belongs to the B-box zinc finger protein family. Regulation of EBBP by tamoxifen can occur through a mutated ER that lacks normal estrogen responsiveness, indicating distinct molecular mechanisms for estrogen vs. antiestrogen regulation. Northern blot, subcellular fractionation, cycloheximide sensitivity assay, ER mutant stable transfection Molecular endocrinology (Baltimore, Md.) Medium 9817599

Source papers

Stage 0 corpus · 65 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 126 30143514
2020 AKT-induced lncRNA VAL promotes EMT-independent metastasis through diminishing Trim16-dependent Vimentin degradation. Nature communications 109 33046716
2012 TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other TRIM family members. PloS one 100 22629402
2022 The E3 Ligase TRIM16 Is a Key Suppressor of Pathological Cardiac Hypertrophy. Circulation research 69 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 36 33184347
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
2023 TRIM16-mediated lysophagy suppresses high-glucose-accumulated neuronal Aβ. Autophagy 29 37357416
2019 TRIM16 governs the biogenesis and disposal of stress-induced protein aggregates to evade cytotoxicity: implication for neurodegeneration and cancer. Autophagy 26 30806139
2019 Galectin-3 and TRIM16 coregulate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells at least partly via enhancing autophagy. Bone 26 31521826
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
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
2021 TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation. Experimental cell research 15 34265287
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
2013 Positional cloning reveals strain-dependent expression of Trim16 to alter susceptibility to bleomycin-induced pulmonary fibrosis in mice. PLoS genetics 14 23341783
2023 Upregulation of TRIM16 mitigates doxorubicin-induced cardiotoxicity by modulating TAK1 and YAP/Nrf2 pathways in mice. Biochemical pharmacology 13 38154547
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
2024 TRIM16 facilitates SIRT-1-dependent regulation of antioxidant response to alleviate age-related sarcopenia. Journal of cachexia, sarcopenia and muscle 12 39192479
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
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
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 9 38581570
2016 A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner. Oncotarget 9 27447557
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
2024 TRIM16 mitigates impaired osteogenic differentiation and antioxidant response in D-galactose-induced senescent osteoblasts. European journal of pharmacology 7 39059569
2023 Cordyceps cicadae polysaccharides attenuate diabetic nephropathy via the miR-30a-3p/TRIM16 axis. Journal of diabetes investigation 7 38149724
2024 TRIM16 and PRC1 Are Involved in Pancreatic Cancer Progression and Targeted by Delphinidin. Chemical biology & drug design 6 39635962
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
2025 EBBP-Mediated Integrated Stress Response Attenuates Anthracycline-Induced Cardiotoxicity by Inhibiting the Ferroptosis of Cardiomyocytes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 40491313
2025 TRIM16 Mediates K63-Linked Ubiquitination of DAB2 to Facilitate Vascular Calcification. Circulation research 5 40575853
2024 TFEB ameliorates DEHP-induced neurotoxicity by activating GAL3/TRIM16 axis dependent lysophagy and alleviating lysosomal dysfunction. Environmental toxicology 5 38488668
2024 NPRL2 promotes TRIM16-mediated ubiquitination degradation of Galectin-3 to prevent CD8+T lymphocyte cuproptosis in glioma. Cellular and molecular life sciences : CMLS 5 39367988
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
2019 Transcription factors Brn-3α and TRIM16 in cancers, association with hormone reception. Heliyon 5 31463379
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 4 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 TRIM16 mediates secretory autophagy in head and neck cancer-associated fibroblasts. Autophagy 3 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 3 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) 3 40990506
2025 The protective role of TRIM16 in rheumatoid arthritis: mechanisms of modulating ferroptosis. International immunopharmacology 2 40991993
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: a context-dependent E3 ligase in autophagy, oxidative stress, and immune regulation - from cancer and systemic disease. Frontiers in oncology 0 41717414
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