Affinage

KIF18A

Kinesin-like protein KIF18A · UniProt Q8NI77

Audit flag: ungrounded claim
Length
898 aa
Mass
102.3 kDa
Annotated
2026-06-10
74 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF18A is a plus-end-directed kinesin-8 motor that governs mitotic chromosome alignment by suppressing the dynamics of kinetochore microtubule plus-ends (PMID:17346968, PMID:18267093, PMID:20153196). Its N-terminal motor domain promotes microtubule pausing and growth suppression in a concentration-dependent manner rather than acting as a pure depolymerizer (PMID:20153196, PMID:22595673), while a second ATP-independent microtubule-binding site in its C-terminal tail tethers the motor to the lattice, conferring the high processivity required for accumulation at kinetochore microtubule plus-ends and for damping chromosome oscillations (PMID:21884977, PMID:22102900). A relatively long neck linker allows KIF18A to bypass microtubule-associated protein obstacles and reach plus-ends at the spindle center (PMID:30655363). KIF18A activity is spatiotemporally tuned: Cdk1 imposes inhibitory phosphorylation and PP1 (recruited via an RVxF motif to PP1γ) dephosphorylates and activates the motor upon biorientation (PMID:25048371, PMID:25281536, PMID:39610707), kinesin-binding protein buffers motor output by blocking microtubule engagement (PMID:30709852), and HURP modulates processivity in a concentration-dependent fashion (PMID:21924616, PMID:39516196). Functionally, KIF18A cooperates with CENP-E and BubR1 to drive chromosome congression (PMID:19625775, PMID:41218610), and its loss triggers spindle assembly checkpoint activation through loss of kinetochore tension even at properly attached kinetochores (PMID:30122526). This dependency underlies the selective vulnerability of chromosomally unstable cancer cells, which arrest upon KIF18A inhibition because of weak basal APC/C activity and persistent SAC signaling (PMID:38279026, PMID:40596795), a vulnerability exploited by ATP-noncompetitive inhibitors that bind the KIF18A-tubulin interface defined by crystal structures (PMID:35286090, PMID:39747049, PMID:41257005).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2007 High

    Established KIF18A as a plus-end-directed kinesin with length-dependent microtubule depolymerizing activity whose loss disrupts spindle length and chromosome congression, defining its core mitotic role.

    Evidence in vitro motility/depolymerization assays plus RNAi and live-cell imaging

    PMID:17346968

    Open questions at the time
    • Did not resolve whether the dominant in vivo activity is depolymerization vs. dynamics suppression
    • Mechanism of plus-end accumulation unknown
  2. 2008 High

    Reframed KIF18A as a suppressor of chromosome movements through motor-dependent gradient accumulation on kinetochore microtubules, rather than a simple depolymerizer.

    Evidence quantitative kinetochore tracking with RNAi and gradient imaging

    PMID:18267093

    Open questions at the time
    • Biochemical distinction from depolymerization not yet resolved
    • Tail contribution to gradient unclear
  3. 2010 High

    Showed KIF18A dampens plus-end polymerization dynamics without destabilizing microtubules, distinguishing its biochemistry from the depolymerizing yeast ortholog Kip3.

    Evidence in vitro microtubule dynamics assays with live-cell validation

    PMID:20153196

    Open questions at the time
    • Single-lab in vitro characterization
    • Did not define the molecular basis of pausing
  4. 2011 High

    Resolved the structural division of labor: the C-terminal tail provides an ATP-independent, lattice-diffusing microtubule-binding site essential for processivity and plus-end accumulation, while the N-terminal motor confers growth suppression.

    Evidence domain/truncation/point mutants, single-molecule motility, co-pelleting, in-cell rescue (multiple concurrent studies)

    PMID:21884977 PMID:21885282 PMID:22102900

    Open questions at the time
    • Did not establish how spindle-length control is separated from chromosome positioning at the molecular level
    • Regulation of tail engagement unknown
  5. 2012 High

    Demonstrated by reconstitution that purified KIF18A directly promotes microtubule pausing in a concentration-dependent manner, providing the dominant mechanism for confining centromeres to the spindle midzone.

    Evidence reconstituted dynamic microtubule assays with purified protein plus live-cell imaging

    PMID:22595673

    Open questions at the time
    • Did not address how pausing activity is regulated in vivo
    • Role of accessory factors not tested
  6. 2010 Medium

    Identified CENP-E and BubR1 as physical partners and showed KIF18A loss destabilizes CENP-E protein, linking KIF18A function to congression machinery; KO mice revealed germ-cell aplasia from mitotic and meiotic congression failure.

    Evidence reciprocal Co-IP, RNAi, rescue, and Kif18a knockout mice

    PMID:19625775 PMID:20981276

    Open questions at the time
    • Direct vs. indirect basis of CENP-E/BubR1 destabilization not fully resolved
    • Co-IP without structural mapping of interfaces
  7. 2011 Medium

    Showed HURP binds KIF18A and modulates its localization and dynamics at kinetochore microtubule plus-ends, introducing a MAP-based layer of regulation.

    Evidence Co-IP, BiFC, live-cell imaging, rescue experiments

    PMID:21924616

    Open questions at the time
    • Mechanism of modulation not defined at this stage
    • Single-lab interaction data
  8. 2014 High

    Defined antagonistic Cdk1/PP1 control of KIF18A, with PP1γ docking via an RVxF motif and dephosphorylation activating the motor upon biorientation, explaining temporal switching from oscillation to plate thinning.

    Evidence MS phosphosite mapping, kinase/phosphatase perturbation, biochemical RVxF-binding assays

    PMID:25048371 PMID:25281536

    Open questions at the time
    • RVxF interaction shown by single-method binding assay
    • Full phosphosite-to-function map incomplete
  9. 2015 Medium

    Identified SUMO2 modification of KIF18A peaking at metaphase as a regulator of mitotic exit timing and BubR1 dissociation, adding a post-translational control independent of stability or localization.

    Evidence His6-SUMO2 pull-down, acceptor-lysine mutagenesis, time-lapse imaging

    PMID:25884224

    Open questions at the time
    • SUMO E3 ligase not identified
    • Mechanistic link to BubR1 dissociation unresolved
  10. 2018 High

    Established that lethality on KIF18A loss arises from SAC activation at attached-but-tensionless kinetochores rather than missegregation per se, clarifying the basis of essentiality.

    Evidence haploid genetic screen, SAC-null epistasis, tension measurements, live imaging

    PMID:30122526

    Open questions at the time
    • Did not yet define why CIN cells are selectively sensitive
    • Tension-sensing pathway link incomplete
  11. 2019 High

    Defined two mechanical determinants of targeting: KBP buffers motor activity by blocking microtubule binding, and a long neck linker enables navigation past MAP obstacles to reach K-fiber plus-ends.

    Evidence gliding/co-pelleting inhibition assays and single-molecule assays on MAP-coated microtubules with in-cell imaging

    PMID:30655363 PMID:30709852

    Open questions at the time
    • Physiological contexts that engage KBP regulation in vivo not fully mapped
    • Single-lab studies
  12. 2023 Medium

    Showed neck-linker phosphorylation (S357) biases KIF18A toward kinetochore vs. peripheral microtubules, linking a phosphosite to subpopulation selection and spindle positioning.

    Evidence phosphomimetic and short-neck-linker mutants with live-cell spindle positioning assays

    PMID:37903223

    Open questions at the time
    • Responsible kinase not identified
    • Single-lab functional study
  13. 2024 High

    Explained the selective lethality of KIF18A inhibition: it broadly raises SAC signaling, and arrest occurs only in cells with weak basal APC/C activity, placing KIF18A in an APC/C-dependent mitotic-exit network.

    Evidence APC/C reporters, SAC/APC/C perturbation across a cancer cell line panel; APC subunit epistasis

    PMID:38279026 PMID:40596795

    Open questions at the time
    • Quantitative threshold of APC/C activity defining sensitivity not delineated
    • Direct molecular link between KIF18A and APC/C subunits unresolved
  14. 2024 High

    Resolved the HURP-KIF18A interplay biophysically: HURP activates KIF18A at low density but sterically blocks the motor at high density, with the two together suppressing plus-end dynamics more than either alone.

    Evidence single-molecule imaging and cryo-EM of the HURP-microtubule complex

    PMID:39516196

    Open questions at the time
    • In vivo concentration regimes governing the switch not measured
    • Spatial distribution of HURP on K-fibers not mapped
  15. 2025 High

    Crystal structures of the KIF18A-tubulin complex defined an ATP-noncompetitive, microtubule-dependent allosteric inhibitor-binding site at the tubulin interface, enabling structure-based inhibitor design validated in xenografts.

    Evidence X-ray crystallography, ATPase and gliding assays, photoaffinity labeling, in vivo tumor models

    PMID:35286090 PMID:39747049 PMID:41257005

    Open questions at the time
    • Resistance mechanisms to interface inhibitors not characterized
    • Allosteric coupling to the catalytic cycle not fully described
  16. 2025 Medium

    Extended KIF18A function beyond metaphase, showing it is required for central spindle organization and centralspindlin (KIF23/RACGAP1) localization during cytokinesis, and confirmed cooperation with CENP-E downstream of CENP-C in early prometaphase.

    Evidence siRNA depletion with centralspindlin immunofluorescence; genome-wide CENP-C synthetic-lethality screen

    PMID:39954259 PMID:41218610

    Open questions at the time
    • Direct vs. indirect role in centralspindlin recruitment unresolved
    • Molecular basis of the CENP-C/CENP-E coupling not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KIF18A integrates its multiple regulatory inputs (Cdk1/PP1 phosphorylation, SUMOylation, KBP buffering, HURP density, neck-linker phosphorylation) into a single spatiotemporal output at the kinetochore remains unresolved.
  • No unified quantitative model linking the regulatory layers
  • Relative in vivo contribution of each modifier unquantified
  • Structural basis of tail-mediated tethering on dynamic K-fibers not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0140657 ATP-dependent activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005856 cytoskeleton 3
Pathway
R-HSA-1640170 Cell Cycle 4
Partners
BUBR1CENP-EESR1HURPKBPPP1ΓTTC3

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 KIF18A is a slow plus-end-directed kinesin with microtubule depolymerizing activity in vitro, and depolymerizes longer microtubules more quickly than shorter ones (length-dependent depolymerization). In vivo, KIF18A localizes near plus-ends of kinetochore microtubules; its depletion causes aberrantly long mitotic spindles, loss of tension across sister kinetochores, Mad2-dependent spindle assembly checkpoint activation, and chromosome congression failure. RNAi depletion, in vitro biochemical motility and depolymerization assays, live-cell microscopy Current biology : CB High 17346968
2008 KIF18A accumulates as a gradient on kinetochore microtubules in a motor-activity-dependent manner and suppresses chromosome oscillation amplitude and slows poleward movement during anaphase, establishing its primary role as a suppressor of chromosome movements rather than a depolymerizer per se. RNAi knockdown, quantitative live-cell imaging of kinetochore movements, fluorescence imaging of KIF18A gradient Developmental cell High 18267093
2010 KIF18A inhibits the polymerization dynamics (dynamicity) of microtubule plus ends without destabilizing them in interphase cells, distinguishing its biochemical activity from the budding yeast ortholog Kip3, which depolymerizes microtubules. In vitro microtubule dynamics assays, live-cell imaging of microtubule plus-end dynamics Current biology : CB High 20153196
2011 KIF18A's C-terminal tail domain contains a second microtubule-binding site that diffuses along the microtubule lattice, tethering the motor and enhancing processivity; this tail-mediated processivity is required for accumulation at kinetochore microtubule plus-ends and for suppression of chromosome movements. The N-terminal motor domain confers microtubule growth suppression activity. Kif18A tail-deletion and point mutants, single-molecule motility assays, live-cell imaging, microtubule co-pelleting Molecular cell High 21884977
2011 An ATP-independent microtubule-binding site in the C-terminal tail (C-proximal 121 residues) of KIF18A is essential for its high processivity (single-molecule measurements) and for plus-end accumulation at kinetochore microtubules; removing this domain abolishes mitotic function. C-terminal truncation mutants, single-molecule processivity measurements, in vitro MT binding, cell imaging PloS one High 22102900
2011 KIF18A controls spindle length independently of chromosome positioning. The C-terminal ATP-independent MT-binding site has strong affinity for microtubules in vitro and in cells; computational modeling predicts that fast motility and low off-rate from MT ends are both important for KIF18A function. Spindle-length measurements after KIF18A domain mutant expression, in vitro MT co-sedimentation, computational modeling Current biology : CB Medium 21885282
2012 KIF18A directly promotes microtubule pausing in a concentration-dependent manner using reconstituted dynamic microtubule assays, providing the dominant mechanism for restricting centromere movement to the spindle midzone. Reconstituted dynamic microtubule assays with purified KIF18A, quantitative live-cell imaging Developmental cell High 22595673
2009 KIF18A physically interacts with CENP-E and BubR1 during mitosis (co-immunoprecipitation). KIF18A depletion causes specific protein degradation of CENP-E (not transcriptional reduction), and the resulting CENP-E loss partially mediates chromosome congression defects. Co-immunoprecipitation, RNAi, rescue with wild-type vs. mutant CENP-E tail domain Cell cycle (Georgetown, Tex.) Medium 19625775
2010 KIF18A physically interacts with BubR1 and CENP-E; interaction is modulated during mitosis. KIF18A deficiency causes degradation of CENP-E and BubR1, microtubule dynamics perturbation, spindle pole integrity loss, and apoptosis; in male mice, KIF18A knockout leads to germinal cell aplasia due to impaired chromosome congression in mitosis and meiosis. Kif18a knockout mice, RNAi in GC-1 and HeLa cells, co-immunoprecipitation, histology Genes & cancer Medium 20981276
2011 HURP interacts with KIF18A (co-immunoprecipitation and bimolecular fluorescence complementation), regulates KIF18A localization and dynamics at K-MT plus-ends, and overexpression of the HURP microtubule-binding domain causes mitotic defects mimicking KIF18A depletion that are partially rescued by KIF18A overexpression. Co-immunoprecipitation, bimolecular fluorescence complementation (BiFC), live-cell imaging, rescue experiments Current biology : CB Medium 21924616
2014 KIF18A is antagonistically regulated by Cdk1-mediated inhibitory phosphorylation (promoting chromosome oscillations in early metaphase) and PP1 (dephosphorylating KIF18A to promote metaphase plate thinning). PP1α/γ is recruited to kinetochores upon chromosome biorientation, tipping the balance toward active, dephosphorylated KIF18A. Kinase/phosphatase perturbation, mass spectrometry phosphosite identification, RNAi, live-cell imaging Nature communications High 25048371
2014 KIF18A directly interacts with PP1γ through a conserved RVxF motif in its sequence; this interaction is broadly conserved across kinesins, suggesting an ancestral PP1 docking function. Biochemical interaction assays, phylogenetic analysis of RVxF motif conservation Biochemical and biophysical research communications Medium 25281536
2015 KIF18A is covalently modified by SUMO2, peaking at metaphase and decreasing at anaphase onset. Multiple lysine residues (K148, K442, K533, K660, K683) are SUMO2 acceptors. SUMO-resistant KIF18A mutants do not affect protein stability or localization but cause delayed mitotic exit and compromised BubR1 dissociation from kinetochores after anaphase onset. His6-SUMO2 pull-down, site-directed mutagenesis, confocal time-lapse imaging, immunofluorescence BMC cancer Medium 25884224
2018 Loss of KIF18A results in spindle assembly checkpoint (SAC) activation at kinetochores that have established fully functional kinetochore-microtubule attachments but lack tension; this SAC activation (not chromosome missegregation per se) is the cause of lethality in cells without KIF18A. Haploid genetic screen (HAP1 cells), SAC-deficient double mutants, live-cell imaging, tension measurements Current biology : CB High 30122526
2019 Kinesin-binding protein (KBP) directly inhibits KIF18A motor activity by preventing microtubule binding (gliding filament and microtubule co-pelleting assays), reducing KIF18A's mitotic localization; KBP overexpression phenocopies KIF18A/KIF15 co-depletion, and KBP depletion causes lagging chromosomes mimicking KIF18A overexpression. Gliding filament assay, microtubule co-pelleting, overexpression/depletion, live-cell imaging The Journal of cell biology High 30709852
2019 KIF18A's relatively long neck linker is required for its accumulation at plus-ends of kinetochore microtubules at the spindle center; shorter neck linker (sNL) variants are deficient in navigating microtubule-associated protein obstacles on K-fibers, as demonstrated by single-molecule assays showing reduced proficiency at bypassing MAP-coated microtubules. Neck linker length mutants, single-molecule assays on MAP-coated microtubules, live-cell imaging Life science alliance High 30655363
2011 Microtubule stabilization (taxol treatment or Aurora B inhibitor-induced end stabilization) triggers rapid KIF18A plus-end accumulation independent of kinetochore association, suggesting that MT plus-end stability controls KIF18A localization. Pharmacological stabilization (taxol, Aurora B inhibitor), live-cell imaging of KIF18A localization Cell structure and function Medium 22104080
2007 KIF18A (MS-KIF18A) interacts with estrogen receptor alpha (ERα, both 66 and 46 kDa isoforms) as demonstrated by immunoprecipitation in MBA-15 osteogenic cells and ectopic co-expression in COS-7 cells; 17β-estrogen challenge induces association of KIF18A with phospho-ERK1/2, which is disrupted by ICI-182,780 or the MAPK inhibitor PD98059. Co-immunoprecipitation, ectopic expression, pharmacological inhibitors Journal of cellular biochemistry Low 17006958
2009 ERα is a cargo of KIF18A; pull-down assay with recombinant proteins confirms direct interaction between KIF18A and ERα in vitro. Estrogen stimulates KIF18A promoter activity (luciferase reporter) via ERα and c-Jun binding to the KIF18A promoter (ChIP assay). In vitro pull-down, luciferase reporter assay, ChIP assay PloS one Low 19636373
2018 In mouse oocyte meiosis, Kif18A knockdown increases acetylated tubulin levels and decreases Sirt2 (tubulin deacetylase) expression, causing spindle organization defects and chromosome misalignment; microinjection of tubulin K40R mRNA (preventing acetylation) rescues spindle morphology in Kif18A-knockdown oocytes. Morpholino/siRNA knockdown in mouse oocytes, tubulin acetylation immunofluorescence, mRNA microinjection rescue Cell division Medium 30459823
2021 Micronuclei formed in KIF18A KO cells recruit increased nuclear envelope components and support successful chromatin decondensation (stable nuclear envelopes), unlike micronuclei induced by nocodazole or radiation; lagging chromosomes in KIF18A KO cells are positioned closer to main chromatin masses. KIF18A KO cell lines, live-cell imaging, nuclear envelope component immunofluorescence, Trp53 deletion mouse model The Journal of cell biology Medium 34515734
2023 KIF18A inhibitors (photoaffinity labeling experiments) bind at the interface of KIF18A and tubulin, identifying a tubulin-KIF18A interface as a druggable allosteric site distinct from the ATP-binding pocket. Photoaffinity labeling, medicinal chemistry, in vivo mitotic arrest assays Journal of medicinal chemistry Medium 35286090
2024 KIF18A inhibition drives a widespread increase in spindle assembly checkpoint (SAC) signaling; whether cells arrest depends on APC/C activity. Cells with weak basal APC/C activity and/or persistent SAC signaling are uniquely sensitive to KIF18A inhibition, explaining the selective lethality in CIN cancer cells. Live-cell imaging, APC/C activity reporters, genetic/pharmacological perturbation of SAC and APC/C, panel of cancer cell lines The EMBO journal High 38279026
2024 HURP regulates KIF18A motility in a concentration-dependent manner: sparse HURP decoration activates KIF18A motility, while high HURP concentrations hinder processive motility by steric exclusion at the KIF18A motor domain-microtubule binding site. HURP and KIF18A together suppress microtubule plus-end dynamics more effectively than either alone. Single-molecule imaging in vitro, cryo-EM structure of HURP-microtubule complex Nature communications High 39516196
2024 KIF18A directly binds TTC3 and enhances TTC3-p-AKT interaction, promoting TTC3-mediated ubiquitination and degradation of phospho-AKT, thereby suppressing the AKT/mTOR pathway in hepatic stellate cells. Co-immunoprecipitation, ubiquitination assay, KIF18A knockdown/overexpression in vitro and in CCl4 mouse liver fibrosis model Cellular and molecular life sciences : CMLS Medium 38372748
2023 Phosphomimetic mutation S357D in the neck-linker of KIF18A redirects the motor from kinetochore microtubules to non-kinetochore peripheral microtubules, causing spindle positioning defects and failure to promote mitotic progression; this phenotype is mimicked by a shortened neck-linker mutant. Phosphomimetic mutagenesis, live-cell imaging, spindle positioning assays Molecular biology of the cell Medium 37903223
2024 Mutation of S284 within the alpha-4 helix of KIF18A causes relocalization from K-fiber plus-ends to spindle poles, loss of KIF18A function, and failure to support CIN tumor cell proliferation. Small molecules predicted to interact with the alpha-4 helix produce similar relocalization and functional loss. Site-directed mutagenesis, live-cell imaging, small-molecule inhibitor treatment, CIN cell proliferation assay Frontiers in molecular biosciences Medium 38410188
2024 Chromosome alignment and KIF18A plus-end localization depend on a spindle-localized fraction of inhibited/inactive Cdk1 (i-Cdk1, Wee1-phosphorylated). Reducing i-Cdk1 causes spindle defects and poor KIF18A localization; restoring i-Cdk1 reverses both; expressing a phosphonull KIF18A at Cdk1 phosphorylation sites rescues alignment defects in i-Cdk1-depleted cells. Genetic perturbation of Wee1/Cdk1 phosphorylation, immunofluorescence, cell fractionation, phosphonull KIF18A rescue Frontiers in cell and developmental biology Medium 39610707
2025 KIF18A depletion disrupts the parallel structure of the central spindle in late anaphase, causing mislocalization of the centralspindlin components KIF23 (MKLP1) and RACGAP1, impaired cleavage furrow establishment, and incomplete cytokinesis. KIF18A localizes at the metaphase plate, then central spindle in late anaphase, then spindle midbody in telophase. siRNA depletion, live-cell imaging, immunofluorescence of centralspindlin components The FEBS journal Medium 39954259
2025 Genetic epistasis screen using a hypomorphic CENP-C mutant identified KIF18A as synthetic lethal; the synthetic defect is due to reduced CENP-E function in the CENP-C mutant background. KIF18A promotes chromosome alignment in cooperation with CENP-E downstream of CENP-C during early prometaphase. Genome-wide Cas9-based functional genetics screen, synthetic lethality epistasis, CENP-E functional analysis Cell reports Medium 41218610
2024 Depletion of KIF18A induced mitotic arrest in cells, which was partially rescued by co-depletion of ANAPC7 (APC7) and exacerbated by co-depletion of ANAPC5 (APC5), placing KIF18A in a regulatory network with APC/C subunits controlling mitotic exit. RNAi double-depletion epistasis in cell lines, mitotic arrest quantification Scientific reports Medium 40596795
2025 A crystal structure of the KIF18A-tubulin complex was determined, supporting structure-based inhibitor design. The ATP non-competitive inhibitor VLS-1272 is microtubule-dependent, blocks KIF18A ATPase activity, prevents KIF18A translocation across the mitotic spindle, and results in chromosome congression defects, mitotic cell accumulation, and cell death. Crystal structure of KIF18A-tubulin complex, ATPase assays, microtubule gliding assays, in vivo xenograft Nature communications High 39747049
2025 A high-resolution crystal structure of the KIF18A-tubulin complex was obtained; ATX020 binds at the KIF18A-tubulin interface in an experimentally guided model, confirming the tubulin interface as a druggable allosteric site. X-ray crystallography of KIF18A-tubulin complex, structure-based drug design ACS medicinal chemistry letters High 41257005
2020 KIF18A mRNA stability in esophageal cancer cells is regulated post-transcriptionally by the RNA-binding protein IGF2BP3, which binds KIF18A mRNA (RIP assay) and increases its stability. RNA immunoprecipitation (RIP), RNA stability assay, siRNA knockdown Biochemical and biophysical research communications Low 33872988
2020 KIF18A mRNA in human male germ cells (TCam-2 line) is post-transcriptionally repressed by PUM1 and PUM2 proteins via PUM-binding elements in KIF18A's 3'-UTR; PUM repression of KIF18A reduces proliferation and alters the cell cycle in TCam-2 cells. RNA co-immunoprecipitation, luciferase reporter assay with wild-type and mutant KIF18A 3'-UTR, siRNA knockdown, flow cytometry Journal of cell science Medium 32094263
2025 The JNK1/c-Jun signaling pathway directly activates KIF18A transcription: c-Jun binds and activates the KIF18A promoter (ChIP and luciferase reporter assays); JNK1 inhibition decreases KIF18A expression and c-Jun phosphorylation; c-Jun knockdown inhibits cervical cancer growth partially rescued by KIF18A overexpression. ChIP assay, luciferase reporter assay, JNK1 inhibition, c-Jun siRNA, KIF18A rescue Journal of cellular physiology Medium 39749722

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Developmental cell 266 18267093
2007 The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression. Current biology : CB 256 17346968
2010 The kinesin-8 Kif18A dampens microtubule plus-end dynamics. Current biology : CB 139 20153196
2012 Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension. Developmental cell 135 22595673
2021 Chromosomally unstable tumor cells specifically require KIF18A for proliferation. Nature communications 108 33619254
2011 A tethering mechanism controls the processivity and kinetochore-microtubule plus-end enrichment of the kinesin-8 Kif18A. Molecular cell 106 21884977
2010 Kif18A is involved in human breast carcinogenesis. Carcinogenesis 93 20595236
2011 Kif18A uses a microtubule binding site in the tail for plus-end localization and spindle length regulation. Current biology : CB 91 21885282
2024 KIF18A inactivates hepatic stellate cells and alleviates liver fibrosis through the TTC3/Akt/mTOR pathway. Cellular and molecular life sciences : CMLS 77 38372748
2011 A non-motor microtubule binding site is essential for the high processivity and mitotic function of kinesin-8 Kif18A. PloS one 64 22102900
2014 Pre-anaphase chromosome oscillations are regulated by the antagonistic activities of Cdk1 and PP1 on Kif18A. Nature communications 57 25048371
2015 Kif18a is specifically required for mitotic progression during germ line development. Developmental biology 53 25824710
2023 Small-molecule inhibition of kinesin KIF18A reveals a mitotic vulnerability enriched in chromosomally unstable cancers. Nature cancer 51 38151625
2018 The role of kinesin KIF18A in the invasion and metastasis of hepatocellular carcinoma. World journal of surgical oncology 49 29466986
2020 Knockdown of Circ_CCNB2 Sensitizes Prostate Cancer to Radiation Through Repressing Autophagy by the miR-30b-5p/KIF18A Axis. Cancer biotherapy & radiopharmaceuticals 44 32716640
2009 Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E. Cell cycle (Georgetown, Tex.) 40 19625775
2011 HURP regulates chromosome congression by modulating kinesin Kif18A function. Current biology : CB 39 21924616
2010 Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E. Genes & cancer 39 20981276
2018 Loss of Kif18A Results in Spindle Assembly Checkpoint Activation at Microtubule-Attached Kinetochores. Current biology : CB 30 30122526
2021 KIF18A knockdown reduces proliferation, migration, invasion and enhances radiosensitivity of esophageal cancer. Biochemical and biophysical research communications 27 33872988
2018 Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+ breast cancer. Breast cancer research and treatment 25 30306428
2024 Weakened APC/C activity at mitotic exit drives cancer vulnerability to KIF18A inhibition. The EMBO journal 24 38279026
2021 Micronuclei in Kif18a mutant mice form stable micronuclear envelopes and do not promote tumorigenesis. The Journal of cell biology 24 34515734
2022 Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe. Journal of medicinal chemistry 23 35286090
2019 Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15. The Journal of cell biology 23 30709852
2013 Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC) tumors in mice through impairing Akt phosphorylation. Biochemical and biophysical research communications 23 23872115
2018 Kif18a regulates Sirt2-mediated tubulin acetylation for spindle organization during mouse oocyte meiosis. Cell division 22 30459823
2014 The human mitotic kinesin KIF18A binds protein phosphatase 1 (PP1) through a highly conserved docking motif. Biochemical and biophysical research communications 22 25281536
2019 Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo. Disease markers 20 31772692
2005 MS-KIF18A, new kinesin; structure and cellular expression. Gene 18 15878648
2019 Expression of KIF18A Is Associated with Increased Tumor Stage and Cell Proliferation in Prostate Cancer. Medical science monitor : international medical journal of experimental and clinical research 16 31451680
2025 Targeting chromosomally unstable tumors with a selective KIF18A inhibitor. Nature communications 15 39747049
2019 KIF18A's neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle. Life science alliance 14 30655363
2024 KIF18A inhibition: the next big player in the search for cancer therapeutics. Cancer metastasis reviews 13 39580563
2023 KIF18A improves migration and invasion of colorectal cancer (CRC) cells through inhibiting PTEN signaling. Aging 13 37708299
2020 Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus. Journal of cellular and molecular medicine 13 32253833
2007 MS-KIF18A, a kinesin, is associated with estrogen receptor. Journal of cellular biochemistry 11 17006958
2015 Sumoylation of Kif18A plays a role in regulating mitotic progression. BMC cancer 10 25884224
2009 The regulation of MS-KIF18A expression and cross talk with estrogen receptor. PloS one 10 19636373
2008 New insights on cellular distribution, microtubule interactions and post-translational modifications of MS-KIF18A. Journal of cellular physiology 10 18680169
2023 KIF18A interacts with PPP1CA to promote the malignant development of glioblastoma. Experimental and therapeutic medicine 9 36911368
2024 Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells. Frontiers in molecular biosciences 7 38410188
2019 KIF18A promotes head and neck squamous cell carcinoma invasion and migration via activation of Akt signaling pathway. Translational cancer research 7 35116978
2011 Microtubule stabilization triggers the plus-end accumulation of Kif18A/kinesin-8. Cell structure and function 7 22104080
2024 Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and β-catenin in infiltrating breast carcinoma of no special type. World journal of surgical oncology 6 38195458
2021 Relevance of aneuploidy for cancer therapies targeting the spindle assembly checkpoint and KIF18A. Molecular & cellular oncology 6 34027049
2024 Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma. Digestive diseases and sciences 5 38446308
2024 Exploration of inhibitors targeting KIF18A with ploidy-specific lethality. Drug discovery today 5 39168405
2020 Kinesin KIF18A is a novel PUM-regulated target promoting mitotic progression and survival of a human male germ cell line. Journal of cell science 5 32094263
2019 Kinesin family member KIF18A is a critical cellular factor that regulates the differentiation and activation of dendritic cells. Genes & genomics 5 31677127
2025 KIF18A Is a Novel Target of JNK1/c-Jun Signaling Pathway Involved in Cervical Tumorigenesis. Journal of cellular physiology 4 39749722
2023 Modification of the neck-linker of KIF18A alters Microtubule subpopulation preference. Molecular biology of the cell 4 37903223
2025 Kinesin-like protein KIF18A is required for faithful coordination of chromosome congression with cytokinesis. The FEBS journal 3 39954259
2024 KIF18A promotes cervical squamous cell carcinoma progression by activating the PI3K/AKT pathway through upregulation of CENPE. Cancer biomarkers : section A of Disease markers 3 39331093
2024 HURP regulates Kif18A recruitment and activity to synergistically control microtubule dynamics. Nature communications 3 39516196
2025 Targeting KIF18A triggers antitumor immunity and enhances efficiency of PD-1 blockade in colorectal cancer with chromosomal instability phenotype. Cell death discovery 2 40175357
2025 Discovery of Kinesin KIF18A Inhibitor ATX020: Tactical Application of Silicon Atom Replacement. ACS medicinal chemistry letters 2 41257005
2024 Molecular interplay between HURP and Kif18A in mitotic spindle regulation. bioRxiv : the preprint server for biology 2 38645125
2024 Chromosome alignment and Kif18A action rely on spindle-localized control of Cdk1 activity. Frontiers in cell and developmental biology 2 39610707
2020 Preliminary study on the clinical significance of kinesin Kif18a in nonsmall cell lung cancer: An analysis of 100 cases. Medicine 2 31977917
2026 KIF18A inhibition and its rising role in cancer therapy trials: from bench to bedside. Expert opinion on investigational drugs 1 41543111
2025 Deciphering the Role of KIF18A in Osteosarcoma Progression: An Integrative Analysis and Experimental Validation. Frontiers in bioscience (Landmark edition) 1 41198558
2025 KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C. Cell reports 1 41218610
2024 Anapc5 and Anapc7 as genetic modifiers of KIF18A function in fertility and mitotic progression. bioRxiv : the preprint server for biology 1 39677807
2023 Modification of the Neck Linker of KIF18A Alters Microtubule Subpopulation Preference. bioRxiv : the preprint server for biology 1 37205510
2026 Loss of JAK1 Function Causes G2-M Cell-Cycle Defects Vulnerable to KIF18A Inhibition. Cancer research 0 41591363
2026 Investigation of ELF5, KIF18A, NPTX1 and COL23A1 genes in the pathophysiology of indirect inguinal hernia in children. Pediatric surgery international 0 41925903
2026 KIF18A Maintains Kinetochore-Microtubule Attachments in CIN Cells by Limiting Microtubule Polymerization. bioRxiv : the preprint server for biology 0 42039568
2025 Loss of JAK1 Function Causes G2/M Cell Cycle Defects Vulnerable to Kif18a Inhibition. bioRxiv : the preprint server for biology 0 40060568
2025 Anapc5 and Anapc7 as genetic modifiers of KIF18A function in fertility and mitotic progression. Scientific reports 0 40596695
2025 KIF18A induces the EMT process of hepatoma cells through the 5-LOX-dependent arachidonic acid pathway. PloS one 0 41082523
2025 The KIF18A Inhibitor ATX020 Induces Mitotic Arrest and DNA Damage in Chromosomally Instable High-Grade Serous Ovarian Cancer Cells. Cells 0 41369352
2024 Molecular interplay between HURP and Kif18A in mitotic spindle regulation. Research square 0 38854046
2023 Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells. bioRxiv : the preprint server for biology 0 37905069

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