Affinage

TRIP13

Pachytene checkpoint protein 2 homolog · UniProt Q15645

Length
432 aa
Mass
48.6 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIP13 is a hexameric AAA+ ATPase that remodels HORMA-domain proteins by threading their disordered N-termini through its central pore, converting them from closed/active to open/inactive conformations, thereby controlling the spindle assembly checkpoint, DNA damage repair pathway choice, and meiotic chromosome dynamics. Using the adapter p31(comet), TRIP13 converts closed MAD2 (C-MAD2) to open MAD2 (O-MAD2), disassembling the Mitotic Checkpoint Complex (MCC) to silence the spindle assembly checkpoint and permit anaphase onset; this activity, together with APC15-dependent Cdc20 degradation, constitutes the two essential routes for mitotic exit (PMID:25918846, PMID:29973720, PMID:30341343). TRIP13 similarly converts closed REV7 to open REV7 via p31(comet), disassembling the REV7–Shieldin complex to promote homologous recombination over NHEJ and disassembling REV7–REV3 to suppress translesion synthesis (PMID:31915374, PMID:33597306). In meiosis, TRIP13 localizes to the synaptonemal complex and telomeres, where it removes HORMAD1/HORMAD2 from synapsed axes through the same N-terminal threading mechanism, establishing proper chromosome domain organization and enabling crossover formation; biallelic TRIP13 loss-of-function mutations in humans cause severe chromosome missegregation due to spindle assembly checkpoint impairment (PMID:19851446, PMID:39207914, PMID:28553959).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2007 High

    Establishing that TRIP13 functions in meiotic recombination downstream of strand invasion resolved its placement in the meiotic DSB repair pathway and revealed its requirement for completing recombination events.

    Evidence Trip13-null mouse spermatocytes with retained recombination markers; epistasis with Spo11, Dmc1, Mei1, Rec8

    PMID:17696610

    Open questions at the time
    • Molecular substrate of TRIP13 in meiosis unknown
    • Whether TRIP13 acts catalytically or structurally was unclear
  2. 2009 High

    Identifying HORMAD1/HORMAD2 as targets of TRIP13-dependent removal from synapsed axes established that TRIP13 remodels HORMA-domain proteins in vivo, linking its ATPase activity to chromosome domain organization during meiosis.

    Evidence Trip13 mutant mice; immunofluorescence showing persistent HORMADs on synapsed chromosomes

    PMID:19851446

    Open questions at the time
    • Biochemical mechanism of HORMAD removal not yet reconstituted
    • Whether TRIP13 acts directly on HORMADs or through intermediaries was unknown
  3. 2010 High

    Demonstrating graded meiotic phenotypes with different Trip13 alleles revealed that TRIP13 is required for synaptonemal complex integrity, sex chromosome synapsis, and normal crossover number/distribution, broadening its meiotic role beyond HORMAD removal.

    Evidence Multiple Trip13 hypomorph and severe alleles in mice; cytological analysis of SC, MLH1/MLH3 foci, chiasmata

    PMID:20711356

    Open questions at the time
    • How TRIP13 dosage translates to distinct meiotic outcomes was mechanistically unexplained
    • Whether TRIP13 acts on recombination intermediates directly remained open
  4. 2014 High

    Two independent groups demonstrated that TRIP13 and p31(comet) catalytically disassemble the MCC through ATP hydrolysis, establishing TRIP13 as a direct SAC-silencing enzyme and connecting its AAA+ ATPase activity to mitotic checkpoint control.

    Evidence In vitro MCC disassembly from HeLa extracts; biochemical fractionation identifying TRIP13; TRIP13 knockdown delaying anaphase; kinetochore immunofluorescence

    PMID:25012665 PMID:25092294

    Open questions at the time
    • Structural basis of TRIP13-MCC interaction unknown
    • Whether TRIP13 acts on free MCC vs. APC/C-bound MCC was unresolved
  5. 2015 High

    Cryo-EM of the TRIP13 ortholog PCH-2 and reconstituted MAD2 conformational conversion established that TRIP13 is a hexameric unfoldase resembling ClpX that converts C-MAD2 to O-MAD2 using p31(comet) as an adapter, providing the first structural and biochemical framework for its remodeling mechanism.

    Evidence Cryo-EM of C. elegans PCH-2; in vitro MAD2 conversion assay with purified human TRIP13 and p31(comet)

    PMID:25918846

    Open questions at the time
    • Human TRIP13 structure not yet determined
    • How the N-terminus of MAD2 is engaged was unknown
  6. 2017 High

    Crystal structures of human TRIP13 and crosslinking-MS/NMR studies revealed that TRIP13 engages the disordered MAD2 N-terminus through axial pore loops and causes local unfolding of the MAD2 C-terminal region without disrupting the folded core, defining the mechanism as N-terminal threading; the same mechanism was shown to operate on HORMAD1 in meiosis.

    Evidence X-ray crystallography of human TRIP13; NMR of MAD2 conformational change; crosslinking-MS; MAD2 and HORMAD1 N-terminal truncation mutants in vitro and in vivo

    PMID:28659378 PMID:29208896

    Open questions at the time
    • Full substrate-engaged complex structure not yet available
    • TRIP13 selectivity for free vs. APC/C-bound MCC only partly addressed
  7. 2017 High

    Discovery that biallelic TRIP13 loss-of-function mutations cause severe SAC impairment and chromosome missegregation in human patients established TRIP13 as a disease gene and confirmed its essential SAC role in humans.

    Evidence Exome sequencing of patients; functional rescue of SAC and segregation fidelity in patient-derived cells

    PMID:28553959

    Open questions at the time
    • Full clinical spectrum of TRIP13 deficiency not delineated
    • Relative contribution of meiotic vs. mitotic defects to patient phenotype unclear
  8. 2018 High

    Cryo-EM structures of the TRIP13–p31(comet)–C-MAD2–CDC20 complex revealed the complete substrate-engaged architecture: p31(comet) positions the MAD2 N-terminus into the TRIP13 pore, and sequential ATP-driven translocation unwinds the αA helix to destabilize C-MAD2, providing an atomic-resolution mechanism for HORMA-domain remodeling.

    Evidence Cryo-EM of the quaternary complex; molecular modeling of translocation cycle

    PMID:29973720

    Open questions at the time
    • Real-time dynamics of translocation not observed
    • Whether all six protomers fire sequentially was inferred, not directly shown
  9. 2018 High

    Acute depletion experiments demonstrated that TRIP13 is required both to maintain the O-MAD2 pool needed for checkpoint activation and for catalytic MCC disassembly for checkpoint silencing, resolving the apparent paradox that TRIP13 functions in both SAC activation and inactivation; combining TRIP13 loss with APC15 loss caused permanent mitotic arrest.

    Evidence Degron-mediated acute TRIP13 depletion combined with APC15 knockout; mitotic timing and MCC measurements

    PMID:30341343

    Open questions at the time
    • Quantitative balance between O-MAD2 generation and MCC disassembly rates not modeled
    • Whether TRIP13 is rate-limiting for SAC activation in normal cells unclear
  10. 2020 High

    Extending TRIP13's substrate repertoire beyond MAD2, biochemical and cellular studies showed that TRIP13 converts closed REV7 to open REV7 via p31(comet), disassembling the REV7–Shieldin complex to promote HDR and disassembling REV7–REV3 to suppress translesion synthesis, establishing TRIP13 as a general HORMA-domain remodeler controlling DNA repair pathway choice.

    Evidence REV7 conformational change assays; Co-IP of TRIP13–REV7–Shieldin; HDR/NHEJ reporters; PARP inhibitor resistance in BRCA1-deficient cells

    PMID:31915374 PMID:33051298

    Open questions at the time
    • Structural basis of TRIP13–REV7 engagement not yet determined at this point
    • Relative kinetics of REV7 vs. MAD2 remodeling unknown
  11. 2021 High

    Crystal and cryo-EM structures of the SHLD2–SHLD3–REV7–TRIP13 complex revealed that the C-REV7 N-terminus inserts into the TRIP13 central channel analogously to MAD2, and ATP hydrolysis drives rotatory pulling to disassemble Shieldin, providing the structural basis for TRIP13's role in DNA repair pathway choice.

    Evidence X-ray crystallography of SHLD3–REV7 and SHLD2–SHLD3–REV7; cryo-EM of ATPγS-bound TRIP13–Shieldin complex

    PMID:33597306

    Open questions at the time
    • Dynamics of full Shieldin disassembly cycle not captured
    • Whether additional co-factors regulate TRIP13–Shieldin interaction in vivo unknown
  12. 2021 High

    TRIP13 was shown to enhance USP7-mediated deubiquitination of oncoproteins (NEK2) and tumor suppressors (p53, PTEN), and TRIP13 overexpression accelerated B cell tumorigenesis in transgenic mice, revealing a non-HORMA-domain function in ubiquitin pathway regulation with oncogenic consequences.

    Evidence Co-IP of USP7 with substrates; ubiquitination assays; TRIP13 transgenic mouse tumor model; USP7 inhibitor rescue

    PMID:34061780

    Open questions at the time
    • Whether TRIP13 ATPase activity is required for USP7 enhancement not determined
    • Mechanism by which TRIP13 enhances USP7–substrate association is unclear
    • Whether this function operates through HORMA-domain remodeling or an independent mechanism is unknown
  13. 2024 High

    Direct localization of endogenous TRIP13 to the synaptonemal complex and telomeres throughout meiotic prophase I, independent of axial element proteins, together with dosage-sensitive meiotic defects in heterozygotes, refined understanding of where and when TRIP13 acts during meiosis.

    Evidence FLAG-tagged TRIP13 knockin mice; live imaging and immunofluorescence; Trip13+/− phenotypic analysis

    PMID:39207914

    Open questions at the time
    • Telomeric function of TRIP13 is unexplained mechanistically
    • Identity of TRIP13 recruitment factors at SC and telomeres unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TRIP13's telomeric function, whether TRIP13's enhancement of USP7 deubiquitination requires its ATPase or HORMA-domain remodeling activity, quantitative modeling of how TRIP13 balances O-MAD2 generation with MCC disassembly in living cells, and whether additional non-HORMA substrates exist.
  • Telomeric mechanism unknown
  • USP7 interaction mechanism unresolved
  • No comprehensive substrate profiling beyond HORMA-domain proteins
  • In vivo quantitative flux through TRIP13-dependent pathways not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 8 GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005694 chromosome 3 GO:0005829 cytosol 2
Pathway
R-HSA-1640170 Cell Cycle 7 R-HSA-392499 Metabolism of proteins 6 R-HSA-1474165 Reproduction 5 R-HSA-73894 DNA Repair 5
Partners
CDC20EGFRMAD1L1BP (P31COMET/MAD2L1BP)MAD2L1MAD2L2SHLD2SHLD3USP7
Complex memberships
TRIP13 hexamerTRIP13–p31(comet)–C-MAD2 complexTRIP13–p31(comet)–REV7–Shieldin complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 TRIP13 AAA-ATPase is required for depletion of HORMAD1 and HORMAD2 from synapsed chromosome axes during meiotic prophase; TRIP13 establishes mutually exclusive HORMAD-rich and synapsed (SYCP1-positive) chromatin domains, suggesting TRIP13 remodels HORMA-domain proteins upon synapsis. Genetic loss-of-function in mice (Trip13 mutants) combined with immunofluorescence localization of HORMADs and SC components on meiotic chromosomes PLoS genetics High 19851446
2007 Mouse TRIP13 is required after strand invasion for completing a subset of meiotic recombination events; TRIP13-deficient spermatocytes retain RAD51, BLM, and RPA on chromosomes despite full synapsis. Double-mutant epistasis with Spo11, Mei1, Rec8, and Dmc1 places TRIP13 downstream of or parallel to these recombination/synapsis genes. Trip13-null mouse model; immunostaining of recombination markers; okadaic acid progression assay; genetic epistasis with Spo11, Mei1, Rec8, Dmc1 double mutants PLoS genetics High 17696610
2010 TRIP13 is required for proper synaptonemal complex (SC) formation, efficient synapsis of sex chromosomes, sex body formation, and normal crossover number and distribution; recombination defects appear early after DSB formation, indicating TRIP13 functions in both recombination and higher-order chromosome structure formation. Distinct Trip13 hypomorph and severe alleles in mice; cytological analysis of SC, crossover markers (MLH1, MLH3), and chiasmata PLoS genetics High 20711356
2015 TRIP13 is a protein-remodeling AAA+ ATPase that converts the HORMA-family spindle checkpoint protein MAD2 from the signaling-active 'closed' (C-MAD2) conformer to the inactive 'open' (O-MAD2) conformer. This activity requires the adapter protein p31(comet), which recruits C-MAD2 to TRIP13. The overall hexameric architecture resembles the bacterial unfoldase ClpX, and TRIP13 possesses a substrate-recognition domain related to NSF and p97. Cryo-EM structure of C. elegans PCH-2 (TRIP13 ortholog); in vitro MAD2 conformational conversion assay with purified TRIP13 and p31(comet); biochemical reconstitution eLife High 25918846
2014 TRIP13 binds DNA-PKcs complex proteins that mediate nonhomologous end joining (NHEJ) and promotes NHEJ repair even when homologous recombination is intact; TRIP13 overexpression drives treatment resistance in head and neck cancer, and sensitization to DNA-PKcs inhibitor overcomes this resistance. Mass spectrometry identification of TRIP13-binding partners (DNA-PKcs complex); NHEJ/HR reporter assays; overexpression and knockdown in cancer cells Nature communications Medium 25078033
2014 TRIP13 AAA-ATPase, together with p31(comet), disassembles the Mitotic Checkpoint Complex (MCC) composed of Mad2, BubR1, Bub3, and Cdc20, thereby abrogating inhibition of APC/C and silencing the spindle assembly checkpoint. ATP hydrolysis by TRIP13 is essential for MCC disassembly. TRIP13 localizes to kinetochores and its knockdown delays metaphase-to-anaphase transition. In vitro MCC disassembly assay using HeLa cell extracts; identification of TRIP13 as active factor by fractionation; TRIP13 knockdown in cells with mitotic timing; immunofluorescence showing kinetochore localization The Journal of biological chemistry / Proceedings of the National Academy of Sciences High 25012665 25092294
2015 TRIP13 oligomeric form binds both p31(comet) and MCC; p31(comet) and checkpoint complexes mutually promote each other's binding to TRIP13, suggesting the substrate-binding site of TRIP13 contains subsites specific for p31(comet) and C-Mad2-containing complex, and simultaneous occupancy of both subsites is required for high-affinity binding. Binding assays with purified proteins; TRIP13 pull-down with p31(comet) and MCC components; mutational analysis Proceedings of the National Academy of Sciences of the United States of America Medium 26324890
2017 TRIP13 and p31(comet) catalyze conversion of C-Mad2 to O-Mad2 without disrupting the stably folded core of Mad2, instead causing local unfolding of the Mad2 C-terminal region. Crystal structure of human TRIP13 was determined, and functional residues mediating p31(comet)-Mad2 binding and coupling ATP hydrolysis to local Mad2 unfolding were identified. TRIP13-p31(comet) can only disassemble free MCC, not APC/C-bound MCC. NMR spectroscopy of MAD2 conformational change; crystal structure of human TRIP13; mutagenesis of functional residues; APC/C inhibition assays Nature communications High 29208896
2017 TRIP13 recognizes C-MAD2 with help of adapter protein p31(comet), which binds to the TRIP13 N-terminal domain and positions the disordered MAD2 N-terminus for engagement by TRIP13 'pore loops', which then unfold MAD2 in the presence of ATP. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro and causes SAC defects in cells. Similarly, N-terminal truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, demonstrating a conserved mechanism. X-ray crystallography; crosslinking mass spectrometry; in vitro TRIP13 remodeling assays with truncation mutants; cellular SAC assays; mouse spermatocyte HORMAD1 localization 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 (MAD2NT) to insert into the axial pore of TRIP13 and distorting the ring to initiate remodeling. Sequential ATP-driven translocation of the hexameric ring along MAD2NT pushes upward on and rotates the p31(comet)-C-MAD2 complex, unwinding the αA helix of C-MAD2 required to stabilize the C-MAD2 β-sheet, thus destabilizing C-MAD2 in favor of O-MAD2. Cryo-electron microscopy structures of TRIP13-p31(comet)-C-MAD2-CDC20 complex; molecular modeling Nature High 29973720
2018 TRIP13 catalytic activity is required to maintain a pool of open-state Mad2 (O-Mad2) for MCC assembly (supporting checkpoint activation) and for timely mitotic exit through catalytic MCC disassembly. Combining TRIP13 depletion with elimination of APC15-dependent Cdc20 ubiquitination/degradation results in complete inability to exit mitosis, demonstrating that mitotic exit requires either TRIP13-catalyzed Mad2 removal or APC15-driven Cdc20 degradation. Degron-tagging for rapid TRIP13 depletion; combination with APC15 loss; cell biological mitotic timing assays; MCC assembly/disassembly measurements Nature communications High 30341343
2020 TRIP13 ATPase acts as a negative regulator of REV7 (MAD2L2): TRIP13 catalyzes an inactivating conformational change in REV7 from 'closed' to 'open', dissociating the REV7-Shieldin complex to promote homology-directed repair (HDR). TRIP13 similarly disassembles the REV7-REV3 translesion synthesis (TLS) complex, inhibiting error-prone lesion bypass. TRIP13 overexpression in BRCA1-deficient cancers confers PARP inhibitor resistance by restoring HDR. Biochemical assays of REV7 conformational change; Co-IP showing TRIP13-REV7-Shieldin interaction; HDR/NHEJ reporter assays; PARP inhibitor resistance assays in BRCA1-deficient cells Nature cell biology High 31915374
2020 p31(comet) binds to the REV7-Shieldin complex in cells and promotes REV7 inactivation through the TRIP13 ATPase, causing PARP inhibitor resistance. p31(comet) also counteracts REV7 function in TLS by releasing it from REV3 in the Pol ζ complex. p31(comet) is identified as an important mediator of the TRIP13-REV7 interaction. Co-IP of p31(comet) with REV7-Shieldin complex; REV7 inactivation/chromatin extraction assays; PARP inhibitor resistance assays; TLS bypass assays Proceedings of the National Academy of Sciences of the United States of America High 33051298
2021 MAD2L2 (REV7) dimerization, mediated by SHLD2 and accelerating MAD2L2-SHLD3 interaction, is required for appropriate shieldin function in NHEJ. MAD2L2 dimerization together with SHLD3 allows shieldin to interact with TRIP13 ATPase, and appropriate levels of TRIP13 are important for proper shieldin (dis)assembly and activity in DNA repair. Biochemical characterization of REV7 dimerization; co-IP of shieldin with TRIP13; functional NHEJ assays; dimerization-defective mutants Nature communications High 34521823
2021 Crystal structures of human SHLD3-REV7 binary and SHLD2-SHLD3-REV7 ternary complexes reveal that Shieldin assembly requires SHLD2-SHLD3-induced conformational heterodimerization of open (O-REV7) and closed (C-REV7) forms of REV7. Cryo-EM structures of ATPγS-bound SHLD2-SHLD3-REV7-TRIP13 complexes show that the N-terminus of C-REV7 inserts into the central TRIP13 channel, and ATP hydrolysis-triggered rotatory TRIP13 motions pull the unfolded REV7 N-terminal peptide through the channel to disassemble Shieldin. X-ray crystallography of Shieldin subcomplexes; cryo-EM of TRIP13-Shieldin complex; biochemical disassembly assays Proceedings of the National Academy of Sciences of the United States of America High 33597306
2021 TRIP13 increases cellular deubiquitination by enhancing the association of the deubiquitinase USP7 with its substrates, leading to stabilization of oncoproteins (NEK2) and destabilization of tumor suppressors (PTEN, p53). TRIP13 overexpression accelerates B cell tumor development in transgenic mice. TRIP13 overexpression in mice and cultured cells; ubiquitination assays; Co-IP of USP7 with substrates; transgenic mouse tumor model; USP7 inhibitor rescue The Journal of clinical investigation High 34061780
2017 Biallelic loss-of-function mutations in TRIP13 cause severe spindle assembly checkpoint (SAC) impairment, leading to a high rate of chromosome missegregation in patient cells; restoring TRIP13 function rescues accurate segregation and SAC proficiency. Exome sequencing of patients; functional studies in patient-derived cells; SAC assay; chromosome missegregation quantification; TRIP13 rescue experiment Nature genetics High 28553959
2020 In C. elegans, the TRIP13 ortholog PCH-2 controls spindle checkpoint strength by regulating the availability of inactive O-Mad2 at and near unattached kinetochores. CMT-1 (p31(comet) ortholog) is required for both PCH-2 localization to unattached kinetochores and its enrichment in germline precursor cells, linking PCH-2 checkpoint function to cell volume and cell fate. Genetic manipulation of C. elegans cell volume and CMT-1/PCH-2; Mad2 kinetochore recruitment assays; spindle checkpoint functional assays in different cell types Molecular biology of the cell Medium 32697629
2024 TRIP13 localizes to the synapsed synaptonemal complex (SC) in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. This localization is independent of SC axial element proteins REC8 and SYCP2/SYCP3. TRIP13 functions as a dosage-sensitive regulator of meiosis: heterozygous mice exhibit intermediate meiotic defects between wild-type and null. Live imaging and immunofluorescence in knockin mice with FLAG-tagged TRIP13; Trip13-null and Trip13+/- mouse analysis; co-localization with SC markers eLife High 39207914
2017 TRIP13 is required to disassemble the MCC through p31(comet)-mediated Mad2 conformational change; overexpression of TRIP13 significantly reduces the mitotic delay caused by Mad2 overexpression, while TRIP13 reduction exacerbates it, identifying an unexpected dependency on TRIP13 in Mad2-overexpressing cells that operates specifically on MCC disassembly. TRIP13 overexpression and shRNA knockdown combined with Mad2 overexpression; mitotic timing assays; checkpoint complex disassembly measurements; tumor xenograft proliferation assays Cell reports Medium 28564602
2022 TRIP13 interacts directly with MRE11 (identified by proximity labeling proteomics) and controls the recruitment of MDC1 to DNA damage sites by regulating the MDC1-MRN complex interaction, thereby participating in ATM signaling amplification immediately after DNA strand break sensing. Quantitative proteomics with proximity labeling (BioID); Co-IP of TRIP13-MRE11; MDC1 recruitment assays at DNA damage sites; ATM signaling pathway analysis Cells Medium 36552858
2017 TRIP13 directly interacts with TTC5 (a p53 co-factor); genetic knockdown of TRIP13 in murine tubular cells increases p53 activity at Serine 15, suggesting TRIP13 suppresses p53-dependent apoptosis by sequestering TTC5. Co-IP of TRIP13 with TTC5; siRNA knockdown of TRIP13 in murine IMCD cells; p53 phosphorylation measurement; in vivo IRI kidney model Scientific reports Medium 28256593
2021 TRIP13 directly interacts with ACTN4 and positively regulates its expression, thereby activating the AKT/mTOR pathway to drive hepatocellular carcinoma tumor progression. Co-IP of TRIP13 with ACTN4; Western blot for AKT/mTOR pathway components; gain- and loss-of-function in vitro and xenograft in vivo assays Journal of experimental & clinical cancer research Low 31533816
2019 TRIP13 directly binds to the promoter region of FBXW7 and inhibits its transcription, thereby stabilizing c-MYC (an FBXW7 substrate), promoting GBM cell proliferation and invasion. ChIP showing TRIP13 binding to FBXW7 promoter; TRIP13 knockdown with FBXW7/c-MYC protein measurements; functional proliferation/invasion assays in GBM cells British journal of cancer Medium 31740732
2021 TRIP13 interacts with ACTN4 to activate Wnt/β-catenin signaling in cervical cancer; ACTN4 knockdown reverses TRIP13-mediated Wnt/β-catenin activation, and Wnt/β-catenin inhibition reverses TRIP13-induced cancer-promoting effects. Co-IP of TRIP13 with ACTN4; Wnt/β-catenin pathway reporter; ACTN4 knockdown epistasis; in vivo xenograft Environmental toxicology Low 34061428
2021 TRIP13 interacts with FLNA (filamin A) and activates the PI3K/AKT pathway to promote transcriptional activation of EMT-related genes in melanoma. RNA sequencing; Co-IP and mass spectrometry identification of FLNA as TRIP13 binding partner; PI3K/AKT pathway measurements; in vitro and in vivo invasion assays Journal of oncology Low 36268276
2021 TRIP13 regulates progression of gastric cancer by directly interacting with DDX21 and stabilizing its expression by restraining its ubiquitination degradation; HDAC1 acts as an upstream transcriptional regulator of TRIP13 by binding to the TRIP13 promoter region. Co-IP of TRIP13 with DDX21; ubiquitination assay; ChIP showing HDAC1 at TRIP13 promoter; functional in vitro and in vivo assays Cell death & disease Low 39187490
2021 EGFR phosphorylates TRIP13 at tyrosine 56 in response to radiation, and phospho-TRIP13(Y56) promotes NHEJ repair to confer radiation resistance; suppression of Y56 phosphorylation abrogates these effects. Site-specific mutagenesis of TRIP13 Y56; co-IP with EGFR; NHEJ repair reporter assay; radiation resistance assays in head and neck cancer cells and patient tumors Molecular therapy Medium 34111559
2023 TRIP13 directly interacts with EGFR, modulates its phosphorylation and downstream signaling in bladder cancer cells; co-immunoprecipitation confirms the TRIP13-EGFR interaction. Co-IP of TRIP13 with EGFR; Western blot of EGFR pathway; TRIP13 KD functional assays International journal of biological sciences Low 31337978
2022 TRIP13 forms a trimeric complex with USP7 and c-FLIP in TNBC cells; tetrahydrocurcumin (THC) targets TRIP13 to disrupt the TRIP13/USP7/c-FLIP complex, leading to c-FLIP ubiquitination and extrinsic apoptosis induction. Click chemistry-based target fishing; CETSA; DARTS; SPR; Co-IP of TRIP13-USP7-c-FLIP; in vitro deubiquitination assay; confocal microscopy Journal of advanced research Medium 39505147
2023 TRIP13 interacts with YWHAE and disrupting the TRIP13/YWHAE complex by DCZ5417 inhibits the ERK/MAPK signaling axis; DCZ5417 inhibits TRIP13 ATPase activity directly. Molecular docking; pull-down; surface plasmon resonance; cellular thermal shift; ATPase assay; Co-IP of TRIP13-YWHAE; functional MM cell assays Journal of translational medicine Medium 38012658
2025 TRIP13 promotes survival of KRAS(G12V)-expressing cells specifically through homologous recombination (HR); KRASG12V-expressing cells lacking TRIP13 acquire HR deficiency hallmarks (sensitivity to translesion synthesis inhibitors and PARP inhibitors), establishing TRIP13 as a KRAS-induced HR factor in pancreatic cancer. Genetic (siRNA/CRISPR) and pharmacological TRIP13 depletion in KRASG12V-expressing HPNE cells; HR reporter assays; DNA damage sensitivity assays; xenograft models NAR cancer Medium 40115747
2023 TRIP13 interacts with EGFR and induces its phosphorylation and downstream pathway activation (EGFR signaling) in NSCLC gefitinib-resistant cells; TRIP13 also improves autophagy to desensitize gefitinib in NSCLC cells. Co-IP of TRIP13 with EGFR; immunofluorescence; Western blot of phospho-EGFR; autophagy assays; TRIP13 overexpression/knockdown in resistant cells Oncology reports Low 36896765

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 327 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 159 20711356
2015 TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching. eLife 142 25918846
2014 TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer. Nature communications 130 25078033
2020 TRIP13 regulates DNA repair pathway choice through REV7 conformational change. Nature cell biology 126 31915374
2020 HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity. Molecular cell 125 31932165
2014 Thyroid hormone receptor interacting protein 13 (TRIP13) AAA-ATPase is a novel mitotic checkpoint-silencing protein. The Journal of biological chemistry 123 25012665
2017 Biallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation. Nature genetics 118 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 99 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 TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis. British journal of cancer 61 31740732
2019 Insights into a Crucial Role of TRIP13 in Human Cancer. Computational and structural biotechnology journal 60 31321001
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 48 33648560
2018 Silencing TRIP13 inhibits cell growth and metastasis of hepatocellular carcinoma by activating of TGF-β1/smad3. Cancer cell international 46 30564064
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 42 35194944
2020 TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status. Molecular oncology 42 33037736
2017 Mad2 Overexpression Uncovers a Critical Role for TRIP13 in Mitotic Exit. Cell reports 42 28564602
2017 Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing. Nature communications 36 29208896
2021 TRIP13 modulates protein deubiquitination and accelerates tumor development and progression of B cell malignancies. The Journal of clinical investigation 35 34061780
2016 TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion. Oncology letters 35 28105232
2021 MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair. Nature communications 33 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
2019 Elevated TRIP13 drives cell proliferation and drug resistance in bladder cancer. American journal of translational research 28 31396344
2022 Trip13 Depletion in Liver Cancer Induces a Lipogenic Response Contributing to Plin2-Dependent Mitotic Cell Death. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 26 36031387
2019 Increased expression of TRIP13 drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway. International journal of biological sciences 26 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
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
2022 Evaluation of the TRIP13 level in breast cancer and insights into potential molecular pathways. Journal of cellular and molecular medicine 21 35322916
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
2023 Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells. Cell death discovery 19 37669963
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
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 18 34111559
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
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
2024 TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis. eLife 14 39207914
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
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 14 31648166
2023 Targeting of oncogenic AAA-ATPase TRIP13 reduces progression of pancreatic ductal adenocarcinoma. Neoplasia (New York, N.Y.) 12 38039923
2023 The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13-MAPK-YWHAE signaling pathway. Journal of translational medicine 11 38012658
2022 TRIP13 knockdown inhibits the proliferation, migration, invasion, and promotes apoptosis by suppressing PI3K/AKT signaling pathway in U2OS cells. Molecular biology reports 10 35032258
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 Clinical Significance and Systematic Expression Analysis of the Thyroid Receptor Interacting Protein 13 (TRIP13) as Human Gliomas Biomarker. Cancers 10 34066132
2021 DNA damage is overcome by TRIP13 overexpression during cisplatin nephrotoxicity. JCI insight 10 34806647
2019 The oncogenic role of TRIP13 in regulating proliferation, invasion, and cell cycle checkpoint in NSCLC cells. International journal of clinical and experimental pathology 10 31934178
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
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 Inducing Synergistic DNA Damage by TRIP13 and PARP1 Inhibitors Provides a Potential Treatment for Hepatocellular Carcinoma. Journal of Cancer 8 35517402
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
2020 The conserved AAA-ATPase PCH-2 TRIP13 regulates spindle checkpoint strength. Molecular biology of the cell 8 32697629
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 7 39505147
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 TRIP13 Activates Glycolysis to Promote Cell Stemness and Strengthen Doxorubicin Resistance of Colorectal Cancer Cells. Current medicinal chemistry 6 38347785
2024 Targeting TRIP13 in favorable histology Wilms tumor with nuclear export inhibitors synergizes with doxorubicin. Communications biology 6 38589567
2024 TRIP13 regulates progression of gastric cancer through stabilising the expression of DDX21. Cell death & disease 6 39187490
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
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
2025 Exosome-transmitted HSPA9 facilitates bortezomib resistance by targeting TRIP13/USP1 signaling in multiple myeloma. Cell communication and signaling : CCS 4 40140922
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
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
2024 Role of TRIP13 in human cancer development. Molecular biology reports 3 39436503
2023 TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis. bioRxiv : the preprint server for biology 3 37808842
2023 An integrated computational biology approach defines the crucial role of TRIP13 in pancreatic cancer. Computational and structural biotechnology journal 3 38074464
2025 TRIP13-induced NUSAP1 upregulation promotes CcRCC progression through EMT and PI3K/AKT/mTOR pathway. Journal of translational medicine 2 40790482
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
2025 Repeated ionizing radiation exposure induces TRIP13 expression, conferring radioresistance in lung cancer cells. Scientific reports 1 39762328
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
2025 A homozygous TRIP13 pathogenic variant associated with familiar oocyte arrest and prematurely condensed sperm chromosomes. Molecular cytogenetics 1 40702521
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 Genome-wide methylation profiling of Peripheral T-cell lymphomas identifies TRIP13 as a critical driver of tumor proliferation and survival. Research square 1 38464090
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