Affinage

TRIP12

E3 ubiquitin-protein ligase TRIP12 · UniProt Q14669

Length
2067 aa
Mass
228.5 kDa
Annotated
2026-04-28
57 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIP12 is a HECT-domain E3 ubiquitin ligase that assembles diverse ubiquitin chain topologies—including K29, K11, K48, and branched chains—to target a broad substrate repertoire for proteasomal or lysosomal degradation, thereby governing DNA damage responses, cell cycle progression, Wnt signaling, TGF-β signaling, and the oxidative stress response. Key substrates include RNF168 (limiting histone ubiquitin spreading at DNA break sites) (PMID:22884692), PARP1 (modulating PARP inhibitor sensitivity) (PMID:32755579), FBW7 (via K11-branched chains controlling MCL1 stability) (PMID:33824312), glucocerebrosidase (regulating α-synuclein accumulation and dopaminergic neuron survival) (PMID:34644545), BRG1 (recruiting SWI/SNF to β-catenin at Wnt target genes) (PMID:40473626), and NRF2 (cooperating with CUL3-KEAP1 to silence the oxidative stress response) (PMID:40928944). TRIP12 also performs ligase-independent functions: its N-terminal intrinsically disordered region drives chromatin condensate formation that alters genome accessibility and cell cycle timing (PMID:41660270), and it recruits SMURF2 to SMAD4 to suppress TGF-β signaling independently of catalytic activity (PMID:37863914). Homozygous loss of TRIP12 catalytic activity causes embryonic lethality in mice with growth arrest and p16 upregulation (PMID:22028794).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2008 High

    Establishing TRIP12 as the dedicated E3 ligase of the ubiquitin fusion degradation (UFD) pathway resolved how aberrant ubiquitin-fusion proteins are recognized and cleared, and revealed a noncovalent ubiquitin-binding site in the HECT domain required for substrate engagement.

    Evidence In vitro ubiquitination reconstitution with HECT domain mutagenesis, cross-linking, and siRNA knockdown in human cells

    PMID:19028681

    Open questions at the time
    • E4 cofactor identity for UFD pathway elongation not fully defined
    • Structural basis of the noncovalent ubiquitin-binding site unresolved
  2. 2008 High

    Demonstration that TRIP12 ubiquitinates APP-BP1 (a NEDD8-activating enzyme subunit) and controls its proteasomal turnover linked TRIP12 to regulation of the neddylation cascade, expanding its role beyond UFD substrates.

    Evidence Yeast two-hybrid, co-immunoprecipitation, in vitro ubiquitination, and siRNA knockdown with CUL1 neddylation readout

    PMID:18627766

    Open questions at the time
    • Whether TRIP12 regulation of neddylation has physiological consequences in vivo not tested
    • E4 requirement for APP-BP1 polyubiquitination not molecularly defined
  3. 2011 High

    Genetic inactivation of Trip12 catalytic activity in mice established that its E3 ligase function is essential for embryogenesis, identified BAF57 (SWI/SNF subunit) as an in vivo substrate, and linked TRIP12 loss to p16 de-repression.

    Evidence Homozygous knock-in catalytic-dead mutation in mice; ES cell assays; western blot for BAF57 and p16

    PMID:22028794

    Open questions at the time
    • Whether p16 is a direct or indirect TRIP12 target not resolved
    • Tissue-specific requirements during embryogenesis not defined
  4. 2012 High

    Discovery that TRIP12 (and UBR5) limit RNF168 accumulation to prevent excessive histone ubiquitylation spreading at DNA damage sites established TRIP12 as a rheostat for the DNA damage response, explaining how 53BP1 and BRCA1 foci are confined to break-proximal chromatin.

    Evidence siRNA depletion of TRIP12/UBR5 with immunofluorescence for 53BP1/BRCA1/ubiquitin conjugates and RNF168 protein level measurement

    PMID:22884692

    Open questions at the time
    • Whether TRIP12 directly ubiquitinates RNF168 in vitro not shown in this study
    • Relative contributions of TRIP12 versus UBR5 not fully deconvolved
  5. 2016 Medium

    Identification of USP7 as a TRIP12 substrate linked TRIP12 to control of p53 stability and cell cycle transitions, revealing that TRIP12 indirectly tunes the p53 axis by degrading a key deubiquitinase.

    Evidence Co-immunoprecipitation, siRNA knockdown, overexpression, and FACS cell cycle analysis

    PMID:27800609

    Open questions at the time
    • In vitro ubiquitination of USP7 by TRIP12 not demonstrated
    • Direct ubiquitination sites on USP7 not mapped
  6. 2020 High

    Mapping TRIP12's WWE domain as the PAR-binding module that targets PARP1 for HECT-dependent ubiquitylation and degradation explained how TRIP12 loss sensitizes cells to PARP inhibitors through increased PARP1 trapping, providing a pharmacologically actionable mechanism.

    Evidence Domain mapping, in vitro ubiquitination, PARP1 trapping assay, clonogenic survival after PARPi treatment

    PMID:32755579

    Open questions at the time
    • Chain linkage specificity on PARP1 not determined
    • Whether PAR binding is required for all TRIP12 substrates unclear
  7. 2020 Medium

    Characterization of cell-cycle-dependent TRIP12 expression and its N-terminal IDR-mediated euchromatin association revealed a catalytic-activity-independent role in controlling DNA replication timing and mitotic entry, separating enzymatic from structural functions.

    Evidence Cell cycle synchronization, chromatin fractionation, catalytic mutant complementation, live imaging

    PMID:31964993

    Open questions at the time
    • Molecular mechanism by which IDR binding to chromatin controls replication timing unknown
    • Whether IDR function requires specific chromatin readers not tested
  8. 2021 High

    Demonstration that TRIP12 assembles K29-linked chains that seed K29/K48-branched ubiquitin chains on substrates (shown for PROTAC-recruited BRD4) established TRIP12 as a ubiquitin chain architecture specialist that accelerates proteasomal targeting through branched chain formation.

    Evidence Mass spectrometry-based ubiquitin linkage analysis, in vitro ubiquitination reconstitution, CRISPR KO, PROTAC degradation assays

    PMID:33567268

    Open questions at the time
    • Whether K29/K48 branching is a general feature of all TRIP12 substrates not known
    • Structural basis for K29 linkage preference not resolved
  9. 2021 High

    Identification of glucocerebrosidase (GCase) K293 as a TRIP12 ubiquitination site linked TRIP12 to Parkinson's disease pathogenesis: TRIP12-driven GCase degradation causes α-synuclein accumulation and dopaminergic neurodegeneration, reversible by TRIP12 conditional knockout.

    Evidence Site-directed mutagenesis, conditional KO mouse, α-synuclein PFF model, human PD brain tissue analysis

    PMID:34644545

    Open questions at the time
    • Whether TRIP12 inhibition is therapeutically viable for PD not tested in primates
    • Upstream signals controlling TRIP12-GCase interaction unknown
  10. 2021 High

    Revealing that TRIP12 builds K11-branched ubiquitin chains on FBW7 (at K404/K412) to drive its degradation connected TRIP12 to indirect stabilization of MCL1 and chemotherapy resistance, providing a mechanistic basis for TRIP12 inactivation as a sensitization strategy.

    Evidence shRNA library screen, MS-based linkage analysis, in vitro ubiquitination, FBW7 mutagenesis, CRISPR KO

    PMID:33824312

    Open questions at the time
    • Whether K11-branched chains are assembled by TRIP12 alone or require an E4 cofactor not fully resolved
    • Quantitative contribution of FBW7 self-ubiquitylation priming versus TRIP12-initiated ubiquitylation unclear
  11. 2023 High

    Demonstration that TRIP12 suppresses TGF-β signaling entirely independently of its catalytic activity—by recruiting SMURF2 to monoubiquitinate SMAD4—established a paradigm-shifting non-enzymatic adaptor function conserved from Drosophila to mammals.

    Evidence Catalytic mutant C1959A rescue of TRIP12-KO phenotype, co-IP of SMURF2-SMAD4, TGF-β reporter assays, Drosophila ctrip/Medea genetic epistasis

    PMID:37863914

    Open questions at the time
    • Binding interface between TRIP12 and SMURF2 not structurally resolved
    • Whether this adaptor function extends to other signaling pathways unknown
  12. 2023 Medium

    Establishing that TRIP12 depletion induces EMT through ZEB1/2 upregulation positioned TRIP12 as a suppressor of mesenchymal transition, though whether this occurs through direct ZEB1/2 ubiquitination or an indirect transcriptional mechanism remains open.

    Evidence siRNA knockdown, RNA-seq, ZEB1/2 double-KD rescue of EMT markers, migration and anoikis assays

    PMID:33963176

    Open questions at the time
    • Whether ZEB1/2 are direct TRIP12 substrates not determined
    • Contribution of TRIP12 ligase activity versus adaptor function to EMT suppression not tested
  13. 2025 Medium

    Discovery that TRIP12 ubiquitylates Pol-β in a BER-complex-dependent manner, promoting its chromatin loading at damage sites to favor base excision repair over DSB repair, revealed TRIP12 as a repair pathway choice factor whose overactivity paradoxically increases DSBs and radiosensitivity.

    Evidence Ubiquitination assays, chromatin fractionation, Pol-β foci formation after IR, clonogenic survival, CRISPR depletion

    PMID:40613707

    Open questions at the time
    • Ubiquitin chain type on Pol-β not identified
    • Whether this mechanism operates in non-irradiated cells during normal BER not tested
  14. 2025 High

    Showing that TRIP12 ubiquitylates BRG1 to promote its interaction with β-catenin at Wnt target genes—conserved across Drosophila, zebrafish, mouse, and human cells—placed TRIP12 as a positive regulator of canonical Wnt signaling acting downstream of the β-catenin destruction complex.

    Evidence CRISPR/siRNA in four model organisms, co-IP of BRG1-β-catenin, ubiquitination assays, Wnt reporter assays, genetic epistasis

    PMID:40473626

    Open questions at the time
    • Chain linkage type on BRG1 not determined
    • Whether TRIP12-mediated BRG1 ubiquitination is degradative or non-degradative not fully clarified
  15. 2025 Medium

    Identification of TRIP12 as a ubiquitin chain elongation factor cooperating with CUL3-KEAP1 to degrade NRF2 explained how the oxidative stress response is rapidly silenced once ROS are cleared, adding NRF2 to the catalog of TRIP12 substrates requiring E3–E3 cooperation.

    Evidence CRISPR KO, NRF2 degradation and ubiquitin chain assays, oxidative stress and oxeiptosis cell viability assays

    PMID:40928944

    Open questions at the time
    • Chain linkage specificity on NRF2 by TRIP12 not determined
    • Whether TRIP12 functions similarly with other CRL E3 ligases beyond CUL3-KEAP1 and CRL2-VHL not explored
  16. 2026 Medium

    Demonstration that the TRIP12 N-terminal IDR drives chromatin condensate formation through bridging-induced phase separation, independently of catalytic activity, unified earlier observations of IDR-dependent chromatin binding with a biophysical mechanism and showed these condensates alter genome accessibility and transcription.

    Evidence Live-cell imaging, FRAP, IDR deletion/mutation constructs, ATAC-seq, transcriptome analysis, catalytic mutant controls

    PMID:41660270

    Open questions at the time
    • Whether condensate formation is required for TRIP12's ligase-dependent functions unknown
    • Biophysical parameters (valency, saturation concentration) not quantitatively defined
    • In vivo relevance of condensates in organismal physiology not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete structural model of full-length TRIP12 is lacking, and the rules governing substrate selectivity among its many targets—particularly how WWE-domain PAR binding, IDR-mediated chromatin association, and HECT-domain chain-type specificity are coordinated—remain unresolved.
  • No high-resolution structure of full-length TRIP12 available
  • Mechanisms determining K29 versus K11 versus K48 chain selectivity per substrate unknown
  • How TRIP12 ligase-dependent and ligase-independent functions are spatiotemporally coordinated in vivo not understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 12 GO:0016874 ligase activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-73894 DNA Repair 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-8953897 Cellular responses to stimuli 1
Partners
BRG1FBW7GBAPARP1RNF168SMAD4SMURF2USP7

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 TRIP12 and UBR5, two HECT domain E3 ubiquitin ligases, control accumulation of RNF168 by promoting its degradation via ubiquitylation, thereby limiting spreading of histone ubiquitin conjugates (H2A-Ub) beyond DNA double-strand break sites and preventing hyperaccumulation of 53BP1 and BRCA1 at undamaged chromatin. siRNA depletion of TRIP12/UBR5, immunofluorescence of 53BP1/BRCA1/ubiquitin conjugates, western blot for RNF168 levels, DSB-induced focus formation assays Cell High 22884692
2008 TRIP12 HECT domain functions as the E3 ubiquitin ligase of the human ubiquitin fusion degradation (UFD) pathway, catalyzing in vitro ubiquitination of UFD substrates (including UBB+1) in conjunction with E1, E2, and E4 enzymes; the HECT domain possesses a noncovalent ubiquitin-binding site required for substrate recognition. In vitro ubiquitination assay, siRNA knockdown, cell death assays, cross-linking of HECT domain to ubiquitin moiety in vivo, complementation with HECT domain alone The Journal of biological chemistry High 19028681
2008 TRIP12 interacts with APP-BP1 (NEDD8-activating enzyme subunit) specifically as a monomer (not as APP-BP1/Uba3 heterodimer), ubiquitinates it in vitro requiring E4 activity for polyubiquitination, and promotes its proteasomal degradation, thereby modulating neddylation of CUL1. Yeast two-hybrid, co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown with western blot, neddylation assay of CUL1 Biochemical and biophysical research communications High 18627766
2011 The E3 ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis; homozygous catalytic inactivation causes embryonic lethality with growth arrest and p16 upregulation; Trip12 targets BAF57 (SWI/SNF component) for degradation and regulates global gene expression. Homozygous knock-in mutation disrupting HECT catalytic activity, mouse embryology, ES cell growth and differentiation assays, western blot for BAF57 and p16 PloS one High 22028794
2012 HUWE1 and TRIP12 function in parallel (additive stabilization upon double knockdown) during UFD substrate degradation; HUWE1 associates with both the UFD substrate Ub(G76V)-YFP and the 26S proteasome, acting late in the pathway. High-throughput siRNA imaging screen, single/double knockdown, pulse-chase degradation assays, co-immunoprecipitation with proteasome PloS one Medium 23209776
2016 TRIP12 functions as an E3 ubiquitin ligase for USP7/HAUSP, controlling its protein stability; TRIP12 knockdown increases USP7-mediated stabilization of p53, 53BP1, and Chk1 and increases the G1 cell population, while TRIP12 overexpression phenocopies USP7 knockdown by increasing intra-S phase cells. Co-immunoprecipitation, siRNA knockdown, overexpression, western blot, cell cycle analysis by FACS FEBS letters Medium 27800609
2020 TRIP12 binds PARP1 via its central PAR-binding WWE domain and, via its C-terminal HECT domain, catalyzes polyubiquitylation of PARP1 triggering proteasomal degradation; loss of TRIP12 elevates PARP1 levels, causing increased PARPi-induced cytotoxic PARP1 trapping, replication stress, and cell death. Co-immunoprecipitation, in vitro ubiquitination, siRNA knockdown, PARP1 trapping assay, cell viability/clonogenic survival, domain mapping (WWE and HECT) Cell reports High 32755579
2021 TRIP12 promotes PROTAC/CRL2VHL-induced degradation of neo-substrate BRD4 (but not endogenous HIF-1α) by associating with BRD4 via CRL2VHL and specifically assembling K29-linked ubiquitin chains that facilitate formation of K29/K48-branched ubiquitin chains, accelerating K48 chain elongation and proteasomal degradation. Mass spectrometry-based ubiquitin linkage analysis, in vitro ubiquitination, siRNA/CRISPR knockout, PROTAC degradation assays, domain mapping, apoptosis assays Molecular cell High 33567268
2021 TRIP12 interacts with glucocerebrosidase (GCase) and ubiquitinates it at lysine 293, triggering proteasomal degradation; TRIP12 overexpression causes premature GCase degradation, α-synuclein accumulation, and mitochondrial dysfunction; conditional TRIP12 knockout or knockdown promotes GCase expression and blocks dopaminergic neurodegeneration in PD models. Co-immunoprecipitation, in vitro ubiquitination, site-directed mutagenesis (K293), TRIP12 conditional KO mouse, in vivo knockdown, α-syn PFF model, western blot, human PD brain tissue analysis Neuron High 34644545
2021 TRIP12 ubiquitinates FBW7 preferentially on K404/K412 (via SCFFBW7 self-ubiquitylation) and additionally assembles K11-linked branched ubiquitin chains on FBW7 via its HECT domain; this branched ubiquitylation is required for FBW7 proteasomal degradation; TRIP12 inactivation causes FBW7 accumulation and consequent MCL1 degradation, sensitizing cells to anti-tubulin chemotherapy. shRNA library screen, mass spectrometry, in vitro ubiquitination, site-directed mutagenesis of FBW7 K404/K412, CRISPR knockout, western blot, cell viability assays Nature communications High 33824312
2020 TRIP12 expression is regulated during the cell cycle correlating with its nuclear localization; an N-terminal intrinsically disordered region (IDR) mediates euchromatin binding; TRIP12 controls duration of DNA replication (mitotic entry) independent of its catalytic activity, and is required for mitotic progression and chromosome stability. Cell cycle synchronization, western blot, immunofluorescence/live imaging, chromatin fractionation, siRNA knockdown, catalytic mutant complementation, FACS for chromosome stability Scientific reports Medium 31964993
2021 WARS (tryptophanyl-tRNA synthetase) tryptophanylates TRIP12 at lysine 1136, activating its E3 ligase activity toward NFATc1 (a PD-1 transcription activator), promoting NFATc1 degradation and reducing PD-1 surface expression on CD8+ T cells; SIRT1 de-tryptophanylates TRIP12 and reverses these effects. Mass spectrometry identification of tryptophanylation, site-directed mutagenesis (K1136), co-immunoprecipitation, flow cytometry for surface PD-1, syngeneic mouse tumor models Journal for immunotherapy of cancer Medium 34326168
2020 TRIP12 is identified by immunoprecipitation-coupled LC-MS/MS as an E3 ubiquitin ligase that binds and ubiquitinates the transcription factor YY1, leading to its proteasomal degradation; this triggers the HNF4α/miR-122/CCL2 pathway promoting hepatic inflammation during mild iron overload. Immunoprecipitation coupled LC-MS/MS, co-immunoprecipitation, western blot, siRNA knockdown, overexpression in vivo Free radical biology & medicine Medium 33080340
2023 TRIP12 controls TGFβ signaling in a manner completely independent of its E3 ubiquitin ligase activity; instead, TRIP12 recruits SMURF2 to SMAD4, promoting inhibitory monoubiquitination of SMAD4; catalytically inactive C1959A mutant rescues TRIP12-KO phenotype; this function is evolutionarily conserved (Drosophila ctrip/Medea epistasis confirmed). CRISPR/Cas9 KO, catalytic mutant complementation (C1959A), co-immunoprecipitation of SMURF2-SMAD4, TGFβ reporter assays, Drosophila genetic epistasis, 3D intestinal organoids, migration assays Cell death & disease High 37863914
2025 TRIP12 ubiquitylates DNA polymerase β (Polβ) in a BER complex-dependent manner, controlling Polβ cellular levels and chromatin loading; TRIP12-mediated Polβ ubiquitylation promotes Polβ foci formation at radiation-induced DNA damage sites, directing BER over DSB repair; excessive TRIP12-mediated Polβ engagement increases DSB formation and radiation sensitivity. Ubiquitination assays, chromatin fractionation, siRNA/CRISPR depletion, Polβ foci formation (immunofluorescence), radiation sensitivity/clonogenic assays, co-immunoprecipitation Nucleic acids research Medium 40613707
2025 TRIP12 ubiquitylates BRG1 (SWI/SNF component) in the presence of Wnt signaling, promoting BRG1 interaction with β-catenin in the nucleus to recruit SWI/SNF to Wnt target genes; TRIP12 depletion attenuates Wnt signaling; genetic epistasis places TRIP12 downstream of the β-catenin destruction complex. CRISPR/siRNA depletion in Drosophila, zebrafish, mouse organoids, human cells; co-immunoprecipitation of BRG1-β-catenin; ubiquitination assays; genetic epistasis; Wnt reporter assays Nature communications High 40473626
2025 TRIP12 functions as a ubiquitin chain elongation factor that cooperates with CUL3KEAP1 to ensure robust NRF2 degradation; TRIP12 activity accelerates silencing of the oxidative stress response as ROS are cleared but limits NRF2 activation during stress. CRISPR KO, NRF2 degradation assays, ubiquitin chain assays, oxidative stress/ROS assays, cell viability after oxeiptosis Cell reports Medium 40928944
2025 TRIP12 ubiquitinates Frizzled-9b (Fzd9b) at K437 in its third intracellular loop, targeting it for lysosomal degradation, reducing Fzd9b membrane surface expression and dampening Wnt9a/Fzd9b signaling; this semi-selective action affects hematopoietic stem cell proliferation in zebrafish. Site-directed mutagenesis of Fzd9b K437, ubiquitination assays, flow cytometry for surface Fzd9b, zebrafish HSC proliferation assay, lysosome inhibitor experiments, co-immunoprecipitation iScience Medium 41098776
2024 K29-linked ubiquitylation of SUV39H1 (H3K9me3 methyltransferase) is catalyzed by TRIP12 and reversed by TRABID; K29-linked ubiquitylation is essential for proteasomal degradation of SUV39H1 even in the presence of extensive K48-linked ubiquitylation; disruption of this modification deregulates the H3K9me3 landscape. Ubiquitin replacement cell-based strategy, MS-based linkage analysis, TRIP12 KO/depletion, in vitro ubiquitination, H3K9me3 ChIP, SUV39H1 stability assays bioRxivpreprint Medium bio_10.1101_2024.10.29.620783
2023 TRIP12 suppresses EMT through inhibiting ZEB1/2 gene expression; TRIP12-depleted cells gain mesenchymal traits (loss of polarity, increased motility, anoikis resistance); ZEB1/2 depletion rescues EMT markers in TRIP12-depleted cells, placing ZEB1/2 downstream of TRIP12. siRNA knockdown of TRIP12, RNA-seq, ZEB1/2 double KD rescue, cell polarity assays, migration assays, anoikis assays Cell death discovery Medium 33963176
2016 p16 overexpression downregulates TRIP12, which leads to increased RNF168 levels, repressed DNA damage repair, increased 53BP1 foci, and enhanced radiosensitivity; TRIP12 inhibition further radiosensitizes cells, establishing a p16→TRIP12→RNF168 regulatory axis. p16 overexpression/shRNA knockdown, western blot for TRIP12 and RNF168, immunofluorescence for 53BP1 foci, clonogenic survival assays, neutral comet assay, cycloheximide half-life assay Oncogene Medium 27425591
2023 TRIP12 associates with Ku70 at sites of DNA double-strand breaks; this association is enhanced upon ionizing radiation and is specific to the Ku70 S155 phosphorylated form, as identified by BioID2 proximity labeling and validated by proximity ligation assay and co-immunoprecipitation. BioID2 proximity labeling, SAINTexpress analysis, proximity ligation assay (PLA), co-immunoprecipitation after IR treatment International journal of molecular sciences Low 37108203
2026 The N-terminal intrinsically disordered region (IDR) of TRIP12 drives formation of dynamic chromatin condensates enriched in heterochromatin marks through electrostatic interactions and bridging-induced phase separation; these condensates alter cell cycle progression, genome accessibility, and transcription independently of TRIP12's ubiquitin ligase activity. Live-cell imaging, FRAP, IDR deletion/mutation constructs, heterochromatin mark staining, ATAC-seq, transcriptome analysis, catalytic mutant controls iScience Medium 41660270

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. Cell 297 22884692
2020 The Ubiquitin Ligase TRIP12 Limits PARP1 Trapping and Constrains PARP Inhibitor Efficiency. Cell reports 103 32755579
2021 Tryptophan potentiates CD8+ T cells against cancer cells by TRIP12 tryptophanylation and surface PD-1 downregulation. Journal for immunotherapy of cancer 88 34326168
2021 TRIP12 promotes small-molecule-induced degradation through K29/K48-branched ubiquitin chains. Molecular cell 74 33567268
2008 The HECT domain of TRIP12 ubiquitinates substrates of the ubiquitin fusion degradation pathway. The Journal of biological chemistry 56 19028681
2020 E3 Ubiquitin Ligase TRIP12: Regulation, Structure, and Physiopathological Functions. International journal of molecular sciences 49 33198194
2016 Identification of new TRIP12 variants and detailed clinical evaluation of individuals with non-syndromic intellectual disability with or without autism. Human genetics 46 27848077
2017 Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes intellectual disability with or without autism spectrum disorders, speech delay, and dysmorphic features. Human genetics 42 28251352
2016 TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects. Oncogene 42 27425591
2016 Trip12 is an E3 ubiquitin ligase for USP7/HAUSP involved in the DNA damage response. FEBS letters 42 27800609
2021 TRIP12 ubiquitination of glucocerebrosidase contributes to neurodegeneration in Parkinson's disease. Neuron 38 34644545
2012 HUWE1 and TRIP12 collaborate in degradation of ubiquitin-fusion proteins and misframed ubiquitin. PloS one 35 23209776
2012 TRADD contributes to tumour suppression by regulating ULF-dependent p19Arf ubiquitylation. Nature cell biology 32 22561347
2020 The E3 ubiquitin ligase TRIP12 participates in cell cycle progression and chromosome stability. Scientific reports 30 31964993
2008 TRIP12 functions as an E3 ubiquitin ligase of APP-BP1. Biochemical and biophysical research communications 30 18627766
2011 The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis. PloS one 27 22028794
2010 Reactivating the ARF-p53 axis in AML cells by targeting ULF. Cell cycle (Georgetown, Tex.) 27 20699639
2021 Proteasomal degradation of the tumour suppressor FBW7 requires branched ubiquitylation by TRIP12. Nature communications 26 33824312
2020 Mild iron overload induces TRIP12-mediated degradation of YY1 to trigger hepatic inflammation. Free radical biology & medicine 26 33080340
2010 The TRIP from ULF to ARF. Cancer cell 16 20385357
2023 The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant. European journal of human genetics : EJHG 15 36747006
2024 circEPB41L2 blocks the progression and metastasis in non-small cell lung cancer by promoting TRIP12-triggered PTBP1 ubiquitylation. Cell death discovery 13 38341427
2014 Nucleostemin stabilizes ARF by inhibiting the ubiquitin ligase ULF. Oncogene 13 24769896
2021 The oncogenic E3 ligase TRIP12 suppresses epithelial-mesenchymal transition (EMT) and mesenchymal traits through ZEB1/2. Cell death discovery 12 33963176
2015 Creating a gold standard surgical device: scientific discoveries leading to TVT and beyond: Ulf Ulmsten Memorial Lecture 2014. International urogynecology journal 12 25693655
2022 Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome. International journal of molecular sciences 11 36430143
2023 Small molecule Z363 co-regulates TAF10 and MYC via the E3 ligase TRIP12 to suppress tumour growth. Clinical and translational medicine 8 36639831
2020 Novel de novo TRIP12 mutation reveals variable phenotypic presentation while emphasizing core features of TRIP12 variations. American journal of medical genetics. Part A 8 32424948
2025 TRIP12's role in the governance of DNA polymerase β involvement in DNA damage response and repair. Nucleic acids research 7 40613707
2024 Spectroscopic and imaging considerations of THz-TDS and ULF-Raman techniques towards practical security applications. Optics express 7 38297686
2023 Analysis of the PARP1, ADP-Ribosylation, and TRIP12 Triad With Markers of Patient Outcome in Human Breast Cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 6 36990278
2023 Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12. Cell death & disease 6 37863914
2014 RNA-Seq analysis identifies aberrant RNA splicing of TRIP12 in acute myeloid leukemia patients at remission. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 5 24961348
2023 E3 Ubiquitin Ligase TRIP12 Controls Exit from Mitosis via Positive Regulation of MCL-1 in Response to Taxol. Cancers 4 36672454
2022 Novel Synonymous and Frameshift Variants in the TRIP12 Gene Identified in 2 Chinese Patients With Intellectual Disability. Neurology. Genetics 4 36275919
2025 Helicobacter pylori activates DOPEY1 to promote p53 degradation through the USP7/TRIP12 axis in gastric tumorigenesis. Oncogene 3 39939725
2025 Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12. Cell reports 3 40928944
2024 The E3 ubiquitin ligase TRIP12 is required for pancreatic acinar cell plasticity and pancreatic carcinogenesis. The Journal of pathology 3 38924548
2025 The Role of a Novel TRIP12 Mutation in Intellectual Disability: A Molecular and Clinical Investigation in Multiplex Family. Journal of molecular neuroscience : MN 2 40172777
2024 Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation. Journal of Cancer 2 38706891
2024 Engineered targeting OIP5 sensitizes bladder cancer to chemotherapy resistance via TRIP12-PPP1CB-YBX1 axis. Oncogene 2 39155295
2024 High sensitivity measurement of ULF, VLF, and LF fields with a Rydberg-atom sensor. Optics letters 2 39353003
2024 Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12. bioRxiv : the preprint server for biology 2 39651249
2023 Analysis of Ku70 S155 Phospho-Specific BioID2 Interactome Identifies Ku Association with TRIP12 in Response to DNA Damage. International journal of molecular sciences 2 37108203
2000 Immunolocalization of uterine luminal fluid protein (ULF-250) in rat uterus. Chinese medical journal 2 11776035
2024 TRIP12 governs DNA Polymerase β involvement in DNA damage response and repair. bioRxiv : the preprint server for biology 1 38645048
2021 [Intellectual disability due to heterozygous c.40C>T variant of TRIP12 gene in a patient]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 33565064
1996 Characterization of a uterine luminal fluid protein ULF-250 using N-terminal microsequencing and RT-PCR identifies a novel estrogen-regulated gene in the rat uterus. FEBS letters 1 8980114
2026 miR-381-3p suppresses pterygium progression by regulating HACE1/TRIP12-mediated ubiquitin-degradation of MCPIP1. In vitro cellular & developmental biology. Animal 0 41611982
2026 The TRIP12's intrinsically disordered region induces chromatin condensates and interferes with nuclear processes. iScience 0 41660270
2025 Unraveling the Molecular and Clinical Consequences of an Intragenic TRIP12 Duplication Using Genomic and RNA Analyses. American journal of medical genetics. Part A 0 40062706
2025 The TRIP12 E3 ligase induces SWI/SNF component BRG1-β-catenin interaction to promote Wnt signaling. Nature communications 0 40473626
2025 USP7 overexpression prevents the progression of clear cell renal cell carcinoma by enhancing pyroptosis via TRIP12 deubiquitination. Cancer biology & therapy 0 40947978
2025 The E3 ubiquitin ligase Trip12 semi-selectively attenuates Wnt signaling. iScience 0 41098776
2025 Novel TRIP12 variants in two Lebanese patients with neurodevelopmental delay. BMC medical genomics 0 41413819
2025 Neurodevelopmental Phenotype Associated with TRIP12: Report of a Family Carrying the p.Asp1135Val Variant. Genes 0 41465129
2024 The E3 Ubiquitin Ligase Trip12 attenuates Wnt9a/Fzd9b signaling during hematopoietic stem cell development. bioRxiv : the preprint server for biology 0 39484584