Affinage

KIF15

Kinesin-like protein KIF15 · UniProt Q9NS87

Length
1388 aa
Mass
160.2 kDa
Annotated
2026-04-28
66 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF15 (kinesin-12) is a plus-end-directed, processive homotetrameric motor that crosslinks and slides antiparallel microtubules to drive bipolar spindle assembly in cooperation with Eg5, and maintains kinetochore-fiber mechanical integrity during mitosis (PMID:19818618, PMID:24668168, PMID:34668719). KIF15 is autoinhibited by its C-terminal domain and activated by simultaneous engagement of two microtubules, which triggers its selective accumulation on bundled kinetochore fibers independently of TPX2; TPX2 instead modulates KIF15 localization and inhibits its stepping, while kinesin-binding protein (KBP) buffers KIF15 activity by blocking microtubule binding (PMID:25264249, PMID:27852894, PMID:30709852). Beyond mitosis, KIF15 recruits deubiquitinases (USP14, USP10, USP15) or modulates E3 ligases (MDM2) to stabilize diverse client proteins including AR/AR-V7, PGK1, DEK, and NRAS, and it regulates tubulin acetylation by recruiting HDAC6, SIRT2, and NAT10 to spindle microtubules in oocytes (PMID:33277366, PMID:36807568, PMID:34280614, PMID:35835966). In neurons, KIF15 limits microtubule sliding to restrain axon elongation and transports PSD95 to dendritic spines to maintain excitatory postsynaptic scaffolding; KIF15-knockout mice display reduced spine density, excitatory synapse loss, and mood disorder-like behavior (PMID:30411440, PMID:40892874).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 Medium

    Identifying KIF15 as a mitotic chromosome-peripheral kinesin established that it is a phosphorylation-regulated interactor of the proliferation marker Ki-67 at centromere-proximal sites.

    Evidence Yeast two-hybrid screen plus in vitro phosphorylation with mitotic HeLa extracts and immunofluorescence

    PMID:10878014

    Open questions at the time
    • Functional significance of Ki-67–KIF15 interaction for spindle assembly unresolved
    • Kinase responsible for mitotic phosphorylation not identified
  2. 2003 Medium

    Localization studies across multiple cell types revealed that KIF15 associates with bundled microtubule arrays in mitotic spindles, neurons, and actin structures, suggesting a general role in crosslinking cytoskeletal filaments.

    Evidence Immunofluorescence and cell fractionation in fibroblasts, mitotic cells, and cultured neurons/rodent brain sections

    PMID:14618103

    Open questions at the time
    • Direct crosslinking activity not yet demonstrated biochemically
    • Actin association mechanism unknown
  3. 2009 High

    Functional epistasis experiments established that KIF15 cooperates with Eg5 to promote centrosome separation and bipolar spindle assembly, with TPX2 as a key co-factor for KIF15's spindle-localizing activity.

    Evidence RNAi knockdown, ectopic overexpression, live-cell imaging, co-immunoprecipitation, epistasis with Eg5 inhibition in human cells

    PMID:19818618

    Open questions at the time
    • Whether KIF15 crosslinks MTs directly or only via TPX2 was unresolved
    • Motor properties of full-length KIF15 unknown
  4. 2013 High

    Solving the KIF15 motor domain crystal structure revealed a unique ADP-bound yet neck-linker-docked conformation, distinguishing its mechanochemistry from Eg5.

    Evidence X-ray crystallography with biochemical kinetics and MT co-sedimentation

    PMID:24419385

    Open questions at the time
    • Structure of full-length tetramer not resolved
    • Structural basis of autoinhibition unknown
  5. 2014 High

    Reconstitution of full-length KIF15 revealed it is a processive homotetramer capable of crosslinking MTs independently of TPX2, and that TPX2 actually inhibits stepping — overturning the model that TPX2 was required for crosslinking; simultaneously, a two-step autoinhibition/activation mechanism was defined whereby binding two MTs via the C-terminal nonmotor site relieves autoinhibition and targets KIF15 to K-fiber bundles.

    Evidence Single-molecule TIRF, optical trapping, in vitro MT crosslinking assays, domain deletion/mutation analysis, live-cell imaging

    PMID:24668168 PMID:25264249

    Open questions at the time
    • How autoinhibition is structurally implemented at atomic resolution unknown
    • Relative contributions of TPX2-dependent and -independent targeting in vivo unresolved
  6. 2016 High

    The C-terminal domain of TPX2 was shown to regulate KIF15 localization in cells and suppress motor walking in vitro, and dynamic microtubule growth was found to contribute to KIF15 motility at the spindle equator.

    Evidence In vitro MT gliding with TPX2 truncations, live-cell fluorescence, FRAP, paclitaxel treatment

    PMID:27852894

    Open questions at the time
    • Molecular interface between TPX2 C-terminus and KIF15 not mapped
    • Whether MT dynamics drive KIF15 or vice versa not fully disentangled
  7. 2017 High

    Force measurements established that the KIF15 C-terminal tail binds the MT E-hook with rupture force exceeding the motor stall force, enabling selective sliding of antiparallel but not parallel MTs — providing the biophysical basis for outward spindle force generation.

    Evidence Single-molecule optical trapping, fluorescence-based MT gliding, stochastic simulation

    PMID:28918951

    Open questions at the time
    • How the tail domain's affinity is regulated in vivo (e.g., by phosphorylation) unknown
  8. 2018 High

    The KIF15 mechanochemical cycle was defined at single-molecule resolution, and the first chemical inhibitor (KIF15-IN-1) was characterized; dual inhibition of KIF15 and Eg5 synergistically killed cancer cells, establishing KIF15 as a pharmacological target and validating the functional redundancy model.

    Evidence Single-molecule optical trapping, MT gliding assay, cancer cell viability assays

    PMID:29703754

    Open questions at the time
    • In vivo pharmacokinetics and selectivity of KIF15-IN-1 not evaluated
  9. 2018 Medium

    In vivo knockout of kif15 in zebrafish accelerated axonal outgrowth and regeneration, confirming that KIF15 restrains microtubule sliding and axon elongation in neurons.

    Evidence CRISPR/Cas9 knockout in zebrafish, live imaging of neuron development, laser-axotomy regeneration assay

    PMID:30411440

    Open questions at the time
    • Whether KIF15 acts as a brake via crosslinking or via cargo transport in axons not distinguished
    • Mammalian neuronal KO phenotype not yet characterized at this point
  10. 2019 High

    Kinesin-binding protein (KBP) was shown to directly inhibit KIF15 by blocking MT binding, acting as a cellular buffer against excess KIF15 activity and preventing chromosome segregation errors.

    Evidence MT gliding filament assay, MT co-pelleting, live-cell imaging, overexpression/knockdown

    PMID:30709852

    Open questions at the time
    • Structural basis of KBP–KIF15 interaction not resolved
    • How KBP and TPX2 coordinate KIF15 regulation unknown
  11. 2020 High

    Discovery that KIF15 stabilizes AR and AR-V7 by recruiting deubiquitinase USP14 established a non-canonical, motor-independent scaffolding function for KIF15 in protein homeostasis and oncogenic signaling.

    Evidence Co-immunoprecipitation, ubiquitination assay, KIF15 inhibitor/siRNA knockdown, xenograft models

    PMID:33277366

    Open questions at the time
    • Whether motor activity is required for DUB recruitment unknown
    • Generality of DUB-recruitment mechanism to other clients not yet tested
  12. 2021 High

    Multiple studies extended KIF15's protein-stabilizing role: it stabilizes DEK via USP15, prevents EGFR degradation via Cdc42, and crosslinks K-fibers to maintain their mechanical integrity — consolidating a dual role as both a structural crosslinker and a signaling scaffold.

    Evidence Laser ablation of K-fibers with pharmacological perturbation; Co-IP and ubiquitination assays for DEK/USP15 and EGFR/Cdc42; xenograft models

    PMID:34280614 PMID:34668719 PMID:34804913

    Open questions at the time
    • Whether DUB recruitment and MT crosslinking are structurally separable functions unknown
    • Direct binding surfaces for USP15 and Cdc42 on KIF15 not mapped
  13. 2022 Medium

    KIF15 was found to recruit HDAC6, NAT10, and SIRT2 to regulate tubulin acetylation and K-fiber stability in mouse oocyte meiosis, revealing a role in epigenetic modification of tubulin beyond simple crosslinking; separately, KIF15 was shown to interact with PI3K-C2α to promote integrin β1/FAK signaling via RAB11A in pancreatic cancer cells.

    Evidence Co-IP plus mass spectrometry in oocytes, morpholino/siRNA knockdown, SAC marker analysis; kinesin siRNA screen plus Co-IP plus PTM assays in pancreatic cancer cells

    PMID:35835966 PMID:36280663

    Open questions at the time
    • Whether tubulin acetylation regulation is conserved in somatic mitosis unknown
    • PI3K-C2α interaction awaits independent confirmation
  14. 2023 High

    KIF15's protein-stabilizing repertoire was further expanded: it recruits USP10 to deubiquitinate PGK1 (promoting glycolysis) and inhibits MDM2-mediated NRAS ubiquitination (activating Rac signaling), each via distinct domain interactions.

    Evidence MS-identified interactions confirmed by Co-IP, ubiquitination assays, domain truncation, metabolic flux measurements, xenograft models

    PMID:36807568 PMID:37970344

    Open questions at the time
    • Whether KIF15-DUB interactions are competitive or concurrent unknown
    • Structural basis of coil2 domain involvement in USP10 binding not resolved
  15. 2024 Medium

    PRC1-mediated antiparallel MT bundling was shown to enhance KIF15-driven spindle bipolarity, providing the upstream geometric prerequisite for KIF15 activation; separately, KIF15 was found to sequester STAT3 in the cytoplasm, linking it to autophagy regulation.

    Evidence Genetic epistasis with PRC1/TPX2 knockdown/overexpression in Eg5-inhibitor-resistant cells; Co-IP of KIF15-STAT3, autophagy flux assays, in vivo tumor model

    PMID:38598297 PMID:39504712

    Open questions at the time
    • Direct physical interaction between PRC1 and KIF15 not demonstrated
    • STAT3 sequestration mechanism (motor-dependent or not) unresolved
  16. 2025 High

    Neuronal functions of KIF15 were defined: it transports PSD95 to dendritic spines to maintain excitatory synapses, and it interacts with Annexin A2 to restrict TRPA1 channel surface expression in sensory neurons — KIF15-KO mice exhibit mood disorder and cold hypersensitivity phenotypes.

    Evidence Endogenous and exogenous Co-IP, CRISPR/Cas9 Kif15−/− mice, electrophysiology, behavioral assays, membrane fractionation, zebrafish rescue

    PMID:39914618 PMID:40892874

    Open questions at the time
    • Whether PSD95 is a direct cargo transported by KIF15 motor activity or stabilized by scaffolding unknown
    • Mechanism by which Annexin A2 mediates TRPA1 retention not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of KIF15 autoinhibition and its relief by two-MT engagement, whether the motor and protein-stabilization functions are structurally separable, and how KIF15 is directed to its diverse non-mitotic roles in neurons, oocytes, and cancer signaling.
  • No full-length KIF15 structure available
  • Separation-of-function mutants distinguishing motor vs. scaffolding roles not generated
  • Regulation of KIF15 by post-translational modifications (phosphorylation, acetylation) incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0003774 cytoskeletal motor activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0140657 ATP-dependent activity 3
Localization
GO:0005856 cytoskeleton 5 GO:0005694 chromosome 2 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-112316 Neuronal System 2
Partners
HDAC6KBPMDM2PRC1PSD95TPX2USP10USP14
Complex memberships
KIF15 homotetramer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 KIF15 (Kif15/Hklp2) cooperates with Eg5 to promote bipolar spindle assembly and centrosome separation; this activity requires both the KIF15 motor domain and its interaction with the microtubule-associated protein TPX2, consistent with a Kif15-TPX2 complex crosslinking and sliding antiparallel microtubules apart. RNAi knockdown, ectopic overexpression, live-cell imaging, co-immunoprecipitation; epistasis with Eg5 inhibition Current biology : CB High 19818618
2000 KIF15 (Hklp2) was identified as a binding partner of the Ki-67 antigen (pKi-67); the interaction is mediated by the forkhead-associated (FHA) domain of Ki-67 and residues 1017–1237 of Hklp2, which are phosphorylated by mitotic but not interphase cell extracts; the complex localizes to the periphery of mitotic chromosomes near centromeres. Yeast two-hybrid screening, in vitro phosphorylation assay with mitotic HeLa extracts, immunofluorescence The Journal of biological chemistry Medium 10878014
2014 Full-length human KIF15 is a plus-end-directed processive homotetramer capable of stepping against loads up to 3.5 pN; it is the first kinesin shown to effectively switch microtubule tracks at intersections; KIF15 tetramers can crosslink microtubules independently of TPX2; instead, TPX2 inhibits KIF15 stepping when microtubule-bound. In vitro reconstitution of full-length hKIF15 and hTPX2, single-molecule TIRF microscopy, optical trapping, microtubule crosslinking assays eLife High 24668168
2014 KIF15 accumulates selectively on kinetochore fiber (K-fiber) MT bundles via two intrinsic biochemical properties: (1) autoinhibition by its C-terminal domain, and (2) a nonmotor MT-binding site enabling crosslinking; two-MT binding relieves autoinhibition and drives KIF15 accumulation and motility on MT bundles but not single MTs, establishing an intrinsic two-step targeting mechanism that does not require TPX2 for loading. In vitro MT-binding and sliding assays, single-molecule TIRF, deletion/mutation analysis of KIF15 domains, live-cell imaging Current biology : CB High 25264249
2013 Crystal structure of the KIF15 motor domain was solved; the domain contains ADP in the catalytic site but adopts an 'ATP-like' configuration with the neck linker docked to the catalytic core, revealing structural differences from Eg5 that suggest a distinct mode of microtubule crosslinking and sliding. X-ray crystallography, biochemical kinetics, microtubule co-sedimentation assays Acta crystallographica. Section D, Biological crystallography High 24419385
2017 KIF15 dimers slide antiparallel microtubules apart with gradual force buildup while parallel MT bundles remain stationary; the nonmotor C-terminal tail domain binds the MT E-hook with a rupture force exceeding the motor stall force, enabling productive force generation; a stochastic simulation confirmed the tail domain's role in load storage within the KIF15-MT system. Single-molecule optical trapping, in vitro fluorescence-based MT gliding assay, stochastic simulation Current biology : CB High 28918951
2016 The C-terminal domain of TPX2 contributes to KIF15 localization to spindle MTs in cells and suppresses KIF15 motor walking in vitro; Kif15-dependent bipolar spindle formation in vivo requires the C-terminal domain of TPX2; GFP-Kif15 puncta move toward the spindle equator at a rate equivalent to MT growth, and paclitaxel suppression of MT growth inhibits Kif15 motility, demonstrating that dynamic microtubules contribute to Kif15 behavior. In vitro MT gliding assay with TPX2 C-terminal truncations, live-cell fluorescence imaging, FRAP, paclitaxel treatment Molecular biology of the cell High 27852894
2011 In Eg5-inhibited cells, KIF15 (Hklp2) can replace Eg5 in spindle pole separation through a mechanism involving formation of acentrosomal poles enabled by altered microtubule dynamics (TOGp depletion or low-dose nocodazole); resulting bipolar spindles are functional in chromosome segregation. Live-cell imaging, RNAi depletion of TOGp combined with Eg5 inhibitor treatment, siRNA knockdown of Hklp2 Cell cycle (Georgetown, Tex.) Medium 22024925
2003 In mitotic cells, Kif15 localizes to spindle poles and microtubules during prometaphase to early anaphase and relocates to the actin-based cleavage furrow during cytokinesis; in interphase fibroblasts it localizes to actin bundles; in neurons it associates specifically with bundled microtubule arrays (dendrites, stalled growth cones); migratory neurons show pronounced Kif15 enrichment, suggesting Kif15 limits independent microtubule movements within these arrays. Immunofluorescence, cell fractionation, analysis in cultured neurons and developing rodent brain sections Journal of neurocytology Medium 14618103
2018 Single-molecule optical trapping defined the KIF15 mechanochemical cycle; KIF15-IN-1 is a potent inhibitor of KIF15 motility; MT gliding powered by KIF15 and Eg5 ceases only when both motors are inhibited simultaneously; pairing KIF15-IN-1 with Eg5 inhibitors synergistically reduces cancer cell growth. Single-molecule optical trapping, MT gliding assay, cancer cell viability assay Proceedings of the National Academy of Sciences of the United States of America High 29703754
2019 Kinesin-binding protein (KBP) directly inhibits KIF15 motor activity by preventing microtubule binding, as shown by gliding filament and MT co-pelleting assays; KBP overexpression alters mitotic localization of KIF15, decreases spindle length, and causes lagging chromosomes in anaphase; KBP acts as a protein buffer protecting cells from excessive KIF15 activity. MT gliding filament assay, MT co-pelleting assay, immunofluorescence, live-cell imaging, overexpression/knockdown The Journal of cell biology High 30709852
2017 KBP (kinesin-binding protein) is a specific mitotic interaction partner of Kif15 and promotes Kif15 localization to the spindle equator; both Kif15 and KBP are required for alignment of all chromosomes to the metaphase plate and for assembly of stable kinetochore fibers of correct length. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, live-cell imaging PloS one Medium 28445502
2014 KIF15 was identified as a novel regulator of α2β1 integrin endocytic trafficking; KIF15 mediates plasma membrane localization of the alternative clathrin adaptor Dab2, thereby impinging on pathways regulating α2 integrin internalization. Quantitative fluorescence-microscopy-based RNAi screen (386 genes), siRNA validation, imaging of integrin internalization and Dab2 localization Journal of cell science Medium 24659801
2021 Pharmacological inhibition of KIF15-microtubule binding (but not locking KIF15 in a rigor state) reduces the mechanical integrity of K-fibers, demonstrating that KIF15 acts as a microtubule crosslinker to fortify and repair K-fiber bundles and prevent chromosome segregation errors. Laser ablation of K-fibers, pharmacological inhibition with KIF15 inhibitors, quantitative imaging of MT splaying Molecular biology of the cell High 34668719
2022 In mouse oocyte meiosis, KIF15 localizes with microtubules and is responsible for recruiting HDAC6, NAT10, and SIRT2 to maintain acetylated tubulin levels; disruption of KIF15 reduces K-fiber stability, causes loss of kinetochore-MT attachment, activates the spindle assembly checkpoint (Bub3 and BubR1 not released), and leads to chromosome misalignment and high aneuploidy rates. Morpholino/siRNA knockdown, KIF15 inhibitor treatment, co-immunoprecipitation, mass spectrometry, immunofluorescence, spindle assembly checkpoint marker analysis Cellular and molecular life sciences : CMLS High 35835966
2020 KIF15 directly binds the N-terminus of AR and AR-V7, prevents their proteasomal degradation by increasing association of deubiquitinase USP14 with AR/AR-V7, and thereby enhances AR signaling; in a reciprocal feedback, transcriptionally active AR stimulates KIF15 expression. Co-immunoprecipitation, ubiquitination assay, Western blot, KIF15 inhibitor/siRNA knockdown, xenograft models Cancer research High 33277366
2023 KIF15 promotes glycolytic capacity in pancreatic cancer by stabilizing the glycolytic enzyme PGK1; it does so by recruiting deubiquitinase USP10 and enhancing the USP10-PGK1 interaction, thereby reducing PGK1 ubiquitination; this interaction is mediated through the coil2 domain of KIF15. Mass spectrometry, co-immunoprecipitation, ubiquitination assay, domain deletion/truncation analysis, ECAR/OCR measurements, Western blot Cell death & disease High 36807568
2022 In pancreatic cancer cells, KIF15 interacts with PI3K-C2α to promote integrin β1/FAK signaling and focal adhesion disassembly in a RAB11A-dependent and FAK-Y397-dependent manner; SIRT1-mediated acetylation of KIF15 is required for KIF15 phosphorylation (the key activation event for its motor function); the C-terminal tail of KIF15 is required for PI3K-C2α interaction and RAB11A activation. kinesin siRNA library screen for integrin β1 recycling, co-immunoprecipitation, domain truncation analysis, phosphorylation/acetylation assays, FAK signaling readouts Cell death & disease Medium 36280663
2021 KIF15 interacts with and stabilizes the DEK proto-oncogene protein in leiomyosarcoma cells by recruiting USP15, which deubiquitylates DEK; KIF15 knockdown increases DEK polyubiquitylation and facilitates its degradation; USP15 overexpression restores DEK stability in a KIF15-dependent manner. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, Western blot for protein stability Biochemical and biophysical research communications Medium 34280614
2018 In zebrafish, CRISPR/Cas9-mediated kif15 knockout accelerates axonal outgrowth and regeneration velocity after laser-induced axon injury, reduces axonal branching, confirming that Kif15 limits microtubule sliding in axons and restrains axon elongation in vivo. CRISPR/Cas9 knockout in zebrafish, live imaging of motor and sensory neuron development, laser-axotomy regeneration assay Traffic (Copenhagen, Denmark) Medium 30411440
2024 PRC1-mediated antiparallel microtubule bundling enhances KIF15-driven spindle assembly: PRC1 loss reduces spindle bipolarity in KIF15-dependent (Eg5-inhibitor-resistant) cells, PRC1 overexpression increases spindle formation efficiency and promotes Eg5-inhibitor resistance; these effects are not reproduced by TPX2, indicating specificity for antiparallel MT bundling in enabling KIF15 activity. Sibling cell lines with endogenous Eg5-inhibitor resistance, siRNA knockdown of PRC1/TPX2, overexpression, quantitative imaging of spindle bipolarity Molecular biology of the cell Medium 38598297
2021 KIF15 in Sertoli cells associates with microtubules (enriched at apical ectoplasmic specializations) and its RNAi knockdown (~70% reduction) impairs blood-testis barrier function by disrupting organization of MT, actin, vimentin, and septin cytoskeletons, demonstrating that KIF15 coordinates multiple cytoskeletal systems to support spermatid transport. RNAi knockdown in primary Sertoli cells, immunofluorescence, tight junction barrier integrity assay Endocrinology Medium 33453102
2024 KIF15 interacts with STAT3 and sequesters it in the cytoplasm; KIF15 knockdown reduces STAT3's inhibitory effect on ATG7, thereby upregulating autophagy in radiation-resistant nasopharyngeal carcinoma cells and increasing radiosensitivity; METTL3-mediated m6A methylation of KIF15 mRNA underlies its elevated expression in NPC. Co-immunoprecipitation (KIF15-STAT3), STAT3 overexpression rescue, autophagy flux assays, m6A methylation analysis, in vivo tumor model Translational oncology Medium 39504712
2025 In dorsal root ganglion sensory neurons, KIF15 physically interacts with Annexin A2; KIF15 knockout increases membrane localization of the TRPA1 channel, leading to cold hypersensitivity; in an oxaliplatin-induced neuropathy model, KIF15 expression is reduced coinciding with increased TRPA1 membrane accumulation, suggesting KIF15 normally limits TRPA1 surface expression via Annexin A2. Co-immunoprecipitation (KIF15-Annexin A2 in DRG neurons), Kif15-KO mice, behavioral cold sensitivity assays, membrane fractionation of TRPA1 Neuropharmacology Medium 39914618
2025 KIF15 interacts with PSD95 (confirmed by both endogenous and exogenous Co-IP); KIF15 deficiency causes PSD95 to redistribute from the cell membrane to the perinuclear region in neurons, reduces dendritic spine density, decreases excitatory postsynaptic scaffolding (PSD95, NMDA receptors, mEPSC frequency), and upregulates inhibitory scaffold Gephyrin/GABRB1, contributing to mood disorder phenotypes in mice. Co-immunoprecipitation (endogenous and exogenous), CRISPR/Cas9 Kif15-/- mice, electrophysiology (mEPSC), immunofluorescence, behavioral assays, zebrafish rescue with Kif15 overexpression PLoS genetics High 40892874
2014 Aurora A kinase inhibitors overcome KIF15-dependent resistance to the KIF11 (Eg5) inhibitor SB743921; in a KIF15-dependent resistant cell model, Aurora A inhibition combined with KIF11 inhibition promotes monoastral spindle formation and mitotic catastrophe synergistically, indicating parallel pathways of centrosome regulation by Aurora A and KIF11 that KIF15 can partially substitute. Infrared-based cell viability assay, isobologram analysis, live-cell imaging, RNAi-based KIF15-dependent resistance model Molecular oncology Medium 24950801
2023 KIF15 knockdown in colorectal cancer cells reduces NRAS protein stability by increasing its ubiquitination; KIF15 interacts with the E3 ubiquitin ligase MDM2 and reduces MDM2-mediated ubiquitination of NRAS, thereby stabilizing NRAS and activating Rac signaling to promote proliferation and migration. Co-immunoprecipitation, ubiquitination assay, Western blot, siRNA knockdown, xenograft model American journal of cancer research Medium 37970344
2024 In porcine oocytes, KIF15 modulates HDAC6 to regulate tubulin acetylation and microtubule stability; KIF15 deficiency reduces acetylated tubulin, destabilizes spindle microtubules (evidenced by cold depolymerization), causes abnormal spindle morphology and chromosome misalignment, and blocks polar body extrusion. KIF15 morpholino/siRNA knockdown, cold-induced microtubule depolymerization assay, immunofluorescence, immunoprecipitation Theriogenology Medium 38838614
2021 KIF15 interacts with EGFR and prevents EGFR protein degradation in a Cdc42-dependent manner, thereby enhancing EGFR-MAPK and PI3K/AKT signaling in castration-resistant prostate cancer; KIF15 expression is positively correlated with EGFR protein levels in CRPC tumors. Co-immunoprecipitation, Western blot, EGFR degradation assay, Cdc42 perturbation, xenograft model Frontiers in oncology Medium 34804913
2023 METTL3 mediates m6A methylation of KIF15 mRNA, stabilizing KIF15 transcript via reduced mRNA decay; VIRMA promotes KIF15 expression in triple-negative breast cancer through m6A-dependent stabilization of KIF15 mRNA. RNA immunoprecipitation (RIP-qPCR), m6A methylation assay, lentiviral overexpression/knockdown, mRNA stability assay Discovery medicine / Translational oncology Medium 37811616 39504712
2023 In the context of cardiac hypertrophy, FoxO6 transcriptionally activates KIF15 expression; KIF15 upregulation promotes TGF-β1 secretion from cardiomyocytes, which drives fibroblast proliferation and differentiation, thereby contributing to pathological cardiac remodeling. FoxO6 knockout and overexpression mouse models, Ang-II cardiac hypertrophy model, KIF15 inhibition rescue, conditioned medium transfer to fibroblasts, in vitro cardiomyocyte/fibroblast co-culture MedComm Medium 37799807

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Kif15 cooperates with eg5 to promote bipolar spindle assembly. Current biology : CB 226 19818618
2017 KIF15 promotes pancreatic cancer proliferation via the MEK-ERK signalling pathway. British journal of cancer 79 28595260
2020 KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer. Cancer research 76 33277366
2000 The forkhead-associated domain of Ki-67 antigen interacts with the novel kinesin-like protein Hklp2. The Journal of biological chemistry 57 10878014
2014 The Kinesin-12 Kif15 is a processive track-switching tetramer. eLife 54 24668168
2018 KIF15 nanomechanics and kinesin inhibitors, with implications for cancer chemotherapeutics. Proceedings of the National Academy of Sciences of the United States of America 49 29703754
2003 Expression of the mitotic kinesin Kif15 in postmitotic neurons: implications for neuronal migration and development. Journal of neurocytology 48 14618103
2022 Rare and Common Variants in KIF15 Contribute to Genetic Risk of Idiopathic Pulmonary Fibrosis. American journal of respiratory and critical care medicine 47 35417304
2014 Kinesin-12 Kif15 targets kinetochore fibers through an intrinsic two-step mechanism. Current biology : CB 47 25264249
2020 B7-H3 regulates KIF15-activated ERK1/2 pathway and contributes to radioresistance in colorectal cancer. Cell death & disease 44 33011740
2017 Collective Force Regulation in Anti-parallel Microtubule Gliding by Dimeric Kif15 Kinesin Motors. Current biology : CB 43 28918951
2022 Kinesin KIF15 regulates tubulin acetylation and spindle assembly checkpoint in mouse oocyte meiosis. Cellular and molecular life sciences : CMLS 41 35835966
2014 Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance. Molecular oncology 35 24950801
2011 Modulated microtubule dynamics enable Hklp2/Kif15 to assemble bipolar spindles. Cell cycle (Georgetown, Tex.) 31 22024925
2013 The crystal structure and biochemical characterization of Kif15: a bifunctional molecular motor involved in bipolar spindle formation and neuronal development. Acta crystallographica. Section D, Biological crystallography 27 24419385
2016 Regulation of Kif15 localization and motility by the C-terminus of TPX2 and microtubule dynamics. Molecular biology of the cell 26 27852894
2014 An RNAi screen identifies KIF15 as a novel regulator of the endocytic trafficking of integrin. Journal of cell science 26 24659801
2019 KIF15 promotes bladder cancer proliferation via the MEK-ERK signaling pathway. Cancer management and research 25 30881113
2023 KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer. Cell death & disease 24 36807568
2020 KIF15 contributes to cell proliferation and migration in breast cancer. Human cell 24 32578050
2019 Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15. The Journal of cell biology 23 30709852
2020 ZNF367-induced transcriptional activation of KIF15 accelerates the progression of breast cancer. International journal of biological sciences 22 32549756
2018 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated kif15 mutations accelerate axonal outgrowth during neuronal development and regeneration in zebrafish. Traffic (Copenhagen, Denmark) 21 30411440
2017 Role of Kif15 and its novel mitotic partner KBP in K-fiber dynamics and chromosome alignment. PloS one 21 28445502
2021 KIF15 supports spermatogenesis via its effects on Sertoli cell microtubule, actin, vimentin, and septin cytoskeletons. Endocrinology 20 33453102
2020 GSG2 (Haspin) promotes development and progression of bladder cancer through targeting KIF15 (Kinase-12). Aging 19 32439830
2018 Dual inhibition of Kif15 by oxindole and quinazolinedione chemical probes. Bioorganic & medicinal chemistry letters 18 30528696
2024 Polystyrene nanoplastics accelerate atherosclerosis: Unraveling the impact on smooth muscle cells through KIF15-mediated migration. Ecotoxicology and environmental safety 16 39232293
2019 KIF15 plays a role in promoting the tumorigenicity of melanoma. Experimental eye research 16 30797758
2020 KIF15 Promotes Proliferation and Growth of Hepatocellular Carcinoma. Analytical cellular pathology (Amsterdam) 14 32318326
2020 KIF15 promotes the evolution of gastric cancer cells through inhibition of reactive oxygen species-mediated apoptosis. Journal of cellular physiology 14 32342525
2020 KIF11 and KIF15 mitotic kinesins are potential therapeutic vulnerabilities for malignant peripheral nerve sheath tumors. Neuro-oncology advances 14 32642733
2017 Dihydropyrazole and dihydropyrrole structures based design of Kif15 inhibitors as novel therapeutic agents for cancer. Computational biology and chemistry 14 28355588
2022 Dynamic regulation of KIF15 phosphorylation and acetylation promotes focal adhesions disassembly in pancreatic cancer. Cell death & disease 12 36280663
2021 Kinesin 12 (KIF15) contributes to the development and tumorigenicity of prostate cancer. Biochemical and biophysical research communications 12 34474246
2021 K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15. Molecular biology of the cell 12 34668719
2021 KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway. Frontiers in oncology 12 34804913
2023 Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer. Current cancer drug targets 11 35713129
2023 VIRMA Facilitates Triple-Negative Breast Cancer Progression via Increasing m6A-Dependent KIF15 Expression. Discovery medicine 11 37811616
2021 KIF15 knockdown suppresses gallbladder cancer development. European journal of cell biology 11 34781077
2023 KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial-mesenchymal transition and stemness through Wnt/β-catenin signaling. Environmental toxicology 10 37186152
2022 PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer. Cancer biology & therapy 10 36137220
2021 KIF15 is involved in development and progression of Burkitt lymphoma. Cancer cell international 9 33985517
2017 Loss-of-Function Mutations in KIF15 Underlying a Braddock-Carey Genocopy. Human mutation 9 28150392
2024 METTL3 methylated KIF15 promotes nasopharyngeal carcinoma progression and radiation resistance by blocking ATG7-mediated autophagy through the activation of STAT3 pathway. Translational oncology 8 39504712
2021 KIF15 upregulation promotes leiomyosarcoma cell growth via promoting USP15-mediated DEK deubiquitylation. Biochemical and biophysical research communications 8 34280614
2024 KIF15 promotes human glioblastoma progression under the synergistic transactivation of REST and P300. International journal of biological sciences 7 39430242
2023 Anti-aging Effects of Alu Antisense RNA on Human Fibroblast Senescence Through the MEK-ERK Pathway Mediated by KIF15. Current medical science 7 36808398
2023 Forkhead box O6 (FoxO6) promotes cardiac pathological remodeling and dysfunction by activating Kif15-TGF-β1 under aggravated afterload. MedComm 7 37799807
2023 Knockdown of KIF15 suppresses proliferation of prostate cancer cells and induces apoptosis through PI3K/Akt signaling pathway. Cell death discovery 6 37658042
2021 Downregulation of KIF15 inhibits the tumorigenesis of non-small-cell lung cancer via inactivating Raf/MEK/ERK signaling. Histology and histopathology 6 34908156
2019 Benserazide Perturbs Kif15-kinesin Binding Protein Interaction with Prolonged Metaphase and Defects in Chromosomal Congression: A Study Based on in silico Modeling and Cell Culture. Molecular informatics 6 31347789
2024 KIF15 promotes the development and progression of chordoma via activating PI3K-AKT signalling pathway. Heliyon 4 38681556
2024 Insufficient KIF15 during porcine oocyte ageing induces HDAC6-based microtubule instability. Theriogenology 4 38838614
2023 Deficiency of Kif15 gene inhibits tumor growth due to host CD8+T lymphocytes increase. Biochemical and biophysical research communications 4 36934586
2021 Knockdown of KIF15 promotes cell apoptosis by activating crosstalk of multiple pathways in ovarian cancer: bioinformatic and experimental analysis. International journal of clinical and experimental pathology 4 33564360
2025 Atractylenolide I ameliorated the growth and enzalutamide resistance of castration-resistant prostate cancer by targeting KIF15. Chinese medicine 3 40087774
2024 Antiparallel microtubule bundling supports KIF15-driven mitotic spindle assembly. Molecular biology of the cell 3 38598297
2023 Kif15 deficiency contributes to depression-like behavior in mice. Metabolic brain disease 3 37256467
2023 KIF15 knockdown inhibits colorectal cancer proliferation and migration through affecting the ubiquitination modification of NRAS. American journal of cancer research 3 37970344
2025 Deficiency of KIF15 contributes to oxaliplatin-induced cold hypersensitivity by limiting annexin A2 and enhancing TRPA1 localization in DRG neuronal membrane. Neuropharmacology 2 39914618
2024 Kif15 regulates Coro1a+ cell migration and phagocytosis in zebrafish after spinal cord injury. International immunopharmacology 2 39709909
2026 Tumor Microenvironment Characterization Identifies KIF15 as an Immunosuppressive Driver in Breast Cancer. Human mutation 1 41584727
2026 The YY1-KIF15-PRDX1 axis promotes gastric cancer progression by inducing mitochondrial ROS imbalance. Oncogene 0 41912772
2025 The multifaceted role of KIF15 in cancer progression and therapy. Investigational new drugs 0 40817978
2025 Deficiency of Kif15 impairing synaptic development leads to mood disorder in mice. PLoS genetics 0 40892874