Affinage

TPX2

Targeting protein for Xklp2 · UniProt Q9ULW0

Length
747 aa
Mass
85.7 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPX2 is a Ran-regulated, microtubule-associated spindle assembly factor that couples Aurora A kinase activation to spatially controlled microtubule nucleation during mitosis (PMID:10871281, PMID:12177045, PMID:26414402). Through its N-terminus it directly binds the Aurora A catalytic domain and allosterically activates the kinase by pulling on the activation segment to bury the phosphothreonine in the active conformation and shield it from phosphatase action, an activation that operates even on dephosphorylated Aurora A and increases catalytic efficiency by raising affinity for ATP and substrate (PMID:14580337, PMID:24867643, PMID:17705509); the same interaction targets Aurora A to spindle microtubules and protects it from APC/C-Cdh1–dependent proteasomal degradation independently of kinase activation (PMID:12177045, PMID:21147853). TPX2 promotes microtubule assembly by directly stabilizing nucleation intermediates and growing plus ends, suppressing tubulin off-rates, and co-condensing with tubulin via phase separation on pre-existing microtubules, and it activates γ-TuRC-dependent branching nucleation through dedicated nucleation-activator motifs that bind tubulin across longitudinal and lateral interfaces using flexibly linked 'ridge' and 'wedge' elements (PMID:26414402, PMID:26869224, PMID:31937751, PMID:28264915, PMID:29120325). Its C-terminal domain regulates the mitotic kinesins Eg5 and Kif15, controlling spindle pole segregation, spindle size, and motor motility (PMID:18372177, PMID:26018074, PMID:27852894, PMID:25070954). These activities are spatially gated by importin-α/β, which binds TPX2 with nanomolar affinity over a region overlapping its microtubule- and nucleation-interaction surfaces and inhibits its phase separation until released by RanGTP or by competing factors such as GM130 near membranes and chromatin (PMID:34302807, PMID:29120325, PMID:31937751, PMID:33526712). TPX2 is essential for spindle bipolarity and faithful chromosome segregation in vivo, and its haploinsufficiency drives aneuploidy and tumorigenesis (PMID:22266221, PMID:10871281). Beyond mitosis, nuclear TPX2 amplifies the DNA double-strand break response through ATM/MDC1 and an Aurora A–53BP1 axis governing end resection and fork protection, and maintains H4K16 acetylation via SIRT1 (PMID:23045526, PMID:30602538, PMID:25365214). TPX2 activity is further tuned by CDK1/2 phosphorylation at Thr72 governing spindle localization, CDK5 phosphorylation at Ser486 promoting stability, and K249 lactylation that disrupts PP1 binding to Aurora A to enhance kinase activity (PMID:25688093, PMID:31272499, PMID:40107714).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Established TPX2 as a microtubule-associated protein essential for spindle pole organization, answering whether a dedicated factor links chromatin-proximal microtubule density to bipolar spindle architecture.

    Evidence Xenopus egg extract immunodepletion/add-back with immunofluorescence and motor-targeting assays

    PMID:10871281

    Open questions at the time
    • Molecular activity driving nucleation undefined
    • No mechanism linking TPX2 to a kinase partner yet
    • Ran/importin regulation not addressed
  2. 2002 High

    Identified Aurora A as a direct TPX2 partner and showed TPX2 targets Aurora A to spindle microtubules, defining the physical link between a spindle MAP and a mitotic kinase.

    Evidence Reciprocal Co-IP with MS, siRNA knockdown, immunofluorescence, and in vitro binding/kinase assays in human cells

    PMID:12177045

    Open questions at the time
    • Structural basis of activation not resolved
    • Functional consequence of TPX2 phosphorylation unknown
  3. 2003 High

    Resolved the structural mechanism of Aurora A activation, showing TPX2 swings the phosphothreonine into a buried active position and shields it from dephosphorylation without global conformational change.

    Evidence X-ray crystallography of Aurora A ± TPX2 fragment with kinase activity assays; supported by in vitro mutagenesis defining the Aurora A–binding motif

    PMID:14580337 PMID:14701852

    Open questions at the time
    • Whether activation occurs on unphosphorylated kinase unresolved
    • Cellular regulation of the interaction not addressed
  4. 2004 High

    Dissected TPX2 into separable functional modules, showing the N-terminus binds/nucleates microtubules and the C-terminus mediates RanGTP-dependent spindle assembly in a factor network.

    Evidence Domain truncation/add-back in Xenopus egg extract with in vitro MT polymerization assays

    PMID:15385625

    Open questions at the time
    • Identity of C-terminal network partners undefined
    • Mechanism of nucleation by N-terminus not molecularly resolved
  5. 2006 Medium

    Placed TPX2/Aurora A within a Plk1-headed hierarchical cascade and revealed a postmitotic nuclear-assembly role via LAP2, broadening TPX2 function beyond spindle MTs.

    Evidence RNAi epistasis in mammalian cells; Xenopus nuclear assembly extract depletion with LAP2 pulldown

    PMID:16418575 PMID:16735579

    Open questions at the time
    • Direct vs indirect Plk1–TPX2 link unclear
    • TPX2–LAP2 interaction mechanism limited to single study
  6. 2008 Medium

    Defined the C-terminal Eg5-interacting domain as driving spindle pole segregation and showed TPX2 controls meiotic spindle pole integrity via Aurora A–TACC3, distinguishing motor-regulatory from kinase-activation roles.

    Evidence Xenopus embryo microinjection with Eg5 rescue; mouse oocyte RNAi with live imaging

    PMID:18372177 PMID:18833336

    Open questions at the time
    • Biophysical mode of Eg5 regulation not resolved
    • Single-lab in vivo systems
  7. 2010 High

    Showed TPX2 stabilizes Aurora A against APC/C-Cdh1 proteasomal degradation, establishing a kinase-activity-independent function of the Aurora A–binding region.

    Evidence siRNA, proteasome inhibition, and domain-specific rescue with Co-IP in human cells

    PMID:21147853

    Open questions at the time
    • Direct competition with degradation machinery not structurally defined
  8. 2012 High

    Demonstrated in vivo essentiality and tumor-suppressive dosage sensitivity, and uncovered a nuclear DNA-damage-response role, expanding TPX2 beyond mitosis.

    Evidence Conditional Tpx2 knockout mouse genetics with tumor analysis; siRNA + ionizing radiation with γ-H2AX readouts, Co-IP for MDC1/ATM, and pharmacological epistasis

    PMID:22266221 PMID:23045526

    Open questions at the time
    • Mechanism of TPX2 recruitment to DSBs undefined
    • Whether DDR role requires Aurora A unresolved at this stage
  9. 2014 High

    Resolved that TPX2 allosterically activates even dephosphorylated Aurora A and linked nuclear TPX2 to H4K16ac maintenance via SIRT1 and to CPC scaffolding, refining both the activation model and TPX2's chromatin roles.

    Evidence X-ray crystallography/NMR of dephospho Aurora A–TPX2 dimer; Co-IP and siRNA for SIRT1/H4K16ac; Xenopus extract depletion and in vitro Aurora B kinase assays

    PMID:22560880 PMID:24867643 PMID:25365214

    Open questions at the time
    • SIRT1 and CPC links rest on single Medium-confidence studies
    • Physiological balance between Aurora A and Aurora B activation unclear
  10. 2015 High

    Reconstituted TPX2's intrinsic microtubule nucleation and Eg5-inhibitory activities with purified proteins, and identified CDK1/2 phosphorylation at Thr72 as a spindle-localization switch, converting cellular phenotypes into defined biochemical mechanisms.

    Evidence In vitro TIRF reconstitution with chTOG and importins; single-molecule Eg5 assays; in vitro CDK kinase assays with phospho-mutant cell biology; neuronal kinesin-5 domain rescue

    PMID:25688093 PMID:26018074 PMID:26257190 PMID:26414402

    Open questions at the time
    • Relationship between MT stabilization and γ-TuRC activation not yet integrated
    • In vivo significance of Thr72 phosphorylation limited to one study
  11. 2016 High

    Mechanistically explained TPX2's effect on MT dynamics as suppression of tubulin off-rates, mapped Kif15 regulation to the C-terminus, and defined an allosteric Aurora A–TPX2 inhibition pocket, advancing both dynamics and druggability.

    Evidence Quantitative in vitro TIRF assays with simulations; domain-deletion kinesin assays in cells and in vitro; X-ray crystallography of the AurkinA Y-pocket inhibitor; overexpression phenotypes in RPE-1 cells

    PMID:26869224 PMID:27339427 PMID:27852894 PMID:32041138

    Open questions at the time
    • Quantitative dynamics model from single lab
    • Excess-TPX2 nuclear phenotype mechanism Aurora A-independent but otherwise unresolved
  12. 2017 High

    Defined the structural basis of TPX2–microtubule binding and the γ-TuRC nucleation-activator motifs, separating general MT binding from branching-nucleation activation and explaining importin competition.

    Evidence Cryo-EM of TPX2 on the MT surface with in vitro reconstitution; separation-of-function mutagenesis with γ-TuRC binding and branching assays in Xenopus extract

    PMID:28264915 PMID:29120325

    Open questions at the time
    • Structure of the TPX2–γ-TuRC complex not resolved
    • How phosphorylation modulates these interfaces unclear
  13. 2019 Medium

    Established a TPX2/Aurora A–53BP1 axis controlling homologous recombination and stalled-fork protection, and identified CDK5-Ser486 phosphorylation as a stability/tumorigenicity driver, deepening interphase and oncogenic functions.

    Evidence Co-IP, siRNA epistasis with DNA fiber and HR reporter assays; phosphoproteomics with CDK5 kinase assays and xenografts

    PMID:30602538 PMID:31272499

    Open questions at the time
    • Single-lab Co-IP/epistasis for the 53BP1 axis
    • Direct vs indirect CDK5 effect on TPX2 stability not fully resolved
  14. 2020 High

    Demonstrated that TPX2 drives microtubule nucleation by phase-separating into a tubulin co-condensate on pre-existing microtubules, with importin-α/β inhibiting condensation, providing a biophysical basis for branching nucleation and its spatial control.

    Evidence In vitro phase separation and cytosol-based nucleation assays with importin competition and truncation analysis

    PMID:31937751

    Open questions at the time
    • Whether condensation is required in vivo not directly tested
    • Link between condensate and γ-TuRC activation not mechanistically joined
  15. 2021 Medium

    Quantified the importin-α/β trimer interaction (including a new NLS), mapped a WDR62-katanin severing axis and a GM130/CDK1-importin-α competition mechanism for local astral-MT activation, integrating spatial regulation of TPX2.

    Evidence ITC/pull-down and NLS mapping with phase-separation assays; in vitro katanin severing reconstitution with Co-IP; phospho-mutant importin-α rescue and spindle-orientation assays

    PMID:33526712 PMID:34137789 PMID:34302807

    Open questions at the time
    • WDR62 and GM130 axes each rest on single Medium-confidence studies
    • Interplay between multiple spatial cues in cells not unified
  16. 2023 Medium

    Linked TPX2 to nuclear Aurora A accumulation driving protumorigenic processes, identified NDC80 as a checkpoint-coupled Aurora A–TPX2 substrate regulated by PP6, and showed TPX2 enhances PXR-driven drug resistance, connecting TPX2 activity to substrate phosphorylation and cancer phenotypes.

    Evidence Co-overexpression with proteasome inhibition and mammosphere assays; PPP6C knockout with NDC80-9A phospho-mutant rescue and phosphoproteomics; Co-IP/ChIP/reporter assays for PXR

    PMID:36707511 PMID:36797043 PMID:36897279

    Open questions at the time
    • Single-lab studies for each mechanism
    • Direct vs indirect TPX2 contribution to nuclear Aurora A localization not fully separated
  17. 2025 Medium

    Identified K249 lactylation as a metabolite-driven PTM that disrupts PP1 binding to Aurora A and enhances Aurora A T288 phosphorylation, connecting metabolic state to TPX2/Aurora A activity and tumor growth.

    Evidence MS site identification, CBP/HDAC1 writer/eraser knockdown, PP1 Co-IP, Aurora A pT288 western blot, and xenograft models

    PMID:40107714

    Open questions at the time
    • Single-lab study
    • Structural basis of lactylation-induced PP1 displacement unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TPX2's distinct activities — Aurora A activation, γ-TuRC branching nucleation, phase separation, kinesin regulation, and nuclear DDR/chromatin roles — are coordinated in space and time across the cell cycle, and how its many PTMs are integrated, remains unresolved.
  • No integrated structural/functional model of the TPX2–γ-TuRC–tubulin condensate in cells
  • Cross-talk between mitotic and interphase TPX2 functions undefined
  • Combinatorial logic of Thr72/Ser486 phosphorylation and K249 lactylation untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005856 cytoskeleton 3 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-73894 DNA Repair 2
Partners
AURKAKIF11KIF15KPNA2KPNB1SIRT1TP53BP1WDR62
Complex memberships
Aurora A–TPX2 complexChromosomal Passenger Complex (Aurora B)TPX2–importin-α/β trimer

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Crystal structures of phosphorylated Aurora-A with and without a 43-residue TPX2 domain revealed the molecular mechanism of Aurora-A activation: TPX2 binding pulls on the Aurora-A activation segment, swinging the phosphothreonine (pThr) into a buried position and locking the active conformation, while also protecting pThr from phosphatase-mediated dephosphorylation. No global conformational changes in the kinase are induced. X-ray crystallography (crystal structures of Aurora-A ± TPX2 fragment), biochemical kinase activity assays Molecular cell High 14580337
2002 Human TPX2 directly binds the C-terminal catalytic domain of Aurora-A via its N-terminus (reciprocal co-IP from mitotic HeLa extracts and direct binding studies). TPX2 is required for targeting Aurora-A to spindle microtubules (not spindle poles); depletion of TPX2 by siRNA abolishes Aurora-A association with microtubules. Conversely, Aurora-A depletion has no effect on TPX2 localization. Aurora-A phosphorylates TPX2. Reciprocal co-immunoprecipitation, mass spectrometry identification, siRNA knockdown, immunofluorescence localization, in vitro binding and kinase assays The Journal of cell biology High 12177045
2000 Xenopus TPX2 is a microtubule-associated protein required for spindle pole organization. It is nuclear during interphase and localizes to spindle poles in mitosis in a dynein-dynactin-dependent manner. Immunodepletion from mitotic egg extracts causes bipolar structures with disintegrating poles and decreased microtubule density; excess TPX2 causes monopolar structures with enlarged poles. TPX2 also targets Xklp2 to microtubule minus ends. Xenopus egg extract immunodepletion/add-back, immunofluorescence, biochemical fractionation The Journal of cell biology High 10871281
2003 In Xenopus, Aurora A autophosphorylation requires only Thr-295 for activity. TPX2 binding activates Aurora A and leads to phosphorylation of three Ser residues in the N-terminus of TPX2; mutation of these sites does not affect Aurora A activation. Mutation of a putative Aurora A-binding motif in TPX2 abolishes both TPX2 phosphorylation and Aurora A activation. p53 blocks Aurora A activity, and TPX2 inhibits this p53-mediated inhibition. In vitro kinase assays, site-directed mutagenesis, biochemical binding assays with Xenopus proteins The Journal of biological chemistry High 14701852
2004 Domain analysis of Xenopus TPX2 shows: the large N-terminal domain (containing the Aurora A binding peptide) directly binds microtubules and nucleates MTs in pure tubulin but cannot rescue spindle assembly in TPX2-depleted extract. The large C-terminal domain (lacking Aurora A binding) does not bind pure MTs directly but rescues RanGTP-dependent microtubule nucleation and spindle assembly in depleted extract, indicating the C-terminus functions in a network with other RanGTP-regulated factors. Xenopus egg extract immunodepletion, domain truncation/add-back experiments, in vitro MT polymerization assays Molecular biology of the cell High 15385625
2006 Aurora-A and Plk1 are part of a hierarchical signaling cascade in spindle formation: Plk1 controls the localization of Aurora-A to centrosomes and TPX2 recruitment to microtubules. Aurora-A and TPX2 are required for centriole cohesion and spindle bipolarity; TPX2 also contributes to centrosome maturation independently of its microtubule organization role. RNA interference knockdown of Aurora-A, Plk1, and TPX2 individually and in combination, immunofluorescence, epistasis analysis in mammalian cells Cell cycle (Georgetown, Tex.) Medium 16418575
2008 The C-terminal domain of Xenopus TPX2 contains a discrete Eg5-interacting domain. Injection of TPX2-C-terminus into embryos causes spindle collapse and failure of pole segregation; these phenotypes require the Eg5-binding region and are rescued by Eg5 injection. This defines a novel Eg5-dependent role of TPX2 C-terminus in spindle pole segregation. Xenopus embryo microinjection, Xenopus S3 cell transfection, in vitro binding assays, live imaging Current biology : CB Medium 18372177
2008 In mouse oocytes, TPX2 protein accumulates from meiosis I to II and controls spindle assembly via two distinct functions: (1) microtubule assembly regulation and (2) spindle pole integrity via Aurora A-dependent phosphorylation of TACC3, a regulator of MTOC activity. RNAi depletion of TPX2 and live imaging demonstrated these requirements. RNAi depletion, live cell imaging, immunofluorescence, mouse oocyte meiotic system PloS one Medium 18833336
2010 TPX2 protects Aurora-A from proteasomal degradation in both interphase and mitosis in human cells. Aurora-A levels decrease in TPX2-silenced G2 and prometaphase cells in a proteasome- and Cdh1/APC-C-dependent manner. Reintroduction of full-length TPX2 or its Aurora-A-binding region restores Aurora-A levels; a truncated TPX2 lacking this domain cannot. This stability function is independent of TPX2's ability to activate Aurora-A or localize it to the spindle. siRNA silencing, proteasome inhibitor treatment, rescue with truncation constructs, co-immunoprecipitation, immunofluorescence, western blotting in human cells Journal of cell science High 21147853
2011 TPX2 acts as a scaffold and co-activator of the Chromosomal Passenger Complex (CPC): immunodepletion of TPX2 from Xenopus egg extracts decreases Aurora B-Survivin and Aurora B-INCENP interactions, reducing Aurora B activity. TPX2 residues 138–328 are sufficient to enhance Aurora B-Survivin association and Aurora B kinase activity in vitro. Overexpression of this region in HeLa cells causes metaphase chromosome alignment defects and INCENP mislocalization. Xenopus egg extract immunodepletion, in vitro Aurora B kinase assays, HeLa cell transfection, immunofluorescence Cellular signalling Medium 22560880
2012 TPX2 is required for spindle function and chromosome segregation in the mouse embryo. Conditional Tpx2 knockout in primary mouse cultures causes deficient microtubule nucleation from DNA and aberrant spindles during prometaphase, with cells exiting mitosis without chromosome segregation. Tpx2 haploinsufficiency leads to aneuploidy accumulation in vivo and increased susceptibility to spontaneous lymphomas and lung tumors. Conditional null mouse genetics, primary cell culture, immunofluorescence, flow cytometry, in vivo tumor analysis Cancer research High 22266221
2012 Nuclear TPX2 plays a role in the DNA double-strand break response: loss of TPX2 leads to aberrantly high and transient accumulation of γ-H2AX (Ser139-phosphorylated H2AX) at G0/G1 after ionizing radiation, with more numerous high-intensity γ-H2AX foci. Overexpression reduces γ-H2AX after IR. TPX2 accumulates at DSBs and associates (by co-IP) with MDC1 and ATM. Pharmacological inhibition or depletion of ATM or MDC1 (but not DNA-PK) antagonizes the γ-H2AX phenotype caused by TPX2 depletion. siRNA depletion, ionizing radiation, γ-H2AX immunofluorescence and flow cytometry, co-immunoprecipitation, pharmacological inhibitors, cell fractionation The Journal of biological chemistry Medium 23045526
2014 Elucidate molecular mechanism of Aurora A autophosphorylation as intermolecular in a long-lived dimer (resolved by X-ray crystallography and functional assays). TPX2 allosterically activates dephosphorylated Aurora A by binding a conserved hydrophobic groove, shifting the equilibrium toward the active conformation—distinct from phosphorylation-mediated activation. Crystal structure of dephosphorylated Aurora A-TPX2(1-25) domain-swapped dimer reported. X-ray crystallography, NMR, functional kinase assays, site-directed mutagenesis eLife High 24867643
2014 Nuclear TPX2 constitutively controls the levels of histone H4 acetylated at Lys16 (H4K16ac) during G1 phase: TPX2 depletion decreases H4K16ac, and this decrease correlates with increased γ-H2AX after IR. TPX2 interacts (by co-IP) with SIRT1, which is identified as a novel TPX2 complex partner. TPX2 depletion also impairs 53BP1 ionizing radiation-induced foci formation. siRNA depletion, immunofluorescence, flow cytometry, co-immunoprecipitation, western blot for H4K16ac PloS one Medium 25365214
2014 TPX2 levels modulate meiotic spindle size and architecture in Xenopus through Eg5: elevated TPX2 in X. tropicalis extracts reduces spindle length and recruits Eg5 to poles, increasing MT density there. Higher TPX2 partitions MTs between an antiparallel array (spindle expansion) and a parallel cross-linked architecture at spindle poles via Eg5. Xenopus egg extract manipulation, TPX2 immunodepletion and add-back, Eg5 inhibition, immunofluorescence quantification The Journal of cell biology Medium 25070954
2015 Human TPX2 directly stabilizes growing microtubule ends and stimulates microtubule nucleation by stabilizing early nucleation intermediates (using in vitro reconstitution with purified proteins). chTOG alone only weakly promotes nucleation but acts synergistically with TPX2. Importins block TPX2 interaction with nucleation intermediates selectively, controlling nucleation efficiency. In vitro dynamic reconstitution assays with purified human proteins, TIRF microscopy, importin competition assays Nature cell biology High 26414402
2015 TPX2 inhibits the mitotic kinesin Eg5 through two mechanisms: (1) direct binding to microtubules (apparent Kd ~200 nM, independent of tubulin C-terminal tails) and (2) interaction with the Eg5 motor/neck region requiring Eg5 dimerization. Full-length TPX2 dramatically reduces Eg5 velocity in single-molecule TIRF assays; a C-terminal truncation lacking the Eg5-binding domain is a less effective inhibitor. TIRF single-molecule assays, microtubule gliding assays, co-sedimentation, fluorescence microscopy with mammalian cell extracts The Journal of biological chemistry High 26018074
2015 TPX2 regulates neuronal morphology through its kinesin-5 (Eg5) interacting domain: TPX2 depletion from cultured neurons speeds axon outgrowth similarly to kinesin-5 inhibition; re-expression of TPX2 rescues the phenotype, but not if the kinesin-5-interacting domain is deleted. siRNA depletion, domain-deletion rescue in primary cultured neurons, morphological quantification Cytoskeleton (Hoboken, N.J.) Medium 26257190
2016 TPX2 suppresses tubulin subunit off-rates from microtubule ends during both assembly and disassembly, enabling unprecedentedly slow plus-end growth rates and dramatically reduced shortening rates. Computational simulations explain these dynamics by a moderate increase in tubulin-tubulin bond strength upon TPX2 lattice association. In vitro TIRF microscopy-based dynamic MT assembly assays, computational simulations Journal of cell science Medium 26869224
2016 AurkinA, a small-molecule inhibitor of the Aurora A-TPX2 PPI, binds to a hydrophobic 'Y-pocket' on Aurora A that normally accommodates a conserved Tyr-Ser-Tyr motif from TPX2, inducing structural changes that inhibit catalytic activity without affecting ATP binding. This defines an allosteric inhibition mechanism and confirms the Y-pocket as a key regulatory site. Cells exposed to AurkinA mislocalize Aurora A from spindle microtubules. X-ray crystallography, in vitro kinase assays, cell-based immunofluorescence Scientific reports High 27339427
2016 The C-terminal domain of TPX2 contributes to localization and motility of both Eg5 and Kif15 (kinesin-12) to spindle microtubules in cells, and suppresses Kif15 motor walking in vitro. Kif15-dependent bipolar spindle formation in the absence of Eg5 activity requires the C-terminal domain of TPX2. Kif15 puncta move toward the spindle equator at a rate equivalent to microtubule growth; paclitaxel treatment suppresses this movement. TPX2 domain deletion/rescue in cells, in vitro single-molecule kinesin assays, live cell imaging, paclitaxel treatment Molecular biology of the cell Medium 27852894
2017 Cryo-EM structure of a central region of TPX2 bound to the microtubule surface shows TPX2 uses two flexibly linked elements ('ridge' and 'wedge') to simultaneously bind across longitudinal and lateral tubulin interfaces. These MT-interacting elements overlap with the importin-binding site on TPX2. Fluorescence microscopy-based in vitro reconstitution assays confirm this interaction mode is critical for MT binding and nucleation. Cryo-electron microscopy, in vitro MT reconstitution/TIRF microscopy, importin competition assays eLife High 29120325
2017 Structural analysis of Xenopus TPX2 defines its minimal domain for branching MT nucleation, which requires newly identified γ-TuRC nucleation activator motifs (distinct from general MT-binding/bundling ability). Separation-of-function mutations leave TPX2 binding to γ-TuRC intact but abolish branching MT nucleation, indicating TPX2 activates γ-TuRC to promote branching nucleation. Domain truncation/mutation analysis, γ-TuRC binding assays, Xenopus egg extract branching MT nucleation assays, immunofluorescence The Journal of cell biology High 28264915
2019 CDK5 phosphorylates TPX2 at serine 486, promoting TPX2 protein stability (phosphorylation-dependent stabilization). This CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular proliferation and tumorigenicity; TPX2 silencing restores normal migration in CDK5-overexpressing HCC cells. Comparative phosphoproteomics screening, in vitro and in vivo CDK5 kinase assays, site-directed mutagenesis (S486), western blot, xenograft models Journal of experimental & clinical cancer research : CR Medium 31272499
2019 TPX2/Aurora A heterodimer (nominally a mitotic complex) acts as a novel binding partner of 53BP1 in a DNA damage context. Loss of TPX2 or Aurora A compromises DNA end resection, BRCA1 and Rad51 recruitment, and homologous recombination. Loss of TPX2 or Aurora A also causes deprotection of stalled replication forks by failing to counteract MRE11 nuclease activity. Concurrent 53BP1 loss rescues BRCA1/Rad51 recruitment and fork instability upon TPX2 loss. Co-immunoprecipitation, siRNA knockdown, DNA fiber assays, HR reporter assays, epistasis by double knockdown The Journal of cell biology Medium 30602538
2020 TPX2 phase separates into a co-condensate with tubulin, which mediates microtubule nucleation in vitro and in isolated cytosol. Co-condensation preferentially occurs on pre-existing microtubules (site of branching nucleation) at endogenous TPX2 concentrations. Importin-α/β heterodimer inhibits TPX2 condensation in vitro, thereby inhibiting branching MT nucleation activity in cytosol. In vitro phase separation assays, droplet formation microscopy, cytosol-based MT nucleation assays, importin competition, TPX2 truncation/chimera analysis Nature communications High 31937751
2020 Excess TPX2 causes aberrantly stable microtubules at mitotic exit that interfere with nuclear reconstitution and lamin B1 network assembly, resulting in doughnut-shaped daughter nuclei. This phenotype is independent of TPX2's interaction with Aurora-A (shown using a truncated TPX2 unable to bind Aurora-A). TPX2 overexpression (full-length and Aurora-A-binding truncation) in non-transformed hTERT RPE-1 cells, immunofluorescence, live imaging Cells Medium 32041138
2021 TPX2 interacts with importin-α/β in a 1:1:1 monodispersed trimer with nanomolar affinity. A new nuclear localization sequence in TPX2 contributes to high-affinity importin-α binding; TPX2 also interacts with importin-β via dispersed weak interactions. Both importin-α and importin-β interactions inhibit TPX2 phase separation, which enhances branching MT nucleation. Biochemical binding assays (ITC, pull-down), NLS mapping, phase separation assays with importin competition, size exclusion chromatography The Journal of biological chemistry High 34302807
2021 WDR62 functions as an adaptor protein between TPX2/Aurora A and katanin at the spindle pole: TPX2/Aurora A recruits WDR62 to the spindle pole; WDR62 complexed with TPX2/Aurora A (but not WDR62 alone) potently promotes katanin-mediated severing of GDP-MTs in vitro. A TPX2-Aurora A-WDR62-katanin signaling axis in cells regulates spindle dynamics. Co-IP, in vitro MT severing reconstitution, domain binding assays, spindle pole fractionation, live cell imaging The Journal of cell biology Medium 34137789
2021 TPX2 regulates astral microtubule assembly and spindle orientation: GM130 on Golgi membranes activates TPX2 locally by competing with importin-α1 (KPNA2) for TPX2 binding. CDK1 phosphorylates importin-α at serine 62 during mitosis, switching its substrate preference from TPX2 to GM130 and thereby enabling competition-based TPX2 activation. Importin-α S62A mutation impedes local TPX2 activation, compromises astral MT formation, and results in misoriented spindles. Co-immunoprecipitation, phospho-specific mutants of importin-α, RNAi, immunofluorescence, spindle orientation assays Journal of cell science Medium 33526712
2023 Aurora A nuclear localization is promoted by co-overexpression with TPX2 and counteracted by proteasomal degradation. TPX2 co-overexpression (but not Aurora A overexpression alone) is required for Aurora A nuclear accumulation in interphase. In MCF10A mammospheres, TPX2 co-overexpression drives protumorigenic processes downstream of nuclear Aurora A. AURKA, TPX2, and the import regulator CSE1L are co-overexpressed in tumors. Co-overexpression experiments, proteasome inhibitor treatment, immunofluorescence quantification of nuclear localization, mammosphere assays Life science alliance Medium 36797043
2023 PP6 (phosphatase, PPP6C catalytic subunit) regulates Aurora A-TPX2 complex activity at kinetochores: loss of PP6 amplifies Aurora A activity and enlarges spindles with defective chromosome separation. Aurora A-TPX2 phosphorylates NDC80 on multiple N-terminal sites exclusively at checkpoint-silenced, MT-attached kinetochores; NDC80 phospho-deficient 9A mutant reduces spindle size and suppresses nuclear structure defects in PPP6C KO cells. NDC80 phosphorylation is Aurora B-independent. Phosphoproteomics, genetic knockout (PPP6C), phospho-specific antibodies, NDC80-9A mutant rescue, immunofluorescence The Journal of cell biology Medium 36897279
2015 Phosphorylation of TPX2 at Thr72 by CDK1/2 (in vitro and in vivo, cell cycle-dependent, peaking at M phase) regulates TPX2 spindle localization: endogenous TPX2-pThr72 does not associate with spindle; GFP-TPX2 T72A (non-phosphorylatable) preferentially concentrates on the spindle compared to wild-type. T72A overexpression increases multipolar spindles and is associated with elevated Aurora A and Eg5 activity. In vitro CDK1/2 kinase assays, phospho-specific antibody generation, cell cycle synchronization, GFP-TPX2 mutant transfection, immunofluorescence The Journal of biological chemistry Medium 25688093
2006 TPX2 is required for postmitotic nuclear assembly: depletion of TPX2 from Xenopus nuclear assembly extracts produces nuclei ~1/5 the size of controls. TPX2 interacts (by pulldown) with LAP2 (lamina-associated polypeptide 2), and LAP2 localization is disrupted in TPX2-depleted nuclei, suggesting the TPX2-LAP2 interaction is required for proper nuclear reformation. Xenopus egg extract immunodepletion, nuclear assembly assay, size quantification, co-immunoprecipitation/pulldown for TPX2-LAP2 interaction The Journal of cell biology Medium 16735579
2007 TPX2(1-43) binding to Aurora A increases catalytic efficiency by increasing binding affinity for both ATP and peptide substrate. TPX2 binding does not change the reaction mechanism (rapid equilibrium random mechanism) or turnover number. TPX2 binding decreases the size and accessibility of a hydrophobic pocket adjacent to the ATP site, altering inhibitor SAR. In vitro kinase assays with purified proteins, enzyme kinetics (Km/Vmax determination), computer modeling Biochemistry Medium 17705509
2025 TPX2 is lactylated at K249 in HCC tumor tissues; this modification is written by CBP (lactylase) and erased by HDAC1. TPX2 lactylation is required for cell cycle progression and tumor growth. Mechanistically, TPX2 K249 lactylation disrupts PP1 binding to Aurora A, enhances Aurora A T288 phosphorylation, and facilitates cell cycle progression. Mass spectrometry identification of lactylation site, CBP/HDAC1 knockdown, PP1 co-immunoprecipitation, Aurora A pT288 western blot, xenograft tumor models Life science alliance Medium 40107714
2023 TPX2 directly interacts with PXR (pregnane X receptor) by co-immunoprecipitation and enhances PXR transcriptional activation of downstream genes (cyp3a4, MDR-1), promoting sorafenib resistance in HCC cells. Overexpression of TPX2 increases PXR recruitment to the CYP3A4 PXRE/XREM promoter regions. Co-immunoprecipitation, luciferase reporter assay, ChIP assay, qPCR, drug metabolism assays Cell death & disease Medium 36707511

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Molecular cell 517 14580337
2002 Human TPX2 is required for targeting Aurora-A kinase to the spindle. The Journal of cell biology 495 12177045
2000 TPX2, A novel xenopus MAP involved in spindle pole organization. The Journal of cell biology 316 10871281
2020 Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation. Nature communications 183 31937751
2014 TPX2: of spindle assembly, DNA damage response, and cancer. Cellular and molecular life sciences : CMLS 162 24556998
2019 CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR-8075. Journal of cellular physiology 161 30633364
2015 Complementary activities of TPX2 and chTOG constitute an efficient importin-regulated microtubule nucleation module. Nature cell biology 132 26414402
2006 A functional interplay between Aurora-A, Plk1 and TPX2 at spindle poles: Plk1 controls centrosomal localization of Aurora-A and TPX2 spindle association. Cell cycle (Georgetown, Tex.) 123 16418575
2011 TPX2 and AURKA promote 20q amplicon-driven colorectal adenoma to carcinoma progression. Gut 117 22207630
2003 Regulation of Xenopus Aurora A activation by TPX2. The Journal of biological chemistry 117 14701852
2014 Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2. eLife 114 24867643
2004 Characterization of the TPX2 domains involved in microtubule nucleation and spindle assembly in Xenopus egg extracts. Molecular biology of the cell 102 15385625
2012 Tpx2 controls spindle integrity, genome stability, and tumor development. Cancer research 98 22266221
2008 Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes. PloS one 93 18833336
2008 The plant TPX2 protein regulates prospindle assembly before nuclear envelope breakdown. The Plant cell 92 18941054
2017 Structural insight into TPX2-stimulated microtubule assembly. eLife 90 29120325
2014 TPX2 levels modulate meiotic spindle size and architecture in Xenopus egg extracts. The Journal of cell biology 78 25070954
2010 Control of Aurora-A stability through interaction with TPX2. Journal of cell science 74 21147853
2010 The Aurora-A/TPX2 complex: a novel oncogenic holoenzyme? Biochimica et biophysica acta 73 20708655
2017 Structural analysis of the role of TPX2 in branching microtubule nucleation. The Journal of cell biology 71 28264915
2020 Targeting the protein-protein interface pocket of Aurora-A-TPX2 complex: rational drug design and validation. Journal of biomolecular structure & dynamics 69 32448055
2016 Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2. Scientific reports 68 27339427
2008 Spindle pole regulation by a discrete Eg5-interacting domain in TPX2. Current biology : CB 63 18372177
2015 The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC. Annals of oncology : official journal of the European Society for Medical Oncology 61 25632068
2012 Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2. Genes & cancer 60 23634259
2007 Binding of TPX2 to Aurora A alters substrate and inhibitor interactions. Biochemistry 56 17705509
2015 TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT. Digestive diseases and sciences 55 26025609
2012 The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer. Oncology reports 55 22307108
2021 Secretory autophagy-induced bladder tumour-derived extracellular vesicle secretion promotes angiogenesis by activating the TPX2-mediated phosphorylation of the AURKA-PI3K-AKT axis. Cancer letters 52 34597712
2018 TPX2/Aurora kinase A signaling as a potential therapeutic target in genomically unstable cancer cells. Oncogene 50 30177840
2019 Mitotic regulators TPX2 and Aurora A protect DNA forks during replication stress by counteracting 53BP1 function. The Journal of cell biology 49 30602538
2019 TPX2 silencing exerts anti‑tumor effects on hepatocellular carcinoma by regulating the PI3K/AKT signaling pathway. International journal of molecular medicine 48 31638175
2018 Targeting TPX2 suppresses proliferation and promotes apoptosis via repression of the PI3k/AKT/P21 signaling pathway and activation of p53 pathway in breast cancer. Biochemical and biophysical research communications 47 30454896
2013 TPX2 expression is associated with cell proliferation and patient outcome in esophageal squamous cell carcinoma. Journal of gastroenterology 47 23963785
1999 Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display. Genomics 45 10512675
2011 Identification of a TPX2-like microtubule-associated protein in Drosophila. PloS one 44 22140519
2016 Suppression of microtubule assembly kinetics by the mitotic protein TPX2. Journal of cell science 43 26869224
2021 TPX2 mediates prostate cancer epithelial-mesenchymal transition through CDK1 regulated phosphorylation of ERK/GSK3β/SNAIL pathway. Biochemical and biophysical research communications 41 33556637
2015 Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. PloS one 40 25830658
2013 Target protein for Xklp2 (TPX2), a microtubule-related protein, contributes to malignant phenotype in bladder carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 23873098
2020 Aurora A kinase and its activator TPX2 are potential therapeutic targets in KRAS-induced pancreatic cancer. Cellular oncology (Dordrecht, Netherlands) 36 32193808
2019 CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis. Journal of experimental & clinical cancer research : CR 36 31272499
2018 MiR-29a-5p inhibits proliferation and invasion and induces apoptosis in endometrial carcinoma via targeting TPX2. Cell cycle (Georgetown, Tex.) 36 29888640
2017 Targeted TPX2 increases chromosome missegregation and suppresses tumor cell growth in human prostate cancer. OncoTargets and therapy 36 28761362
2017 TPX2-p53-GLIPR1 regulatory circuitry in cell proliferation, invasion, and tumor growth of bladder cancer. Journal of cellular biochemistry 36 28799673
2015 TPX2. Current biology : CB 36 26702647
2015 TPX2 promotes migration and invasion of human breast cancer cells. Asian Pacific journal of tropical medicine 36 26706681
2020 Long non-coding RNA LINC00337 induces autophagy and chemoresistance to cisplatin in esophageal squamous cell carcinoma cells via upregulation of TPX2 by recruiting E2F4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35 32239565
2016 Non-centrosomal TPX2-Dependent Regulation of the Aurora A Kinase: Functional Implications for Healthy and Pathological Cell Division. Frontiers in oncology 34 27148480
2012 Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2. Molecular oncology 34 23333597
2020 CircPOSTN/miR-361-5p/TPX2 axis regulates cell growth, apoptosis and aerobic glycolysis in glioma cells. Cancer cell international 32 32774168
2015 TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule. The Journal of biological chemistry 32 26018074
2015 Positive Surgical Margin, HPV Persistence, and Expression of Both TPX2 and PD-L1 Are Associated with Persistence/Recurrence of Cervical Intraepithelial Neoplasia after Cervical Conization. PloS one 32 26624896
2020 miR-485-3p suppresses colorectal cancer via targeting TPX2. Bratislavske lekarske listy 31 32356447
2009 Expression of TPX2 in salivary gland carcinomas. Oncology reports 31 19148505
2020 The critical role of dysregulated Hh-FOXM1-TPX2 signaling in human hepatocellular carcinoma cell proliferation. Cell communication and signaling : CCS 27 32723329
2021 High nuclear TPX2 expression correlates with TP53 mutation and poor clinical behavior in a large breast cancer cohort, but is not an independent predictor of chromosomal instability. BMC cancer 26 33622270
2020 Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit. Cells 26 32041138
2016 Regulation of Kif15 localization and motility by the C-terminus of TPX2 and microtubule dynamics. Molecular biology of the cell 26 27852894
2012 Targeting protein for xenopus kinesin-like protein 2 (TPX2) regulates γ-histone 2AX (γ-H2AX) levels upon ionizing radiation. The Journal of biological chemistry 26 23045526
2023 TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs. Cell death & disease 25 36707511
2019 TPX2-LIKE PROTEIN3 Is the Primary Activator of α-Aurora Kinases and Is Essential for Embryogenesis. Plant physiology 25 31097675
2013 Upregulation of the TPX2 gene is associated with enhanced tumor malignance of esophageal squamous cell carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 23725757
2021 WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin. The Journal of cell biology 24 34137789
2018 TPX2 level correlates with cholangiocarcinoma cell proliferation, apoptosis, and EMT. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 30257343
2015 TPX2 regulates neuronal morphology through kinesin-5 interaction. Cytoskeleton (Hoboken, N.J.) 23 26257190
2014 TPX2 impacts acetylation of histone H4 at lysine 16: implications for DNA damage response. PloS one 23 25365214
2022 Downregulation of TPX2 impairs the antitumor activity of CD8+ T cells in hepatocellular carcinoma. Cell death & disease 22 35273149
2021 Interaction of spindle assembly factor TPX2 with importins-α/β inhibits protein phase separation. The Journal of biological chemistry 22 34302807
2017 Identification of small molecule inhibitors of the Aurora-A/TPX2 complex. Oncotarget 22 28389630
2023 Therapeutic targeting of the TPX2/TTK network in colorectal cancer. Cell communication and signaling : CCS 21 37770979
2022 KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation. Molecular carcinogenesis 21 36468837
2021 Molecular subtyping and functional validation of TTK, TPX2, UBE2C, and LRP8 in sensitivity of TNBC to paclitaxel. Molecular therapy. Methods & clinical development 21 33665229
2016 TPX2 promotes glioma cell proliferation and invasion via activation of the AKT signaling pathway. Oncology letters 21 28105208
2019 Role of GOLPH3 and TPX2 in Neuroblastoma DNA Damage Response and Cell Resistance to Chemotherapy. International journal of molecular sciences 20 31557970
2014 TPX2 siRNA regulates growth and invasion of esophageal cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 25239289
2011 A novel Aurora kinase A inhibitor MK-8745 predicts TPX2 as a therapeutic biomarker in non-Hodgkin lymphoma cell lines. Leukemia & lymphoma 20 21879811
2009 Plant TPX2 and related proteins. Plant signaling & behavior 20 19704713
2008 TPX2 in malignantly transformed human bronchial epithelial cells by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide. Toxicology 20 18723071
2024 Contribution of AurkA/TPX2 Overexpression to Chromosomal Imbalances and Cancer. Cells 19 39195284
2020 Knockdown of circ_0003340 induces cell apoptosis, inhibits invasion and proliferation through miR-564/TPX2 in esophageal cancer cells. Experimental cell research 19 32535036
2019 HnRNP-F promotes cell proliferation by regulating TPX2 in bladder cancer. American journal of translational research 19 31814907
2023 Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel. OncoTargets and therapy 18 37009264
2014 TPX2 regulates tumor growth in human cervical carcinoma cells. Molecular medicine reports 18 24718984
2012 A novel role for TPX2 as a scaffold and co-activator protein of the Chromosomal Passenger Complex. Cellular signalling 18 22560880
2006 TPX2 is required for postmitotic nuclear assembly in cell-free Xenopus laevis egg extracts. The Journal of cell biology 18 16735579
2016 A TPX2 Proteomimetic Has Enhanced Affinity for Aurora-A Due to Hydrocarbon Stapling of a Helix. ACS chemical biology 17 27775325
2024 Selective Aurora A-TPX2 Interaction Inhibitors Have In Vivo Efficacy as Targeted Antimitotic Agents. Journal of medicinal chemistry 16 39190548
2023 AurkA nuclear localization is promoted by TPX2 and counteracted by protein degradation. Life science alliance 16 36797043
2023 PP6 regulation of Aurora A-TPX2 limits NDC80 phosphorylation and mitotic spindle size. The Journal of cell biology 16 36897279
2021 A guide to plant TPX2-like and WAVE-DAMPENED2-like proteins. Journal of experimental botany 16 33130902
2021 Importin α phosphorylation promotes TPX2 activation by GM130 to control astral microtubules and spindle orientation. Journal of cell science 16 33526712
2019 Overexpression of CDCA5, KIF4A, TPX2, and FOXM1 Coregulated Cell Cycle and Promoted Hepatocellular Carcinoma Development. Journal of computational biology : a journal of computational molecular cell biology 16 31593490
2018 TPX2 promotes cell proliferation and migration via PLK1 in OC. Cancer biomarkers : section A of Disease markers 16 29865033
2025 TPX2 lactylation is required for the cell cycle regulation and hepatocellular carcinoma progression. Life science alliance 15 40107714
2019 MiR-491 suppresses migration and invasion via directly targeting TPX2 in breast cancer. European review for medical and pharmacological sciences 15 31799669
2015 Phosphorylation of targeting protein for Xenopus kinesin-like protein 2 (TPX2) at threonine 72 in spindle assembly. The Journal of biological chemistry 15 25688093
2014 TPX2 overexpression in medullary thyroid carcinoma mediates TT cell proliferation. Pathology oncology research : POR 15 24488334
2011 Two TPX2-dependent switches control the activity of Aurora A. PloS one 14 21347367
2014 HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma. OncoTargets and therapy 13 24966688

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