Affinage

TRIP12

E3 ubiquitin-protein ligase TRIP12 · UniProt Q14669

Length
2067 aa
Mass
228.5 kDa
Annotated
2026-06-10
58 papers in source corpus 29 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIP12 is a HECT-domain E3 ubiquitin ligase whose catalytic activity is essential for mammalian development and which serves as a master regulator of protein turnover across the DNA damage response, cell cycle, protein quality control, and developmental signalling (PMID:22028794). A defining biochemical feature is its ability to assemble atypical and branched ubiquitin chains: it builds K29-linked chains and K29/K48-branched chains that accelerate K48 chain assembly and proteasomal degradation, both on PROTAC neo-substrates recruited via CRL2VHL (PMID:33567268) and on the H3K9me3 methyltransferase SUV39H1, where K29 linkage is required for degradation even in the presence of K48 chains [PMID:bio_10.1101_2024.10.29.620783], and it elongates K11-branched chains on FBW7 to license its destruction (PMID:33824312). In genome maintenance, TRIP12 restricts the spread of chromatin ubiquitylation at double-strand breaks by limiting accumulation of the RNF168 E3 ligase (PMID:22884692), controls steady-state PARP1 levels to limit PARPi-induced PARP1 trapping (PMID:32755579), and ubiquitylates DNA polymerase β to govern its chromatin loading and the balance between base-excision and double-strand-break repair (PMID:40613707). It acts as the human ubiquitin-fusion-degradation (UFD) pathway E3 ligase (PMID:19028681, PMID:23209776) and degrades a broad substrate set including the NEDD8-activating enzyme subunit APP-BP1/NAE1 (PMID:18627766), the deubiquitinase USP7 (PMID:27800609), the tumour suppressor ARF (PMID:20699639), glucocerebrosidase (PMID:34644545), and the transcription factors YY1 and NFATc1 (PMID:34326168, PMID:33080340). TRIP12 also exerts ubiquitin-ligase-independent functions: an N-terminal intrinsically disordered region binds euchromatin and drives chromatin condensate formation that controls cell-cycle progression and genome accessibility (PMID:31964993, PMID:41660270), it scaffolds SMURF2 onto SMAD4 to repress TGFβ signalling (PMID:37863914), and it stabilizes HIV-1 Tat by enhancing the USP7–Tat interaction (PMID:42126234). In Wnt signalling it acts downstream of the β-catenin destruction complex, ubiquitylating BRG1 to promote SWI/SNF recruitment to target genes while also degrading the receptor Frizzled-9b (PMID:40473626, PMID:41098776).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2008 High

    Established TRIP12 as a genuine HECT E3 ligase by defining its enzymatic role in the ubiquitin-fusion-degradation pathway and on the neddylation enzyme subunit APP-BP1, anchoring its catalytic function biochemically.

    Evidence In vitro ubiquitination with E1/E2/E4, cross-linking, yeast two-hybrid, and siRNA knockdown of UFD substrates and APP-BP1

    PMID:18627766 PMID:19028681

    Open questions at the time
    • Full substrate repertoire and chain-linkage preference not yet defined
    • Physiological consequences of APP-BP1 stabilization on global neddylation only partially explored
  2. 2011 High

    Demonstrated that TRIP12 catalytic activity is indispensable in vivo, showing a HECT-domain mutation causes embryonic lethality and linking TRIP12 to SWI/SNF (BAF57) regulation and proliferation.

    Evidence Mouse catalytic knock-in model, ES cell phenotyping, gene expression profiling

    PMID:22028794

    Open questions at the time
    • Critical developmental substrate(s) driving lethality not identified
    • Mechanism linking TRIP12 to BAF57 levels unresolved at this stage
  3. 2012 High

    Positioned TRIP12 as a brake on the DNA damage response by limiting RNF168 accumulation and thereby restricting the spread of chromatin ubiquitylation and 53BP1/BRCA1 recruitment at breaks.

    Evidence siRNA depletion of TRIP12/UBR5, immunofluorescence, DNA damage induction

    PMID:22884692

    Open questions at the time
    • Chain linkage on RNF168 not defined
    • Relative contributions of TRIP12 versus UBR5 not separated
  4. 2012 Medium

    Defined TRIP12 (ULF) as the E3 ligase controlling ARF turnover and the ARF-p53 tumour-suppressor axis, including regulation by TRADD shuttling.

    Evidence siRNA knockdown, cycloheximide chase, p53 response assays, mouse TRADD knockout with senescence assays and co-IP

    PMID:20699639 PMID:22561347

    Open questions at the time
    • Direct ARF ubiquitination by TRIP12 in vitro not shown in these studies
    • Ubiquitin chain type on ARF undefined
  5. 2016 Medium

    Connected TRIP12 to checkpoint control by identifying USP7 as a substrate and placing TRIP12 downstream of p16 in regulating RNF168, DDR, and radiosensitivity.

    Evidence Co-IP, reciprocal gain/loss-of-function, cell cycle analysis, clonogenic survival, comet assay

    PMID:27425591 PMID:27800609

    Open questions at the time
    • No in vitro ubiquitination assay for USP7
    • Direct versus indirect effects on p53/53BP1/Chk1 not fully separated
  6. 2020 High

    Revealed TRIP12 controls PARP1 levels through a WWE-domain PAR-binding mechanism, and uncovered a catalytic-activity-independent chromatin-binding role of its N-terminal IDR in cell-cycle and chromosome stability.

    Evidence Co-IP, domain mapping, in vitro ubiquitination, KO viability assays, subcellular fractionation, chromosome spreads

    PMID:31964993 PMID:32755579

    Open questions at the time
    • Chain architecture on PARP1 not characterized
    • Molecular basis of IDR euchromatin binding not yet structurally defined
  7. 2021 High

    Established TRIP12 as a branched-chain elongation factor that assembles K29-linked and K11/K29/K48-branched ubiquitin chains, accelerating degradation of PROTAC neo-substrates, FBW7, and GCase via lysine-specific modification.

    Evidence CRISPR KO, in vitro ubiquitination, linkage-specific mass spectrometry, site-directed mutagenesis, PROTAC degradation and chemosensitization assays

    PMID:33567268 PMID:33824312 PMID:34644545

    Open questions at the time
    • Determinants of TRIP12 substrate/linkage selectivity unresolved
    • How branched chains are read by the proteasome not addressed here
  8. 2021 Medium

    Showed TRIP12 activity is itself regulated by post-translational modification (WARS-mediated tryptophanylation, reversed by SIRT1) controlling NFATc1 degradation and PD-1 expression on CD8+ T cells.

    Evidence Mass spectrometry, biochemistry, flow cytometry, WARS/SIRT1 manipulation, syngeneic mouse models

    PMID:34326168

    Open questions at the time
    • Structural basis of K1136 tryptophanylation-driven activation unknown
    • Generality of this regulation across other substrates untested
  9. 2023 High

    Defined ubiquitin-ligase-independent functions of TRIP12 in TGFβ repression by scaffolding SMURF2 onto SMAD4, and established roles in EMT suppression and pancreatic tumourigenesis.

    Evidence CRISPR KO with catalytic-dead (C1959A) rescue, co-IP, organoids, Drosophila epistasis; siRNA/RNA-seq EMT assays; conditional KO mouse PDAC models

    PMID:33963176 PMID:37863914 PMID:38924548

    Open questions at the time
    • How TRIP12 selects scaffolding versus catalytic modes is unresolved
    • Mechanism of ZEB1/2 transcriptional repression not defined
  10. 2024 Medium

    Extended TRIP12 into developmental Wnt signalling and chromatin-modifier control, ubiquitylating BRG1 to recruit SWI/SNF to Wnt targets, degrading Frizzled-9b, and assembling K29 chains on SUV39H1 to shape the H3K9me3 landscape.

    Evidence CRISPR/siRNA KO, in vitro ubiquitination, reciprocal co-IP, site mutagenesis, ubiquitin replacement/linkage profiling, epistasis across Drosophila/zebrafish/mouse/human

    PMID:40473626 PMID:41098776 PMID:bio_10.1101_2024.10.29.620783

    Open questions at the time
    • How Wnt switches TRIP12 between BRG1 stabilization and Fzd9b degradation is unclear
    • SUV39H1 finding remains a preprint awaiting peer review
  11. 2025 Medium

    Integrated TRIP12 into oxidative-stress and base-excision-repair control, acting as a chain-elongation factor cooperating with CUL3KEAP1 to degrade NRF2 and ubiquitylating Polβ to govern repair-pathway choice.

    Evidence CRISPR KO, in vitro ubiquitination, NRF2 and Polβ stability/chromatin-loading assays, oxeiptosis and clonogenic survival readouts

    PMID:40613707 PMID:40928944

    Open questions at the time
    • Chain linkage on Polβ not defined
    • How TRIP12 partitions between CUL3KEAP1 cooperation and independent activity unresolved
  12. 2026 Medium

    Demonstrated that the TRIP12 IDR drives bridging-induced chromatin phase separation controlling genome accessibility and that TRIP12 can stabilize substrates non-catalytically, as for HIV-1 Tat via the USP7–Tat interaction.

    Evidence IDR deletion mutants, FRAP, ATAC-seq, biophysical condensate assays; co-IP with catalytic-dead rescue and viral transcription/reactivation assays

    PMID:41660270 PMID:42126234

    Open questions at the time
    • Physiological triggers of condensate formation in vivo unclear
    • How condensate function and ligase function are coordinated remains open

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIP12 selects among dozens of substrates and switches between catalytic ubiquitylation, branched-chain elongation, scaffolding, and phase-separation modes remains the central unresolved question.
  • No structural model integrating HECT, WWE, and IDR domains with substrate/linkage choice
  • Determinants of K29 versus K11 versus branched-chain output undefined
  • Rules governing catalytic versus non-catalytic engagement unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0003677 DNA binding 2 GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2 R-HSA-8953897 Cellular responses to stimuli 1
Partners
BRG1FBW7PARP1SMAD4SMURF2UBR5USP7YY1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 TRIP12 (together with UBR5) controls accumulation of RNF168, a rate-limiting HECT E3 ligase that ubiquitylates histones after DNA double-strand breaks. Depletion of TRIP12 and UBR5 allows supraphysiological RNF168 accumulation, leading to massive spreading of ubiquitin conjugates and hyperaccumulation of 53BP1 and BRCA1, demonstrating that TRIP12 restricts the spread of chromatin ubiquitylation at DNA lesions. siRNA depletion, immunofluorescence, western blotting, DNA damage induction Cell High 22884692
2020 TRIP12 binds PARP1 via a central PAR-binding WWE domain and, using its C-terminal HECT domain, catalyzes polyubiquitylation of PARP1 to trigger proteasomal degradation, thereby controlling steady-state PARP1 levels and limiting PARPi-induced cytotoxic PARP1 trapping. Co-immunoprecipitation, in vitro ubiquitination assay, TRIP12 domain mapping, siRNA/CRISPR KO, cell viability and DNA damage assays Cell reports High 32755579
2021 TRIP12 assembles K29-linked ubiquitin chains on neo-substrates (e.g., BRD4 targeted by CRL2VHL-based PROTACs), facilitating formation of K29/K48-branched ubiquitin chains that accelerate K48 chain assembly by CRL2VHL and promote proteasomal degradation; TRIP12 associates with the neo-substrate via CRL2VHL but is dispensable for degradation of the endogenous CRL2VHL substrate HIF-1α. CRISPR KO, in vitro ubiquitination assay, ubiquitin linkage-specific mass spectrometry, co-immunoprecipitation, PROTAC-induced degradation assays Molecular cell High 33567268
2008 TRIP12 is the E3 enzyme of the human ubiquitin fusion degradation (UFD) pathway: its HECT domain catalyzes in vitro ubiquitination of UFD substrates (including UBB+1) in conjunction with E1, E2, and E4 enzymes, and possesses a noncovalent ubiquitin-binding site; knockdown of TRIP12 stabilizes UFD substrates and reduces UBB+1-induced cell death. In vitro ubiquitination assay, siRNA knockdown, cycloheximide chase, cross-linking, cell death assay The Journal of biological chemistry High 19028681
2008 TRIP12 functions as an E3 ubiquitin ligase for APP-BP1 (NAE1), the regulatory subunit of the NEDD8-activating enzyme: TRIP12 interacts specifically with the APP-BP1 monomer (not the APP-BP1/Uba3 heterodimer) via yeast two-hybrid and co-immunoprecipitation, catalyzes APP-BP1 polyubiquitination in vitro, and its knockdown stabilizes APP-BP1 and increases neddylation of CUL1. Yeast two-hybrid, co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, overexpression Biochemical and biophysical research communications Medium 18627766
2012 HUWE1 and TRIP12 function in parallel (independently) in the UFD pathway: double knockdown of both E3 ligases causes additive stabilization of the UFD substrate Ub(G76V)-YFP, yet ubiquitylation of the substrate persists, revealing functional redundancy with additional E3 ligases. siRNA library screen, high-throughput imaging, co-immunoprecipitation with 26S proteasome, cycloheximide chase PloS one Medium 23209776
2016 TRIP12 functions as an E3 ubiquitin ligase for USP7/HAUSP, controlling USP7 protein stability and consequently affecting USP7-mediated stabilization of p53 and the checkpoint proteins 53BP1 and Chk1; TRIP12 knockdown increased the G1 cell population (mimicking USP7 overexpression) while TRIP12 overexpression increased the intra-S-phase population (mimicking USP7 knockdown). Co-immunoprecipitation, siRNA knockdown, overexpression, cell cycle analysis FEBS letters Medium 27800609
2012 TRADD modulates the interaction between p19ARF and its E3 ubiquitin ligase ULF (TRIP12) by shuttling from cytoplasm to nucleus, thereby promoting p19ARF stability and tumour suppression; TRADD deficiency reduced p19ARF accumulation and attenuated HRas-induced senescence. Mouse knockout model, primary cell senescence assay, subcellular fractionation, co-immunoprecipitation Nature cell biology Medium 22561347
2010 ULF (TRIP12) is a bona fide E3 ubiquitin ligase for ARF: ULF knockdown stabilizes ARF and reactivates p53 responses in AML cells expressing cytoplasmic-dislocated NPM mutant, demonstrating that ULF controls ARF turnover and the ARF-p53 axis. siRNA knockdown, cycloheximide chase, p53 response assays in OCI-AML3 cells Cell cycle (Georgetown, Tex.) Medium 20699639
2011 The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis: a homozygous inactivating mutation in the HECT domain causes embryonic lethality at mid-gestation; Trip12 mutant ES cells are viable but show decreased proliferation, increased BAF57 protein levels (SWI/SNF complex component), and altered gene expression. Mouse knock-in model, ES cell culture, western blotting, gene expression profiling PloS one High 22028794
2021 TRIP12 ubiquitinates glucocerebrosidase (GCase) at lysine 293, triggering its proteasomal degradation; TRIP12-mediated GCase degradation leads to functional GCase impairment, subsequent α-synuclein accumulation, and mitochondrial dysfunction in a Parkinson's disease context. Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis (K293), conditional KO/knockdown, α-syn preformed fibril model in vivo Neuron High 34644545
2021 TRIP12 ubiquitylates FBW7 preferentially on K404/K412 via K11-linked branched ubiquitin chains; SCF(FBW7)-mediated ubiquitylation alone is insufficient for proteasomal degradation and requires this additional TRIP12-mediated branched K11 ubiquitylation. TRIP12 inactivation causes FBW7 accumulation and sensitizes cancer cells to anti-tubulin chemotherapy through increased MCL1 degradation. shRNA library screen, mass spectrometry-based ubiquitin site mapping, CRISPR KO, epistasis (FBW7 co-inactivation rescue) Nature communications High 33824312
2021 WARS (tryptophanyl-tRNA synthetase) tryptophanylates TRIP12 at lysine 1136, activating its E3 ligase activity; activated TRIP12 degrades NFATc1 (a PD-1 transcription activator), thereby downregulating surface PD-1 on CD8+ T cells. SIRT1 de-tryptophanylates TRIP12 and reverses these effects. Mass spectrometry, biochemical analyses, flow cytometry, WARS overexpression, SIRT1 manipulation, in vitro co-culture, syngeneic mouse models Journal for immunotherapy of cancer Medium 34326168
2020 TRIP12 expression is cell-cycle regulated and correlates with its nuclear localization. An N-terminal intrinsically disordered region (IDR) mediates euchromatin binding. TRIP12 controls the duration of DNA replication and mitotic entry independently of its catalytic activity, and is required for mitotic progression and chromosome stability. Cell cycle synchronization, immunofluorescence, subcellular fractionation, CRISPR KO, siRNA knockdown, chromosome spread assays Scientific reports Medium 31964993
2020 TRIP12 binds and ubiquitinates the transcription factor YY1, leading to its proteasomal degradation; this TRIP12/YY1 axis controls HNF4α/miR-122/CCL2 signaling and hepatic inflammation under mild iron overload conditions. Immunoprecipitation coupled LC-MS/MS, co-immunoprecipitation, in vivo mouse model, YY1 overexpression/silencing Free radical biology & medicine Medium 33080340
2016 p16 overexpression leads to downregulation of TRIP12, which in turn increases RNF168 levels and represses DNA damage repair, increases 53BP1 foci, and enhances radioresponsiveness, placing TRIP12 downstream of p16 in a pathway controlling DDR and radiosensitivity. siRNA knockdown, overexpression, clonogenic survival, western blotting, cycloheximide chase, 53BP1 immunofluorescence, comet assay Oncogene Medium 27425591
2014 Nucleostemin (NS) stabilizes ARF by inhibiting its E3 ligase ULF (TRIP12): NS overexpression suppresses ARF polyubiquitination by ULF and extends ARF half-life, while NS knockdown decreases ARF levels; NS can also enhance NPM-mediated ARF stabilization. Affinity purification/mass spectrometry, co-immunoprecipitation, in vitro and in vivo ubiquitination assays, cycloheximide chase Oncogene Medium 24769896
2023 TRIP12 controls TGFβ signalling independently of its E3 ubiquitin ligase catalytic activity: TRIP12 recruits SMURF2 to SMAD4, promoting inhibitory SMAD4 monoubiquitination; loss of TRIP12 robustly activates TGFβ signalling, and rescue with a catalytically inactive C1959A mutant fully restores normal signalling. This function is evolutionarily conserved in Drosophila. CRISPR/Cas9 KO, catalytic mutant rescue, co-immunoprecipitation, 3D organoids, Drosophila genetic epistasis Cell death & disease High 37863914
2025 TRIP12 is a ubiquitin chain elongation factor that cooperates with CUL3KEAP1 to ensure robust NRF2 degradation; TRIP12 promotes NRF2 turnover during recovery from oxidative stress, limiting NRF2 activation during stress and accelerating stress response silencing as ROS are cleared. CRISPR KO, in vitro ubiquitination assay, NRF2 stability assays, cell death readouts (oxeiptosis), epistasis with CUL3KEAP1 Cell reports Medium 40928944
2025 TRIP12 ubiquitylates DNA polymerase β (Polβ) in a BER complex-dependent manner, controlling cellular levels and chromatin loading of Polβ; TRIP12, but not its partner UBR5, regulates Polβ foci formation after radiation-induced DNA damage, and excessive TRIP12-mediated Polβ engagement promotes BER precedence over DSB repair, affecting DSB formation and radiation sensitivity. In vitro ubiquitination assay, CRISPR/siRNA KO, chromatin fractionation, immunofluorescence (Polβ foci), clonogenic survival Nucleic acids research Medium 40613707
2025 TRIP12 ubiquitylates the SWI/SNF component BRG1 in the presence of Wnt, promoting BRG1–β-catenin interaction in the nucleus and recruitment of SWI/SNF to Wnt target genes; genetic epistasis places TRIP12 downstream of the β-catenin destruction complex, and TRIP12 depletion attenuates Wnt signalling in Drosophila, zebrafish, mouse organoids, and human cells. CRISPR/siRNA KO, co-immunoprecipitation, in vitro ubiquitination assay, genetic epistasis across multiple model organisms, luciferase reporter assays Nature communications High 40473626
2024 TRIP12 selectively ubiquitinates the third intracellular loop of Frizzled-9b (Fzd9b) at K437, targeting it for lysosomal degradation and reducing Fzd9b surface expression, thereby dampening Wnt9a/Fzd9b signalling and affecting hematopoietic stem cell proliferation in zebrafish. CRISPR/siRNA KO in zebrafish, site-directed mutagenesis (K437), flow cytometry for surface receptor levels, in vivo HSC proliferation assay iScience Medium 41098776
2024 K29-linked ubiquitylation of the H3K9me3 methyltransferase SUV39H1 is catalyzed by TRIP12 and reversed by TRABID; K29-linked ubiquitylation is essential for proteasomal degradation of SUV39H1 even in the presence of K48-linked ubiquitylation, and disruption of this modification deregulates the H3K9me3 landscape. Ubiquitin replacement strategy (cell-based), linkage-specific ubiquitin chain profiling, TRIP12 KO, K29 chain assembly assay bioRxivpreprint Medium bio_10.1101_2024.10.29.620783
2023 TRIP12 suppresses epithelial-mesenchymal transition (EMT) by inhibiting ZEB1/2 gene expression; TRIP12 depletion causes an EMT shift, loss of cell polarity, increased cellular motility, and ZEB1/2 depletion rescues EMT markers in TRIP12-depleted cells. siRNA depletion, RNA-seq, EMT marker western blotting, cell motility/polarity assays, anoikis assay, epistasis by ZEB1/2 co-depletion Cell death discovery Medium 33963176
2023 TRIP12 promotes BRD4 degradation by PROTAC-bound CRL2VHL but is dispensable for the degradation of the endogenous CRL2VHL substrate HIF-1α; TRIP12 associates with BRD4 via CRL2VHL and preferentially assembles K29-linked ubiquitin chains. (Replicated finding from PMID:33567268, additional mechanistic detail from a separate paper.) shRNA screen, co-immunoprecipitation, in vitro ubiquitination assay, mass spectrometry Molecular cell High 33567268
2026 TRIP12 stabilizes HIV-1 Tat independently of its own E3 ligase activity by enhancing the interaction between deubiquitinase USP7 and Tat, thereby reducing K48-linked ubiquitination of Tat and inhibiting its proteasomal degradation; TRIP12 KO reduces USP7–Tat interaction, accelerates Tat degradation, and suppresses viral transcription and latency reactivation. Co-immunoprecipitation, catalytic mutant (E3 ligase-dead) rescue, TRIP12 KO, viral transcription and reactivation assays Journal of virology Medium 42126234
2023 Small molecule Z363 activates TRIP12, which directly ubiquitinates and degrades MYC (following MYC phosphorylation at Thr58) and also induces degradation of TAF10, indirectly reducing MYC levels; TRIP12 thus controls MYC stability both directly and via TAF10. CRISPR KO, western blotting, cell culture degradation assays, mouse tumor models Clinical and translational medicine Low 36639831
2026 TRIP12's N-terminal intrinsically disordered region (IDR) drives formation of chromatin condensates enriched in heterochromatin marks through electrostatic interactions and bridging-induced phase separation; TRIP12-mediated condensate formation alters cell cycle progression, genome accessibility, and transcription independently of its ubiquitin ligase activity. Overexpression of IDR deletion mutants, live-cell imaging, FRAP, ATAC-seq, RNA-seq, biophysical condensate assays iScience Medium 41660270
2023 Ku70 phosphorylation at S155 enhances association with TRIP12; co-immunoprecipitation showed increased TRIP12–Ku70 interaction upon ionizing radiation treatment, suggesting TRIP12 associates with Ku70 in a DNA-damage-dependent manner. BioID2 proximity labeling, proximity ligation assay, co-immunoprecipitation with ionizing radiation treatment International journal of molecular sciences Low 37108203
2024 TRIP12 is required for pancreatic acinar-to-ductal metaplasia (ADM) and KrasG12D-induced preneoplastic lesion formation in vivo; loss of TRIP12 prevents ADM after pancreatic injury and impairs metastasis in KrasG12D/Trp53R172H mice, while TRIP12 overexpression is required for PDAC cell growth and E2F target gene expression. Genetically modified mouse models (conditional KO, KrasG12D/Trp53R172H), ex vivo acinar explants, PDAC cell lines, western blotting The Journal of pathology Medium 38924548

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. Cell 300 22884692
2020 The Ubiquitin Ligase TRIP12 Limits PARP1 Trapping and Constrains PARP Inhibitor Efficiency. Cell reports 105 32755579
2021 Tryptophan potentiates CD8+ T cells against cancer cells by TRIP12 tryptophanylation and surface PD-1 downregulation. Journal for immunotherapy of cancer 92 34326168
2021 TRIP12 promotes small-molecule-induced degradation through K29/K48-branched ubiquitin chains. Molecular cell 80 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 47 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 43 28251352
2016 Trip12 is an E3 ubiquitin ligase for USP7/HAUSP involved in the DNA damage response. FEBS letters 43 27800609
2016 TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects. Oncogene 42 27425591
2021 TRIP12 ubiquitination of glucocerebrosidase contributes to neurodegeneration in Parkinson's disease. Neuron 39 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
2020 Mild iron overload induces TRIP12-mediated degradation of YY1 to trigger hepatic inflammation. Free radical biology & medicine 28 33080340
2021 Proteasomal degradation of the tumour suppressor FBW7 requires branched ubiquitylation by TRIP12. Nature communications 27 33824312
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
2023 The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant. European journal of human genetics : EJHG 17 36747006
2010 The TRIP from ULF to ARF. Cancer cell 16 20385357
2024 circEPB41L2 blocks the progression and metastasis in non-small cell lung cancer by promoting TRIP12-triggered PTBP1 ubiquitylation. Cell death discovery 14 38341427
2022 Episignature Mapping of TRIP12 Provides Functional Insight into Clark-Baraitser Syndrome. International journal of molecular sciences 13 36430143
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
2025 TRIP12's role in the governance of DNA polymerase β involvement in DNA damage response and repair. Nucleic acids research 9 40613707
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
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
2025 Helicobacter pylori activates DOPEY1 to promote p53 degradation through the USP7/TRIP12 axis in gastric tumorigenesis. Oncogene 5 39939725
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
2025 Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12. Cell reports 4 40928944
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
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
2025 The TRIP12 E3 ligase induces SWI/SNF component BRG1-β-catenin interaction to promote Wnt signaling. Nature communications 1 40473626
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
2026 TRIP12 promotes HIV-1 replication and latency reactivation by stabilizing Tat via USP7-mediated deubiquitination. Journal of virology 0 42126234
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 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

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