Affinage

TRIP13

Pachytene checkpoint protein 2 homolog · UniProt Q15645

Length
432 aa
Mass
48.6 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIP13 is a hexameric AAA+ ATPase that functions as a universal remodeler of HORMA-domain proteins, coupling ATP-driven translocation to conformational conversion of its clients from a signaling-active 'closed' state to an inactive 'open' state (PMID:25918846, PMID:29973720). Working with the adapter p31(comet), TRIP13 engages the disordered N-terminus of closed-conformation MAD2 through its axial pore loops and locally unfolds the MAD2 C-terminal αA helix, dissociating MAD2 from its partners; this remodeling disassembles the mitotic checkpoint complex and silences the spindle assembly checkpoint to permit anaphase onset, a reaction reconstituted from purified components and visualized by crystal and cryo-EM structures of the remodeling complex (PMID:25918846, PMID:25092294, PMID:29208896, PMID:29973720). The same N-terminal engagement mechanism is conserved across HORMA clients: TRIP13 removes meiotic HORMAD1/HORMAD2 from synapsed chromosome axes and is required for synaptonemal complex formation, recombination progression after strand invasion, and crossover control during mouse meiosis (PMID:19851446, PMID:17696610, PMID:20711356, PMID:28659378, PMID:39207914). Beyond mitosis and meiosis, TRIP13 disassembles the REV7(MAD2L2)-Shieldin and REV7-REV3/Pol-ζ complexes by the analogous closed-to-open conversion of REV7, shifting DNA repair toward homologous recombination and away from error-prone end-joining and translesion synthesis (PMID:31915374, PMID:33597306). Its catalytic activity additionally supports HR-mediated tolerance of oncogene-induced replication stress in KRAS-mutant cells (PMID:40115747). Biallelic loss-of-function TRIP13 mutations impair the spindle assembly checkpoint and cause chromosome missegregation in patient cells, with rescue upon TRIP13 reintroduction (PMID:28553959). In cancer contexts, TRIP13 acts through additional partners—enhancing USP7-substrate deubiquitination to stabilize oncoproteins (PMID:34061780), and stabilizing or activating partners including HAT1, DDX21, ACTN4, and YWHAE to drive proliferative signaling (PMID:31533816, PMID:41535263, PMID:39187490, PMID:38012658); it is also subject to EGFR-mediated Y56 phosphorylation that enhances NHEJ and radioresistance (PMID:34111559).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2007 High

    Established that TRIP13 acts in meiotic recombination downstream of DSB formation and strand invasion, defining its first in vivo functional role.

    Evidence Knockout mouse spermatocytes with recombination-marker immunofluorescence and double-mutant epistasis

    PMID:17696610

    Open questions at the time
    • Molecular activity behind the recombination defect not defined at this stage
    • No biochemical mechanism linking TRIP13 to recombination intermediate resolution
  2. 2009 High

    Identified HORMAD1/HORMAD2 as in vivo TRIP13-dependent factors whose removal from synapsed axes requires TRIP13, hinting at a HORMA-protein-directed activity.

    Evidence Knockout/hypomorph mouse model with HORMAD immunofluorescence on meiotic chromosomes

    PMID:19851446

    Open questions at the time
    • Whether TRIP13 acts directly on HORMADs vs indirectly was unresolved
    • No biochemical demonstration of conformational remodeling
  3. 2010 High

    Defined the breadth of meiotic phenotypes (synapsis, sex body, crossover number/distribution) using graded alleles, establishing TRIP13 dosage sensitivity in meiotic chromosome biology.

    Evidence Multiple hypomorphic alleles analyzed by cytology and chiasma counting

    PMID:20711356

    Open questions at the time
    • Mechanistic link between molecular activity and synapsis/crossover phenotypes not established
  4. 2014 High

    Established the mitotic function of TRIP13 as a kinetochore-localized, ATPase-dependent silencer of the spindle assembly checkpoint that disassembles the MCC with p31(comet), reconstituted from purified components.

    Evidence Immunofluorescence localization, siRNA knockdown with mitotic timing, ATPase-dead rescue, and in vitro MCC disassembly assays with APC/C readout

    PMID:25012665 PMID:25092294

    Open questions at the time
    • Atomic mechanism of MAD2 remodeling not yet resolved
    • How substrate is selected at the kinetochore not defined
  5. 2014 Medium

    Linked TRIP13 to DNA double-strand break repair pathway choice, showing it binds DNA-PKcs complex proteins and promotes NHEJ and treatment resistance.

    Evidence Mass spectrometry of binding partners and NHEJ reporter assays with over/knockdown in cancer cells

    PMID:25078033

    Open questions at the time
    • Direct substrate of remodeling in repair not identified at this point
    • Single lab, mechanism of NHEJ promotion inferred
  6. 2015 High

    Defined TRIP13 as an AAA+ protein-remodeling ATPase that converts closed MAD2 to open MAD2 via p31(comet), unifying its mitotic and meiotic roles around HORMA conformational conversion.

    Evidence Crystal structure of C. elegans PCH-2 and in vitro MAD2 conversion assay with p31(comet)

    PMID:25918846

    Open questions at the time
    • Structure of the human enzyme-substrate complex not yet solved
    • Precise coupling of ATP hydrolysis to unfolding undefined
  7. 2015 High

    Mapped the bipartite substrate-binding architecture, showing oligomeric TRIP13 requires simultaneous p31(comet) and C-MAD2-complex occupancy for high-affinity engagement.

    Evidence Recombinant binding assays and reciprocal co-IP of TRIP13 with p31(comet) and MCC

    PMID:26324890

    Open questions at the time
    • Dynamics of substrate handoff during catalysis not resolved
  8. 2017 High

    Resolved the human enzyme structure and the molecular mechanism of MAD2 remodeling, showing local C-terminal unfolding and identifying the conserved N-terminal engagement of HORMA clients shared between MAD2 and meiotic HORMAD1.

    Evidence Human TRIP13 crystal structure, NMR of MAD2, crosslinking MS, truncation-mutant remodeling assays, and spermatocyte immunofluorescence

    PMID:28659378 PMID:29208896

    Open questions at the time
    • Full translocation trajectory not yet visualized structurally
  9. 2017 High

    Connected TRIP13 to human disease, demonstrating that biallelic loss-of-function impairs the SAC and causes chromosome missegregation, rescuable by TRIP13 reintroduction.

    Evidence Patient-derived cells with SAC and segregation assays and rescue

    PMID:28553959

    Open questions at the time
    • Genotype-phenotype range across tissues not fully mapped
  10. 2018 High

    Visualized the complete remodeling complex and established that TRIP13 has a dual role—maintaining the open-MAD2 pool for checkpoint activation and disassembling MCC for mitotic exit.

    Evidence Cryo-EM of TRIP13-p31comet-C-MAD2-CDC20 plus degron depletion with APC15 double-depletion mitotic exit assays

    PMID:29973720 PMID:30341343

    Open questions at the time
    • How the same enzyme is biased toward assembly vs disassembly in vivo not fully defined
  11. 2020 High

    Extended TRIP13's HORMA-remodeling activity to REV7, showing it disassembles REV7-Shieldin and REV7-REV3/Pol-ζ complexes to favor homologous recombination over end-joining and translesion synthesis.

    Evidence REV7 conformational assays, co-IP, HR reporters, and PARP inhibitor sensitivity in BRCA1-deficient cells; p31(comet)-dependence shown by co-IP and chromatin fractionation

    PMID:31915374 PMID:33051298

    Open questions at the time
    • In vivo balance between repair-pathway choices across tissues unresolved
    • p31(comet) role in REV7 extraction shown in a single lab
  12. 2021 High

    Provided structural mechanism for Shieldin disassembly, showing REV7 N-terminal insertion into the TRIP13 channel and ATP-hydrolysis-driven rotatory disassembly, and defined REV7 dimerization as a prerequisite for TRIP13 engagement.

    Evidence Crystal and cryo-EM structures of Shieldin sub-complexes with TRIP13 plus co-IP with dimerization-defective MAD2L2 mutants and NHEJ reporters

    PMID:33597306 PMID:34521823

    Open questions at the time
    • Single co-IP-based confidence for dimerization requirement (medium evidence)
  13. 2021 Medium

    Uncovered a non-HORMA, deubiquitination-promoting function in cancer, with TRIP13 enhancing USP7-substrate association to protect oncoproteins and drive tumorigenesis.

    Evidence Co-IP with USP7, ubiquitination assays, transgenic mouse tumor model, and USP7-inhibitor rescue

    PMID:34061780

    Open questions at the time
    • Whether ATPase activity is required for the USP7 effect not established here
    • Single lab
  14. 2022 Medium

    Placed TRIP13 in immediate-early DNA damage sensing, linking it to MRE11/MRN, MDC1 recruitment, and ATM signaling amplification.

    Evidence Proximity-labeling proteomics, co-IP with MRE11, MDC1 recruitment imaging, and ATM signaling western blot

    PMID:36552858

    Open questions at the time
    • Direct vs indirect MRE11 interaction not fully resolved
    • Single lab
  15. 2024 High

    Refined TRIP13 meiotic localization to the synaptonemal complex and telomeres, independent of axial element proteins, and confirmed dosage sensitivity for HORMAD removal and asynapsis phenotypes.

    Evidence FLAG-tagged knock-in mouse live imaging and immunofluorescence with null/heterozygous genetic analysis

    PMID:39207914

    Open questions at the time
    • Recruitment determinants to SC and telomeres not identified
  16. 2025 Medium

    Demonstrated that TRIP13's HR-supporting activity confers tolerance to oncogene-induced replication stress, rationalizing its cancer dependency.

    Evidence Genetic and pharmacological TRIP13 depletion in KRASG12V cells with HR-deficiency phenotype assays

    PMID:40115747

    Open questions at the time
    • Mechanistic link between HORMA remodeling and replication-stress tolerance not fully traced
    • Single lab
  17. 2025 Medium

    Characterized regulation of TRIP13 protein stability and transcription in cancer, identifying HSPA9-USP1 stabilization and STAT3 feedback control.

    Evidence Co-IP of HSPA9/USP1/TRIP13 complex with domain mapping and ubiquitination assays; STAT3 ChIP at TRIP13 promoter with rescue and xenograft

    PMID:39939802 PMID:40140922

    Open questions at the time
    • Generality of these regulatory circuits beyond myeloma/TNBC unknown
    • Single lab each

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIP13's canonical HORMA-remodeling ATPase activity mechanistically relates to its diverse cancer partner interactions (ACTN4, FGFR4, LRP6, YWHAE, HAT1, DDX21, USP7) remains unresolved.
  • Whether non-HORMA partner effects require ATPase/remodeling activity is not consistently tested
  • Most oncogenic partner interactions rest on single-lab co-IP evidence
  • Direct vs indirect nature of several partner interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0140657 ATP-dependent activity 5 GO:0098772 molecular function regulator activity 4 GO:0016787 hydrolase activity 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-1474165 Reproduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3
Partners
DDX21HAT1MAD2MRE11P31(COMET)/MAD2L1BPREV7/MAD2L2USP7YWHAE
Complex memberships
HSPA9-USP1-TRIP13 complexREV7-Shieldin (as remodeling substrate)TRIP13-p31(comet)-C-MAD2-CDC20 remodeling complexmitotic checkpoint complex (MCC, as remodeling substrate)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 TRIP13 is required for depletion of HORMAD1 and HORMAD2 from synapsed chromosome axes during meiosis; loss of TRIP13 results in abnormal persistence of HORMADs on synapsed chromosomes and disrupts mutually exclusive HORMAD-rich and synapsed chromatin domains. Genetic knockout/hypomorph mouse model with immunofluorescence analysis of HORMAD1/HORMAD2 localization on meiotic chromosomes PLoS genetics High 19851446
2007 Mouse TRIP13 is required for completing a subset of meiotic recombination events after strand invasion; TRIP13-deficient spermatocytes retain recombination intermediates (RAD51, BLM, RPA) despite full synapsis. Epistasis analysis showed SPO11, MEI1, REC8, and DMC1 are epistatic to TRIP13, placing TRIP13 downstream of these recombination factors. Genetic knockout mouse model with immunofluorescence for recombination markers; double-mutant epistasis analysis PLoS genetics High 17696610
2010 TRIP13 is required for proper synaptonemal complex formation, efficient synapsis of sex chromosomes, sex body formation, normal crossover numbers and distribution, and early recombination steps after DSB formation in mouse meiosis. Distinct Trip13 alleles (moderate and severe hypomorphs) analyzed by cytology, immunofluorescence, chiasma counting PLoS genetics High 20711356
2015 TRIP13 is a protein-remodeling AAA+ ATPase that, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from its signaling-active 'closed' conformer to an inactive 'open' conformer, thereby inactivating the spindle assembly checkpoint and disassembling mitotic checkpoint complexes. The substrate-recognition domain of TRIP13 is related to those of NSF and p97. Crystal structure of C. elegans PCH-2; in vitro MAD2 conformational conversion assay with TRIP13 and p31(comet) eLife High 25918846
2014 TRIP13 binds to DNA-PKcs complex proteins that mediate nonhomologous end joining (NHEJ) and promotes NHEJ repair even when homologous recombination is intact; overexpression of TRIP13 enhances NHEJ-mediated DNA repair and promotes treatment resistance. Mass spectrometry identification of TRIP13-binding partners; NHEJ reporter assays; overexpression and knockdown in cancer cells Nature communications Medium 25078033
2014 Endogenous TRIP13 localizes to kinetochores in mitosis. TRIP13 knockdown delays metaphase-to-anaphase transition by prolonging the presence of the mitotic checkpoint complex (MCC) and its inhibition of APC/C. The ATPase activity of TRIP13 is essential for this checkpoint-silencing function, and TRIP13 is required for p31(comet)-mediated mitotic checkpoint silencing. Immunofluorescence localization; siRNA knockdown with mitotic timing assays; ATPase-dead mutant rescue experiments The Journal of biological chemistry High 25012665
2014 TRIP13 AAA-ATPase, acting jointly with p31(comet), promotes ATP-dependent disassembly of the Cdc20-Mad2 subcomplex and the full mitotic checkpoint complex (MCC), releasing Mad2 from MCC and abrogating checkpoint inhibition of APC/C. TRIP13 was identified as the factor in HeLa extracts responsible for ATP- and p31(comet)-dependent MCC disassembly. Biochemical fractionation of HeLa extracts; in vitro MCC disassembly assay with recombinant TRIP13 and p31(comet); APC/C activity assay Proceedings of the National Academy of Sciences of the United States of America High 25092294
2015 The oligomeric form of TRIP13 binds both p31(comet) and MCC. p31(comet) and checkpoint complexes mutually promote each other's binding to oligomeric TRIP13; the substrate-binding site of TRIP13 comprises subsites specific for p31(comet) and the C-Mad2-containing complex, and simultaneous occupancy of both subsites is required for high-affinity binding. Binding assays with recombinant proteins; co-immunoprecipitation of TRIP13 with p31(comet) and MCC components Proceedings of the National Academy of Sciences of the United States of America High 26324890
2017 TRIP13 and p31(comet) catalyze the conversion of C-Mad2 to O-Mad2 by locally unfolding the Mad2 C-terminal region without disrupting its stably folded core; the crystal structure of human TRIP13 was determined and functional TRIP13 residues mediating p31(comet)-Mad2 binding and coupling ATP hydrolysis to local Mad2 unfolding were identified. TRIP13-p31(comet) intercepts and disassembles free MCC not bound to APC/C. NMR spectroscopy of MAD2 conformational change; crystal structure of human TRIP13; mutagenesis of functional residues; in vitro APC/C inhibition assays Nature communications High 29208896
2017 TRIP13 recognizes MAD2 through the adapter p31(comet), which binds the TRIP13 N-terminal domain to position the disordered MAD2 N-terminus for engagement by TRIP13 pore loops; TRIP13 then unfolds MAD2 in an ATP-dependent manner. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro and causes SAC defects in cells. Similar truncation of HORMAD1 in spermatocytes impairs TRIP13-mediated removal from meiotic chromosomes, demonstrating a conserved N-terminal engagement mechanism. X-ray crystallography; crosslinking mass spectrometry; in vitro TRIP13 remodeling assay with truncation mutants; mouse spermatocyte immunofluorescence The EMBO journal High 28659378
2018 Cryo-EM structures of the TRIP13-p31(comet)-C-MAD2-CDC20 complex reveal that p31(comet) recruits C-MAD2 to a defined site on the TRIP13 hexameric ring, positioning the MAD2 N-terminus to insert into the axial pore. TRIP13 couples sequential ATP-driven translocation along MAD2 N-terminus to push and rotate the p31(comet)-C-MAD2 complex, unwinding the αA helix of C-MAD2 required to stabilize the closed β-sheet, thereby converting C-MAD2 to O-MAD2 and dissociating MAD2 from p31(comet). Cryo-electron microscopy structure determination of TRIP13-p31comet-C-MAD2-CDC20 complex; molecular modeling of translocation mechanism Nature High 29973720
2018 TRIP13 catalytic activity is required both to maintain a pool of open-state Mad2 for MCC assembly (supporting checkpoint activation) and for timely mitotic exit through catalytic disassembly of MCC. Combining TRIP13 depletion with elimination of APC15-dependent Cdc20 ubiquitination/degradation results in complete inability to exit mitosis even when kinetochore MCC assembly is prevented. Degron-tagging for rapid TRIP13 depletion; double depletion (TRIP13 + APC15) with mitotic exit assays; Mad2 conformer pool measurements Nature communications High 30341343
2020 TRIP13 ATPase catalyzes an inactivating conformational change of REV7 (MAD2L2) from its active 'closed' conformation to an inactive 'open' conformation, thereby dissociating the REV7-Shieldin complex and promoting homology-directed repair (HDR). TRIP13 similarly disassembles the REV7-REV3 translesion synthesis (TLS) complex, inhibiting error-prone replicative lesion bypass and interstrand crosslink repair. Conformational assays for REV7 closed/open states; co-IP of REV7-Shieldin complex; HR reporter assay; PARP inhibitor sensitivity assay in BRCA1-deficient cells Nature cell biology High 31915374
2020 p31(comet) binds to the REV7-Shieldin complex in cells, mediates TRIP13-REV7 interaction, promotes REV7 inactivation and dissociation from Shieldin subunit SHLD3, and participates in extraction of REV7 from chromatin. p31(comet) also releases REV7 from the REV3/Pol-ζ complex, counteracting TLS. Co-IP of p31(comet) with REV7-Shieldin; chromatin fractionation; PARP inhibitor resistance assay Proceedings of the National Academy of Sciences of the United States of America Medium 33051298
2021 Crystal structures of human SHLD3-REV7 binary and fused SHLD2-SHLD3-REV7 ternary complexes show that Shieldin assembly requires SHLD2-SHLD3-induced conformational heterodimerization of O-REV7 and C-REV7. Cryo-EM structures of ATPγS-bound SHLD2-SHLD3-REV7-TRIP13 complexes show that the N-terminus of REV7 inserts into the TRIP13 central channel; the safety-belt segment of C-REV7 contacts a conserved negatively charged TRIP13 loop, and ATP hydrolysis-triggered rotatory motions drive disassembly of the Shieldin complex. X-ray crystallography of Shieldin sub-complexes; cryo-EM of TRIP13-Shieldin complex; functional disassembly assays Proceedings of the National Academy of Sciences of the United States of America High 33597306
2021 MAD2L2 (REV7) dimerization is required for appropriate shieldin function in NHEJ; dimerization is mediated by SHLD2 and accelerates MAD2L2-SHLD3 interaction. MAD2L2 dimerization combined with SHLD3 presence is required for shieldin interaction with TRIP13 ATPase. Appropriate TRIP13 levels are important for proper shieldin (dis)assembly and activity in DNA repair. Co-IP of shieldin components; dimerization-defective MAD2L2 mutants; NHEJ reporter assay Nature communications Medium 34521823
2020 In C. elegans, PCH-2/TRIP13 controls spindle checkpoint strength by regulating the availability of inactive (open-state) Mad2 at and near unattached kinetochores; this function is required in large cells (germline precursor cells) and depends on CMT-1 (p31(comet) ortholog) for PCH-2 localization to unattached kinetochores and its enrichment in germline precursor cells. C. elegans genetic manipulation of cell volume; PCH-2 localization by immunofluorescence; spindle checkpoint strength assays; genetic epistasis with cmt-1 Molecular biology of the cell Medium 32697629
2017 Biallelic loss-of-function mutations in TRIP13 cause substantial impairment of the spindle assembly checkpoint (SAC), leading to a high rate of chromosome missegregation; restoring TRIP13 function rescues accurate segregation and SAC proficiency in patient cells. Patient-derived cell lines with TRIP13 mutations; SAC functional assays; chromosome segregation assays; rescue by TRIP13 reintroduction Nature genetics High 28553959
2017 TRIP13 overexpression significantly reduces, and TRIP13 reduction exacerbates, the mitotic delay associated with Mad2 overexpression (but not microtubule depolymerization-induced delay). Combination of Mad2 overexpression and TRIP13 loss reduces ability of checkpoint complexes to disassemble. TRIP13 overexpression and knockdown in Mad2-overexpressing cells; mitotic timing; MCC disassembly assays; xenograft proliferation Cell reports Medium 28564602
2021 TRIP13 increases cellular deubiquitination by enhancing the association of the deubiquitinase USP7 with its substrates (NEK2, PTEN, p53), thereby protecting oncogenic proteins from ubiquitin-mediated degradation; this activity promotes B cell tumor development in transgenic mice. TRIP13-induced resistance to proteasome inhibition can be overcome by a USP7 inhibitor. Co-IP of TRIP13 with USP7; ubiquitination assays; TRIP13 transgenic mouse tumor model; in vitro and in vivo USP7 inhibitor rescue The Journal of clinical investigation Medium 34061780
2019 TRIP13 interacts with ACTN4 and positively regulates ACTN4 expression, thereby activating the AKT/mTOR pathway to promote hepatocellular carcinoma progression. Co-IP of TRIP13 with ACTN4; gain- and loss-of-function studies; AKT/mTOR pathway western blotting; xenograft models Journal of experimental & clinical cancer research : CR Medium 31533816
2019 TRIP13 promotes glioblastoma cell proliferation, migration, and invasion by suppressing FBXW7 transcription (by directly binding to the FBXW7 promoter region), thereby stabilizing c-MYC protein levels. ChIP/promoter binding assay for TRIP13 at FBXW7 promoter; western blot for c-MYC; gain- and loss-of-function in GBM cells British journal of cancer Medium 31740732
2017 TRIP13 directly interacts with Tetratricopeptide Repeat Domain 5 (TTC5), a p53 co-factor; knockdown of TRIP13 in tubular epithelial cells in the presence of oxidative stress increased p53 activity at Serine 15, linking TRIP13 to suppression of p53-mediated apoptosis. Co-IP of TRIP13 with TTC5; TRIP13 hypomorph mice with ischemia-reperfusion injury; p53-Ser15 phosphorylation assay after TRIP13 knockdown Scientific reports Medium 28256593
2022 TRIP13 participates in immediate-early DNA damage sensing: it is recruited to DNA damage sites within seconds after damage, interacts with MRE11 (identified by quantitative proximity-labeling proteomics), controls MDC1 recruitment to damage sites by regulating MDC1-MRN complex interaction, and is involved in ATM signaling amplification. Proximity-labeling quantitative proteomics (BioID); co-IP of TRIP13 with MRE11; MDC1 recruitment assay by immunofluorescence; ATM signaling western blot Cells Medium 36552858
2021 TRIP13 phosphorylation at tyrosine 56 (Y56) by EGFR promotes NHEJ repair and induces radiation resistance in head and neck cancer; suppression of Y56 phosphorylation abrogates these effects. Phospho-site identification; EGFR inhibition and TRIP13-Y56 mutant functional studies; NHEJ reporter; radiation survival assay Molecular therapy : the journal of the American Society of Gene Therapy Medium 34111559
2024 TRIP13 localizes to the synaptonemal complex (SC) of synapsed chromosomes in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. This localization is independent of SC axial element proteins REC8, SYCP2, and SYCP3. TRIP13 is a dosage-sensitive regulator: heterozygous Trip13 mice show meiotic defects less severe than nulls. Loss of TRIP13 causes persistence of HORMAD1 and HORMAD2 on synapsed SC and chromosome asynapsis preferentially affecting XY and centromeric ends. Live imaging and immunofluorescence of FLAG-tagged TRIP13 knock-in mice; genetic analysis of Trip13 null and heterozygous mice; chromosome spread analysis eLife High 39207914
2022 TRIP13 interacts with FGFR4 in colorectal cancer cells; this interaction is required for activation of the EGFR-AKT pathway. TRIP13 also participates in WNT signaling regulation and EMT in colorectal cancer. Co-IP of TRIP13 with FGFR4; pathway western blotting; TRIP13 KD xenograft and metastasis assays Molecular oncology Low 33037736
2020 TRIP13 interacts with LRP6 (co-localization and co-immunoprecipitation in lung cancer cells) and promotes activation of the Wnt/β-catenin signaling pathway, driving proliferation and invasion. Co-IP and confocal immunofluorescence co-localization of TRIP13 with LRP6; β-catenin activation western blot; colony formation and invasion assays Journal of molecular histology Low 33128167
2021 TRIP13 directly interacts with HAT1; this interaction inhibits UBE4A-mediated ubiquitination degradation of HAT1, stabilizing HAT1 protein. TRIP13's ATPase activity is required for HAT1 binding, and through HAT1 stabilization TRIP13 promotes Foxp3 expression and Treg expansion downstream of TNF-TNFR2 signaling. Co-IP of TRIP13 with HAT1 and UBE4A; ubiquitination assay; ATPase-dead TRIP13 mutant; TRIP13 KO mouse colitis model Cell death & disease Medium 41535263
2023 TRIP13 directly interacts with DDX21 and stabilizes DDX21 expression by restraining its ubiquitination-dependent degradation, thereby promoting gastric cancer progression. HDAC1 acts as an upstream transcriptional activator of TRIP13 by targeting the TRIP13 promoter region. Co-IP of TRIP13 with DDX21; ubiquitination assay; ChIP of HDAC1 at TRIP13 promoter; gain- and loss-of-function in gastric cancer cells Cell death & disease Medium 39187490
2024 THC (tetrahydrocurcumin) directly targets TRIP13 (confirmed by click chemistry target fishing, CETSA, DARTS, and SPR). In TNBC cells, TRIP13 forms a trimeric complex with USP7 and c-FLIP. THC disrupts this TRIP13/USP7/c-FLIP complex, leading to ubiquitination and degradation of c-FLIP and extrinsic apoptosis. Click chemistry target fishing; CETSA; DARTS; SPR; co-IP of TRIP13/USP7/c-FLIP complex; in vitro deubiquitination assay; confocal microscopy Journal of advanced research Medium 39505147
2023 DCZ5417 inhibits TRIP13 ATPase activity and disrupts the TRIP13/YWHAE protein complex, thereby suppressing ERK/MAPK signaling and inhibiting multiple myeloma cell proliferation. Molecular docking; pull-down; surface plasmon resonance; cellular thermal shift assay; ATPase activity assay; co-IP of TRIP13 with YWHAE; ERK/MAPK western blot; xenograft Journal of translational medicine Medium 38012658
2025 In KRAS-mutant pancreatic cancer cells, TRIP13 promotes survival specifically in a homologous recombination-dependent manner; TRIP13-depleted KRASG12V-expressing cells acquire HR-deficiency phenotypes (sensitivity to TLS inhibitors and PARP inhibitors), indicating TRIP13 supports HR-mediated tolerance of oncogene-induced replication stress. Genetic (siRNA/CRISPR) and pharmacological TRIP13 depletion in KRASG12V-expressing HPNE cells; DNA synthesis assays; HR-deficiency phenotype assays (TLS and PARP inhibitor sensitivity) NAR cancer Medium 40115747
2025 TRIP13 promotes TNBC cell viability and migration by activating STAT3 signaling; STAT3 in turn binds a STAT3-recognition element in the TRIP13 regulatory region to upregulate TRIP13, forming a positive TRIP13/STAT3 feedback circuit. Western blot for STAT3 activation; ChIP of STAT3 at TRIP13 promoter; TRIP13 overexpression rescue of bardoxolone-induced apoptosis; in vivo xenograft Acta pharmacologica Sinica Medium 39939802
2025 HSPA9 (exosomal) stabilizes TRIP13 protein by recruiting the deubiquitinase USP1 to TRIP13 via the carboxyl-terminal peptide-binding domain of HSPA9, thereby preventing TRIP13 ubiquitination and degradation; the HSPA9-USP1-TRIP13 complex is stable in the cytoplasm and its integrity promotes bortezomib resistance in multiple myeloma. Co-IP of HSPA9/USP1/TRIP13 complex; protein truncation test to map HSPA9-USP1 interaction domain; ubiquitination assay; immunofluorescence co-localization; xenograft Cell communication and signaling : CCS Medium 40140922

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLoS genetics 333 19851446
2007 Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis. PLoS genetics 177 17696610
2010 Mouse TRIP13/PCH2 is required for recombination and normal higher-order chromosome structure during meiosis. PLoS genetics 161 20711356
2015 TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching. eLife 143 25918846
2014 TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer. Nature communications 131 25078033
2020 TRIP13 regulates DNA repair pathway choice through REV7 conformational change. Nature cell biology 129 31915374
2020 HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity. Molecular cell 129 31932165
2014 Thyroid hormone receptor interacting protein 13 (TRIP13) AAA-ATPase is a novel mitotic checkpoint-silencing protein. The Journal of biological chemistry 124 25012665
2017 Biallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation. Nature genetics 119 28553959
2018 Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. Nature 111 29973720
2014 Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31(comet). Proceedings of the National Academy of Sciences of the United States of America 108 25092294
2020 Bi-allelic Missense Pathogenic Variants in TRIP13 Cause Female Infertility Characterized by Oocyte Maturation Arrest. American journal of human genetics 102 32473092
2015 Pch2(TRIP13): controlling cell division through regulation of HORMA domains. Chromosoma 78 25895724
2017 The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding. The EMBO journal 71 28659378
2019 MiR-515-5p acts as a tumor suppressor via targeting TRIP13 in prostate cancer. International journal of biological macromolecules 65 30685303
2015 Mode of interaction of TRIP13 AAA-ATPase with the Mad2-binding protein p31comet and with mitotic checkpoint complexes. Proceedings of the National Academy of Sciences of the United States of America 64 26324890
2019 Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4. Journal of experimental & clinical cancer research : CR 63 31533816
2019 Insights into a Crucial Role of TRIP13 in Human Cancer. Computational and structural biotechnology journal 61 31321001
2019 TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis. British journal of cancer 61 31740732
2021 HMGA1-TRIP13 axis promotes stemness and epithelial mesenchymal transition of perihilar cholangiocarcinoma in a positive feedback loop dependent on c-Myc. Journal of experimental & clinical cancer research : CR 49 33648560
2018 Silencing TRIP13 inhibits cell growth and metastasis of hepatocellular carcinoma by activating of TGF-β1/smad3. Cancer cell international 47 30564064
2020 TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status. Molecular oncology 45 33037736
2018 TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC. Nature communications 45 30341343
2022 DCZ0415, a small-molecule inhibitor targeting TRIP13, inhibits EMT and metastasis via inactivation of the FGFR4/STAT3 axis and the Wnt/β-catenin pathway in colorectal cancer. Molecular oncology 44 35194944
2017 Mad2 Overexpression Uncovers a Critical Role for TRIP13 in Mitotic Exit. Cell reports 42 28564602
2021 TRIP13 modulates protein deubiquitination and accelerates tumor development and progression of B cell malignancies. The Journal of clinical investigation 36 34061780
2017 Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing. Nature communications 36 29208896
2016 TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion. Oncology letters 36 28105232
2021 MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair. Nature communications 34 34521823
2020 p31comet promotes homologous recombination by inactivating REV7 through the TRIP13 ATPase. Proceedings of the National Academy of Sciences of the United States of America 30 33051298
2022 Trip13 Depletion in Liver Cancer Induces a Lipogenic Response Contributing to Plin2-Dependent Mitotic Cell Death. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 36031387
2019 Elevated TRIP13 drives cell proliferation and drug resistance in bladder cancer. American journal of translational research 28 31396344
2019 Increased expression of TRIP13 drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway. International journal of biological sciences 27 31337978
2021 TRIP13 promotes lung cancer cell growth and metastasis through AKT/mTORC1/c-Myc signaling. Cancer biomarkers : section A of Disease markers 25 33136091
2022 Evaluation of the TRIP13 level in breast cancer and insights into potential molecular pathways. Journal of cellular and molecular medicine 24 35322916
2021 Hsa_circRNA_100146 Promotes Prostate Cancer Progression by Upregulating TRIP13 via Sponging miR-615-5p. Frontiers in molecular biosciences 24 34307457
2019 TRIP13 promotes proliferation and invasion of epithelial ovarian cancer cells through Notch signaling pathway. European review for medical and pharmacological sciences 24 30720159
2021 Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex. Proceedings of the National Academy of Sciences of the United States of America 22 33597306
2023 Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells. Cell death discovery 21 37669963
2021 Upregulation of TRIP13 promotes the malignant progression of lung cancer via the EMT pathway. Oncology reports 20 34184074
2020 TRIP13 promotes the proliferation and invasion of lung cancer cells via the Wnt signaling pathway and epithelial-mesenchymal transition. Journal of molecular histology 20 33128167
2021 Phosphorylation of TRIP13 at Y56 induces radiation resistance but sensitizes head and neck cancer to cetuximab. Molecular therapy : the journal of the American Society of Gene Therapy 19 34111559
2020 Long non-coding RNA NORAD exhaustion represses prostate cancer progression through inhibiting TRIP13 expression via competitively binding to miR-495-3p. Cancer cell international 19 32694945
2017 TRIP13-deficient tubular epithelial cells are susceptible to apoptosis following acute kidney injury. Scientific reports 19 28256593
2023 TRIP13 overexpression promotes gefitinib resistance in non‑small cell lung cancer via regulating autophagy and phosphorylation of the EGFR signaling pathway. Oncology reports 17 36896765
2022 TRIP13, identified as a hub gene of tumor progression, is the target of microRNA-4693-5p and a potential therapeutic target for colorectal cancer. Cell death discovery 17 35075117
2021 TRIP13 exerts a cancer-promoting role in cervical cancer by enhancing Wnt/β-catenin signaling via ACTN4. Environmental toxicology 17 34061428
2024 TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis. eLife 16 39207914
2022 KIF18B promotes breast cancer cell proliferation, migration and invasion by targeting TRIP13 and activating the Wnt/β-catenin signaling pathway. Oncology letters 16 35251343
2022 Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 16 35972731
2023 Targeting of oncogenic AAA-ATPase TRIP13 reduces progression of pancreatic ductal adenocarcinoma. Neoplasia (New York, N.Y.) 15 38039923
2019 TRIP13 interference inhibits the proliferation and metastasis of thyroid cancer cells through regulating TTC5/p53 pathway and epithelial-mesenchymal transition related genes expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 31648166
2020 CETSA MS Profiling for a Comparative Assessment of FDA-Approved Antivirals Repurposed for COVID-19 Therapy Identifies TRIP13 as a Remdesivir Off-Target. SLAS discovery : advancing life sciences R & D 14 33208020
2022 TRIP13 knockdown inhibits the proliferation, migration, invasion, and promotes apoptosis by suppressing PI3K/AKT signaling pathway in U2OS cells. Molecular biology reports 12 35032258
2024 Tetrahydrocurcumin targets TRIP13 inhibiting the interaction of TRIP13/USP7/c-FLIP to mediate c-FLIP ubiquitination in triple-negative breast cancer. Journal of advanced research 11 39505147
2023 The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13-MAPK-YWHAE signaling pathway. Journal of translational medicine 11 38012658
2021 Clinical Significance and Systematic Expression Analysis of the Thyroid Receptor Interacting Protein 13 (TRIP13) as Human Gliomas Biomarker. Cancers 11 34066132
2019 The oncogenic role of TRIP13 in regulating proliferation, invasion, and cell cycle checkpoint in NSCLC cells. International journal of clinical and experimental pathology 11 31934178
2022 Inducing Synergistic DNA Damage by TRIP13 and PARP1 Inhibitors Provides a Potential Treatment for Hepatocellular Carcinoma. Journal of Cancer 10 35517402
2022 TRIP13 Induces Nedaplatin Resistance in Esophageal Squamous Cell Carcinoma by Enhancing Repair of DNA Damage and Inhibiting Apoptosis. BioMed research international 10 35601150
2021 DNA damage is overcome by TRIP13 overexpression during cisplatin nephrotoxicity. JCI insight 10 34806647
2023 Oncogenic Targets Regulated by Tumor-Suppressive miR-30c-1-3p and miR-30c-2-3p: TRIP13 Facilitates Cancer Cell Aggressiveness in Breast Cancer. Cancers 9 37627217
2021 Getting there: understanding the chromosomal recruitment of the AAA+ ATPase Pch2/TRIP13 during meiosis. Current genetics 9 33712914
2020 The conserved AAA-ATPase PCH-2 TRIP13 regulates spindle checkpoint strength. Molecular biology of the cell 9 32697629
2024 Targeting TRIP13 in favorable histology Wilms tumor with nuclear export inhibitors synergizes with doxorubicin. Communications biology 8 38589567
2023 Targeting TRIP13 for overcoming anticancer drug resistance (Review). Oncology reports 8 37800638
2023 Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma. Cancers 8 38067275
2022 TRIP13/FLNA Complex Promotes Tumor Progression and Is Associated with Unfavorable Outcomes in Melanoma. Journal of oncology 8 36268276
2022 TRIP13 Participates in Immediate-Early Sensing of DNA Strand Breaks and ATM Signaling Amplification through MRE11. Cells 8 36552858
2020 Disassembly of the Shieldin Complex by TRIP13. Cell cycle (Georgetown, Tex.) 8 32420796
2024 TRIP13 Activates Glycolysis to Promote Cell Stemness and Strengthen Doxorubicin Resistance of Colorectal Cancer Cells. Current medicinal chemistry 7 38347785
2024 TRIP13 regulates progression of gastric cancer through stabilising the expression of DDX21. Cell death & disease 7 39187490
2023 Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo. Bioorganic & medicinal chemistry letters 7 38092072
2022 MiR-129-5p/TRIP13 affects malignant phenotypes of colorectal cancer cells. Histology and histopathology 7 35362548
2025 Bardoxolone displays potent activity against triple negative breast cancer by inhibiting the TRIP13/STAT3 circuit. Acta pharmacologica Sinica 6 39939802
2025 TRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stress. NAR cancer 6 40115747
2024 Lnc-LINC00511 promotes gastric cancer progression by regulating MiR-29c-3p/TRIP13 axis through AKT/mTOR pathway. International journal of biological macromolecules 6 39389496
2025 Exosome-transmitted HSPA9 facilitates bortezomib resistance by targeting TRIP13/USP1 signaling in multiple myeloma. Cell communication and signaling : CCS 5 40140922
2024 TRIP13: A promising cancer immunotherapy target. Cancer innovation 5 39398261
2023 TI17, a novel compound, exerts anti-MM activity by impairing Trip13 function of DSBs repair and enhancing DNA damage. Cancer medicine 5 37942576
2019 Correction to: Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4. Journal of experimental & clinical cancer research : CR 5 31666112
2024 Role of TRIP13 in human cancer development. Molecular biology reports 4 39436503
2023 An integrated computational biology approach defines the crucial role of TRIP13 in pancreatic cancer. Computational and structural biotechnology journal 4 38074464
2017 [Study on the expression of TRIP13 mRNA in chronic lymphocytic leukemia B lymphocyte and the molecular mechanism of TRIP13 mediated JVM-2 cell proliferation and apoptosis]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 4 28810332
2025 TRIP13-induced NUSAP1 upregulation promotes CcRCC progression through EMT and PI3K/AKT/mTOR pathway. Journal of translational medicine 3 40790482
2024 High expression of TRIP13 is associated with tumor progression in H. pylori infection induced gastric cancer. Mutation research 3 38492425
2024 Identification of a novel splicing variant of thyroid hormone receptor interaction protein 13 (TRIP13) in female infertility characterized by oocyte maturation arrest. Journal of assisted reproduction and genetics 3 39297991
2023 TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis. bioRxiv : the preprint server for biology 3 37808842
2025 Repeated ionizing radiation exposure induces TRIP13 expression, conferring radioresistance in lung cancer cells. Scientific reports 2 39762328
2024 TRIP13 Plays an Important Role in the Sensitivity of Leukemia Cell Response to Sulforaphane Therapy. ACS omega 2 38911763
2024 Genome-Wide Methylation Profiling of Peripheral T-Cell Lymphomas Identifies TRIP13 as a Critical Driver of Tumor Proliferation and Survival. Epigenomes 2 39189258
2024 Integrated multiomic analysis identifies TRIP13 as a mediator of alveolar epithelial type II cell dysfunction in idiopathic pulmonary fibrosis. Biochimica et biophysica acta. Molecular basis of disease 2 39547519
2023 Novel mutations in TRIP13 lead to female infertility with oocyte maturation arrest. Yi chuan = Hereditas 2 37340965
2026 TRIP13 promotes the expansion and immunosuppression of CD4+Foxp3+ regulatory T cells by sustaining HAT1 stability. Cell death & disease 1 41535263
2025 Discovery of novel antimyeloma agents targeting TRIP13 by molecular modeling and bioassay. RSC medicinal chemistry 1 40337305
2025 Ping-Chong-Jiang-Ni Formula effectively inhibits migration and invasion of endometriosis 12Z cell line via TRIP13. Journal of food and drug analysis 1 40592337
2024 [TRIP13 Enhances Radioresistance of Lung Adenocarcinoma Cells 
through the Homologous Recombination Pathway]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 1 38296621
2024 TRIP13 - a potential drug target in cancer pharmacotherapy. Bioorganic chemistry 1 39042962
2023 CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA genes expression in colorectal cancer patients: novel diagnostic biomarkers. European review for medical and pharmacological sciences 1 37750623
2021 [Regulation of TRIP13 on Proliferation and Apoptosis of B-Cell Lymphoma Cells and Its Mechanism]. Zhongguo shi yan xue ye xue za zhi 1 34627428

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