Affinage

KIF15

Kinesin-like protein KIF15 · UniProt Q9NS87

Length
1388 aa
Mass
160.2 kDa
Annotated
2026-06-10
68 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF15 (Hklp2/Kinesin-12) is a plus-end-directed processive homotetrameric microtubule motor that drives bipolar mitotic spindle assembly in cooperation with Eg5/KIF11, becoming essential when Eg5 is partially inhibited and able to reconstitute bipolarity in the complete absence of Eg5 activity (PMID:19818618). Single-molecule reconstitution established KIF15 as a processive motor that steps against loads up to 3.5 pN and uniquely switches microtubule tracks at intersections; its tetramers crosslink microtubules and slide antiparallel filaments apart through a non-motor tail domain that binds the tubulin E-hook with a rupture force exceeding the motor stall force, while parallel bundles remain stationary (PMID:24668168, PMID:28918951). KIF15 is self-repressed by its C-terminus and activated by simultaneous binding to two microtubules, which targets it to kinetochore-fiber bundles where it acts principally as a crosslinker to fortify and repair K-fibers rather than through motor activity (PMID:25264249, PMID:34668719). Its activity is tuned by associated factors: TPX2 inhibits stepping when KIF15 is microtubule-bound yet contributes to spindle localization (PMID:24668168, PMID:27852894), kinesin-binding protein (KBP) directly blocks microtubule binding to regulate chromosome alignment and K-fiber length (PMID:28445502, PMID:30709852), and PRC1-mediated antiparallel bundling supports KIF15-driven assembly in Eg5-inhibitor-resistant cells (PMID:38598297). KIF15 upregulation mediates resistance to Eg5 inhibitors, a vulnerability reversible by Aurora A inhibition or direct KIF15 inhibitors (PMID:24950801, PMID:29703754). Beyond mitosis, KIF15 restrains axonal outgrowth and regeneration (PMID:30411440), directs PSD95 and TRPA1 channel localization in neurons (PMID:40892874, PMID:39914618), and in numerous cancers stabilizes client proteins (AR, EGFR, NRAS, DEK, PGK1, PRDX1) by recruiting deubiquitinases or modulating E3 ligase activity, thereby activating MEK-ERK, PI3K-AKT and related growth pathways (PMID:28595260, PMID:33277366, PMID:34804913, PMID:36807568, PMID:37970344, PMID:34280614, PMID:41912772).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2000 Medium

    Established the first molecular partner of KIF15/Hklp2, linking it to mitotic chromosome periphery via a mitosis-specific phosphorylated interaction domain.

    Evidence Yeast two-hybrid, in vitro phosphorylation with cell extracts, and immunofluorescence in HeLa cells

    PMID:10878014

    Open questions at the time
    • Functional consequence of the Ki-67 interaction unresolved
    • Identity of the mitotic kinase not determined
  2. 2003 Medium

    Mapped KIF15 subcellular distribution across mitotic, interphase and neuronal contexts, hinting at roles in microtubule bundling beyond mitosis.

    Evidence Immunofluorescence and localization across multiple cell types including neurons

    PMID:14618103

    Open questions at the time
    • Mechanistic basis for actin vs microtubule association unclear
    • Neuronal function not functionally tested here
  3. 2009 High

    Defined KIF15's central role as an Eg5-cooperating motor that drives bipolar spindle assembly and can substitute for Eg5 when overexpressed.

    Evidence RNAi, Eg5 inhibitors, overexpression rescue, live imaging and epistasis in cells

    PMID:19818618

    Open questions at the time
    • Whether TPX2 is strictly required for crosslinking debated by later in vitro work
    • Direct biochemical demonstration of antiparallel sliding not yet shown
  4. 2011 Medium

    Showed KIF15-driven bipolarization in Eg5-inhibited cells proceeds via altered microtubule dynamics and acentrosomal pole formation.

    Evidence Live imaging, siRNA, and pharmacological inhibition in cells

    PMID:22024925

    Open questions at the time
    • Molecular determinants linking MT dynamics to KIF15 activity unresolved
  5. 2013 High

    Provided the structural and kinetic basis distinguishing KIF15's motor mechanism from Eg5.

    Evidence X-ray crystallography of the motor domain plus kinetic and co-sedimentation assays

    PMID:24419385

    Open questions at the time
    • No full-length or tail-domain structure
    • Mechanistic link between structure and crosslinking not defined
  6. 2014 High

    Reconstitution of full-length KIF15 defined it as a processive, load-bearing tetramer that crosslinks microtubules independently of TPX2 and switches tracks at intersections, reframing the KIF15-TPX2 relationship.

    Evidence In vitro reconstitution with purified hKif15/hTpx2, single-molecule optical trapping and TIRF

    PMID:24668168

    Open questions at the time
    • In vivo relevance of track-switching not established
    • How tetramerization is regulated unclear
  7. 2014 High

    Revealed the autoregulatory two-step activation: C-terminal self-repression relieved by two-microtubule binding drives K-fiber targeting without TPX2 loading.

    Evidence In vitro MT-binding/motility assays, truncations, TIRF and co-pelleting

    PMID:25264249

    Open questions at the time
    • Structural mechanism of C-terminal autoinhibition not solved
    • In vivo trigger for two-MT engagement unclear
  8. 2014 Medium

    Identified KIF15 upregulation as a mechanism of Eg5-inhibitor resistance overridable by Aurora A inhibition, establishing therapeutic relevance.

    Evidence Drug-resistance cell model, live imaging, synergy analysis and siRNA

    PMID:24950801

    Open questions at the time
    • Mechanism connecting Aurora A to KIF15 dependence not defined
  9. 2014 Medium

    Extended KIF15 function beyond mitosis to membrane trafficking by controlling Dab2-dependent integrin internalization.

    Evidence Quantitative RNAi screen with siRNA validation and integrin trafficking assays

    PMID:24659801

    Open questions at the time
    • Direct KIF15-Dab2 interaction not demonstrated
    • Cargo specificity unresolved
  10. 2017 High

    Demonstrated KIF15 generates antiparallel sliding force through its non-motor tail domain binding the tubulin E-hook, clarifying the biophysical basis of crosslinking.

    Evidence Single-molecule optical tweezers, gliding/trapping assays and stochastic simulation

    PMID:28918951

    Open questions at the time
    • Tail-E-hook interaction not structurally resolved
    • Regulation of parallel vs antiparallel selectivity unclear
  11. 2017 Medium

    Identified KBP as a mitotic KIF15 partner required for chromosome alignment and stable K-fiber assembly.

    Evidence Co-IP, immunofluorescence, siRNA and live imaging

    PMID:28445502

    Open questions at the time
    • Direct vs indirect interaction not distinguished in this study
  12. 2019 High

    Showed KBP directly inhibits KIF15 (and KIF18A) motor activity by blocking microtubule binding, defining a negative regulatory mechanism for spindle motors.

    Evidence Gliding filament and co-pelleting assays plus overexpression/knockdown live imaging

    PMID:30709852

    Open questions at the time
    • Structural basis of KBP-motor inhibition not resolved
  13. 2016 Medium

    Refined the TPX2 contribution: its C-terminal domain suppresses KIF15 walking in vitro yet supports spindle localization and dynamic-MT-coupled motility in cells.

    Evidence In vitro motility, TIRF, live imaging, TPX2 truncations and paclitaxel treatment

    PMID:27852894

    Open questions at the time
    • Reconciliation of inhibitory vs localization roles incomplete
  14. 2018 High

    Provided selective KIF15 chemical inhibitors and validated combination with Eg5 inhibition as an anticancer strategy.

    Evidence Single-molecule trapping, MT-gliding, viability and drug-combination assays (KIF15-IN-1); ATPase/motility screen (GW108X)

    PMID:29703754 PMID:30528696

    Open questions at the time
    • In vivo efficacy and selectivity of inhibitors not established here
  15. 2018 Medium

    Established a neuronal role: KIF15 restrains axonal outgrowth, branching and regenerative velocity in vivo.

    Evidence CRISPR/Cas9 knockout in zebrafish with live imaging and laser axotomy

    PMID:30411440

    Open questions at the time
    • Molecular cargo or microtubule substrate in neurons not identified
  16. 2021 Medium

    Demonstrated KIF15 fortifies K-fibers mechanically via its crosslinking (MT-binding) function rather than motor activity.

    Evidence Laser ablation with rigor vs MT-binding inhibitors and live imaging

    PMID:34668719

    Open questions at the time
    • Quantitative contribution relative to other K-fiber crosslinkers unclear
  17. 2021 Medium

    Extended KIF15 spindle function to meiosis (oocytes) and to Sertoli-cell cytoskeletal organization and blood-testis barrier integrity.

    Evidence RNAi knockdown with cytoskeletal immunofluorescence and barrier assays in Sertoli cells

    PMID:33453102

    Open questions at the time
    • Direct molecular targets in Sertoli cytoskeleton unresolved
  18. 2024 Medium

    Defined how K-fiber/spindle stability is maintained via KIF15-dependent control of tubulin acetylation in oocyte meiosis.

    Evidence siRNA/morpholino knockdown, Co-IP, mass spectrometry, cold-depolymerization and SAC marker analysis in mouse and porcine oocytes

    PMID:35835966 PMID:38838614

    Open questions at the time
    • Whether KIF15 directly regulates HDAC6/NAT10/SIRT2 enzymatic activity unresolved
    • Generalizability to mitotic spindle unclear
  19. 2024 Medium

    Showed PRC1-mediated antiparallel bundling specifically supports KIF15-driven assembly in Eg5-inhibitor-resistant cells, distinguishing it from non-selective TPX2 bundling.

    Evidence siRNA, overexpression and drug-resistance assays with TPX2 comparison controls

    PMID:38598297

    Open questions at the time
    • Direct PRC1-KIF15 physical relationship not established
  20. 2026 Medium

    Mapped KIF15-dependent transport and localization functions in neurons (PSD95, TRPA1, CX3CL1) linking it to synaptic scaffolding, cold sensation and neuroimmune signaling.

    Evidence CRISPR/Cas9 KO mice, Co-IP, membrane fractionation, electrophysiology, snRNA-seq and injury/behavior models

    PMID:39914618 PMID:40892874 PMID:42055325

    Open questions at the time
    • Whether KIF15 directly motors these cargoes vs acts indirectly not resolved
    • Microtubule-track dependence of neuronal cargo delivery untested
  21. 2023 Medium

    Established a recurrent oncogenic paradigm whereby KIF15 stabilizes client proteins by recruiting deubiquitinases or modulating E3 ligases to activate growth and metabolic pathways.

    Evidence Co-IP, ubiquitination/protein-stability assays, domain mapping and xenografts across AR, EGFR, NRAS, DEK, PGK1, PRDX1 in multiple cancers

    PMID:28595260 PMID:33277366 PMID:34280614 PMID:34804913 PMID:36807568 PMID:37970344 PMID:41912772

    Open questions at the time
    • How a microtubule motor scaffolds DUB-substrate complexes mechanistically unclear
    • Whether these functions require motor/MT-binding activity untested
  22. 2022 Medium

    Linked KIF15 activation to post-translational regulation, with SIRT1-mediated acetylation required for its phosphorylation and motor activation, coupling it to integrin/FAK signaling and cell migration.

    Evidence siRNA kinesin screen, Co-IP, acetylation/phosphorylation analysis, integrin recycling and RAB11A epistasis with in vivo migration model

    PMID:36280663

    Open questions at the time
    • Acetylation and phosphorylation sites not mapped
    • Direct enzyme-KIF15 contacts not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single autoinhibited microtubule motor is repurposed across mitotic crosslinking, neuronal cargo localization, and DUB-mediated protein stabilization in cancer—and whether the non-mitotic functions depend on its motor/MT-binding activity—remains unresolved.
  • No unifying structural model of full-length autoinhibition and activation
  • Whether cancer scaffolding functions require microtubule binding untested
  • Direct cargo motoring vs indirect localization effects in neurons undistinguished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 4 GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0140657 ATP-dependent activity 2
Localization
GO:0005856 cytoskeleton 4 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-5653656 Vesicle-mediated transport 2
Partners
KBPMDM2PRDX1STAT3TPX2USP10USP14USP15

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 KIF15/Hklp2 interacts with the forkhead-associated (FHA) domain of Ki-67 antigen (pKi-67); the interaction domain of Hklp2 was mapped to residues 1017-1237, which is phosphorylated by mitotic but not interphase HeLa cell extracts. The interaction is strongest in mitotic extract, and immunofluorescence shows co-localization at the periphery of mitotic chromosomes near centromeres. Yeast two-hybrid screening, in vitro phosphorylation assay with mitotic/interphase cell extracts, immunofluorescence The Journal of biological chemistry Medium 10878014
2003 In mitotic cells, Kif15 localizes to spindle poles and microtubules during prometaphase to early anaphase, then relocates to the actin-based cleavage furrow during cytokinesis. In interphase fibroblasts, Kif15 localizes to actin bundles but not microtubules. In cultured neurons, Kif15 localizes specifically to bundled microtubules and is enriched in stalled growth cones and dendrites. Migratory neurons show pronounced Kif15 enrichment, suggesting a role in limiting independent microtubule movements. Immunofluorescence microscopy, subcellular fractionation/localization in multiple cell types Journal of neurocytology Medium 14618103
2009 Kif15/Hklp2 cooperates with Eg5 to promote bipolar spindle assembly. While dispensable when Eg5 is fully active, Kif15 becomes essential when Eg5 is partially inhibited. Ectopic overexpression of Kif15 can fully reconstitute bipolar spindle assembly in the complete absence of Eg5 activity. This activity depends on Kif15's interaction with the microtubule-associated protein TPX2, and requires both its motor domain and its TPX2-binding capability, suggesting the Kif15-TPX2 complex crosslinks and slides antiparallel microtubules to drive centrosome separation. RNAi knockdown, Eg5 inhibitor (monastrol/STLC), ectopic overexpression, live-cell imaging, epistasis analysis Current biology : CB High 19818618
2011 Hklp2/Kif15 drives bipolar spindle assembly in Eg5-inhibited cells through a mechanism involving altered microtubule dynamics. Depletion of TOGp or low-dose nocodazole enables Hklp2/Kif15-dependent bipolarization through formation of acentrosomal poles, a mechanism reminiscent of meiosis. Once bipolar spindles form via Kif15, they no longer require altered microtubule dynamics to maintain bipolarity. Live cell imaging, siRNA depletion, pharmacological inhibition (Eg5 inhibitors, nocodazole) Cell cycle (Georgetown, Tex.) Medium 22024925
2013 Crystal structure of the Kif15 motor domain was solved; the motor domain contains ADP in the catalytic site but is captured in an 'ATP-like' configuration with the neck linker docked to the catalytic core. Biochemical and kinetic characterization revealed differences in microtubule interaction mode between Kif15 and Eg5, indicating profound differences in their mechanism of action consistent with distinct microtubule cross-linking and sliding. X-ray crystallography, biochemical/kinetic characterization, microtubule co-sedimentation assay Acta crystallographica. Section D, Biological crystallography High 24419385
2014 Full-length hKif15 is a plus-end-directed processive homotetramer that steps against loads up to 3.5 pN. hKif15 is the first kinesin shown to switch microtubule tracks at intersections, enabling navigation through microtubule networks. hKif15 tetramers crosslink microtubules independently of hTpx2; instead, hTpx2 inhibits hKif15 stepping when microtubule-bound. In vitro reconstitution of full-length hKif15 and hTpx2, single-molecule optical trapping, TIRF microscopy, motility assays eLife High 24668168
2014 Kif15 accumulates specifically on kinetochore fiber (K-fiber) microtubule bundles via an intrinsic two-step mechanism: (1) Kif15 is self-repressed by its C-terminus, and (2) a non-motor MT-binding site enables dimeric Kif15 to crosslink and slide MTs, with two-MT binding activating Kif15 and driving its accumulation and motility on MT bundles but not individual MTs. This demonstrates that Kif15 K-fiber targeting does not require TPX2 loading as previously proposed. In vitro MT-binding and motility assays, deletion/truncation analysis, TIRF microscopy, MT co-pelleting Current biology : CB High 25264249
2014 KIF15-dependent resistance to Eg5/KIF11 inhibitor SB743921 can be overcome by Aurora A kinase inhibitors, which synergistically promote monoastral spindle formation and mitotic catastrophe. A KIF15-dependent resistance cell model was developed, demonstrating that KIF15 upregulation mediates Eg5-inhibitor resistance and that Aurora A inhibition overrides this resistance. Drug resistance cell model, live-cell imaging, isobologram synergy analysis, siRNA knockdown Molecular oncology Medium 24950801
2014 KIF15 functions as a significant inhibitor of endocytic trafficking of α2 integrin. 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, integrin trafficking assays Journal of cell science Medium 24659801
2016 The C-terminal domain of TPX2 contributes to localization of Kif15 to spindle microtubules in cells and suppresses motor walking in vitro. Kif15-dependent bipolar spindle formation in vivo requires the C-terminal domain of TPX2. GFP-Kif15 fluorescent puncta move toward the spindle equator at a rate equivalent to microtubule growth; reduction of microtubule growth with paclitaxel suppresses GFP-Kif15 motility, demonstrating that dynamic microtubules contribute to Kif15 behavior. In vitro motility assays, live-cell imaging, TIRF microscopy, TPX2 truncation/domain analysis, paclitaxel treatment Molecular biology of the cell Medium 27852894
2017 Kif15 dimers generate forces to slide antiparallel microtubules apart via a mechanism dependent on the non-motor microtubule-binding tail domain, which interacts with the microtubule E-hook with a rupture force higher than the motor stall force, enabling productive force generation. Parallel microtubule bundles remain stationary with only a small antagonizing force. Stochastic simulations confirm the essential role of the tail domain for load storage. Single-molecule optical tweezers, in vitro MT gliding and optical trapping fluorescence assay, stochastic simulation Current biology : CB High 28918951
2017 KBP (kinesin-binding protein) is identified as a specific interaction partner of Kif15 in mitosis. KBP promotes localization of Kif15 to the spindle equator near chromosomes. Both Kif15 and KBP are required for chromosome alignment to the metaphase plate and assembly of stable kinetochore fibers of correct length. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, live-cell imaging PloS one Medium 28445502
2017 KIF15 promotes pancreatic cancer cell proliferation via the MEK-ERK signaling pathway; KIF15 upregulation increases cyclin D1, CDK2, and phospho-RB levels, promotes G1/S transition, and elevates p-MEK and p-ERK levels. MEK-ERK inhibitor PD98059 blocks KIF15-mediated proliferation in vivo and in vitro. siRNA knockdown, overexpression, western blot, cell cycle analysis, in vivo xenograft, MEK inhibitor treatment British journal of cancer Medium 28595260
2018 KIF15 motility differs significantly from Eg5. KIF15-IN-1 is a potent inhibitor of KIF15 motility. MT gliding powered by KIF15 and Eg5 only ceases when both motors are inhibited. Pairing KIF15-IN-1 with Eg5 inhibitors synergistically reduces cancer cell growth, supporting a combination drug strategy. Single-molecule optical trapping, MT-gliding assay, cancer cell viability assay, drug combination analysis Proceedings of the National Academy of Sciences of the United States of America High 29703754
2018 CRISPR/Cas9-mediated kif15 knockout in zebrafish accelerates axonal outgrowth and increases axon length in primary motor neurons and Rohon-Beard sensory neurons, while reducing axon branching. After laser-induced axon injury in R-B sensory neurons, kif15 knockout significantly increases regenerative velocity. CRISPR/Cas9 gene knockout in zebrafish, live imaging of transgenic/labeled neurons, laser axotomy and regeneration assay Traffic (Copenhagen, Denmark) Medium 30411440
2018 GW108X (an oxindole) inhibits Kif15 in vitro with a mechanism of action distinct from the commercially available Kif15-IN-1 inhibitor, providing a novel chemical probe for Kif15 inhibition. In vitro kinesin ATPase/motility assay, small molecule screen of kinase inhibitor library Bioorganic & medicinal chemistry letters Medium 30528696
2019 Kinesin-binding protein (KBP) directly inhibits KIF18A and KIF15 motor activity by preventing microtubule binding, as demonstrated by gliding filament and microtubule co-pelleting assays. KBP overexpression disrupts chromosome movement/alignment and decreases spindle length (phenotypes matching KIF18A and KIF15 deficiency). KBP depletion causes lagging chromosomes in anaphase, recapitulated by KIF15 and KIF18A overexpression. Gliding filament assay, MT co-pelleting assay, overexpression, siRNA knockdown, live-cell imaging The Journal of cell biology High 30709852
2020 KIF15 directly binds the N-terminus of AR and AR-V7, and prevents AR/AR-V7 protein degradation by increasing the protein association of ubiquitin-specific protease 14 (USP14) with AR/AR-V7, thereby stabilizing AR protein and promoting enzalutamide resistance. In turn, transcriptionally active AR stimulates KIF15 expression, forming a reciprocal feedback loop. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, AR protein stability assay, xenograft model Cancer research Medium 33277366
2020 B7-H3 regulates KIF15 expression (via NF-κB-independent pathway); KIF15 in turn activates ERK1/2 signaling to confer radioresistance in colorectal cancer. siRNA-mediated KIF15 silencing or KIF15 inhibitor (SB743921) abolishes B7-H3-mediated radioresistance both in vitro and in vivo. RNA sequencing, siRNA knockdown, pharmacological inhibition, clonogenic survival assay, in vivo tumor model Cell death & disease Medium 33011740
2021 KIF15 is essential for spermatid transport in Sertoli cells; KIF15 knockdown by RNAi impedes blood-testis barrier function through disruption of microtubule, actin, vimentin, and septin cytoskeletal organization in Sertoli cells. RNAi knockdown in primary Sertoli cells, immunofluorescence for cytoskeletal proteins, tight junction barrier function assay Endocrinology Medium 33453102
2021 Pharmacological inhibition of Kif15-microtubule binding (not its motor activity) reduces the mechanical integrity of k-fibers (kinetochore fiber bundles), demonstrating that Kif15 acts as a microtubule cross-linker to fortify and repair k-fibers rather than primarily through its motor activity. Laser ablation of k-fibers, pharmacological inhibition with motor-null (rigor) vs. MT-binding inhibitors, live-cell imaging Molecular biology of the cell Medium 34668719
2021 KIF15 binds to EGFR and prevents EGFR protein degradation in a Cdc42-dependent manner in castration-resistant prostate cancer, thereby enhancing EGFR signaling including MAPK and PI3K/AKT pathways. Increased KIF15 expression is positively correlated with EGFR protein level in CRPC tumors. Co-immunoprecipitation, protein stability assay, Cdc42 inhibition, western blot, knockdown/overexpression Frontiers in oncology Medium 34804913
2022 KIF15 depletion in mouse oocyte meiosis does not affect spindle morphology but causes chromosome misalignment due to reduced K-fiber stability, which leads to loss of kinetochore-microtubule attachment and activates the spindle assembly checkpoint (SAC), evidenced by failed release of Bub3 and BubR1. Mass spectrometry and Co-IP showed KIF15 recruits HDAC6, NAT10, and SIRT2 to maintain tubulin acetylation levels, which affects microtubule stability. siRNA knockdown, mass spectrometry, Co-immunoprecipitation, immunofluorescence, SAC marker analysis Cellular and molecular life sciences : CMLS Medium 35835966
2022 SIRT1-mediated acetylation of KIF15 is essential for KIF15 phosphorylation (the key activation event for motor protein function). KIF15 recruits PI3K-C2α via its C-terminal tail domain to promote integrin β1/FAK signaling and focal adhesion disassembly in a RAB11A-dependent manner, promoting pancreatic cancer cell migration. siRNA kinesin library screen, Co-IP, integrin recycling assay, SIRT1 inhibition, acetylation/phosphorylation analysis, in vivo migration model Cell death & disease Medium 36280663
2023 KIF15 promotes PGK1 protein stability and glycolytic capacity in pancreatic cancer by recruiting USP10 deubiquitinase to PGK1, thereby reducing PGK1 ubiquitination. The KIF15 coil2 domain mediates binding to both PGK1 and USP10. Co-IP and ubiquitination assays confirm the KIF15/USP10/PGK1 axis. Mass spectrometry, Co-immunoprecipitation, ubiquitination assay, KIF15 truncation/domain analysis, ECAR/OCR metabolic measurements, siRNA knockdown Cell death & disease Medium 36807568
2023 KIF15 interacts with STAT3, retaining it in the cytoplasm. KIF15 knockdown decreases STAT3's inhibitory effect on ATG7, thereby upregulating autophagy, and METTL3-mediated m6A methylation increases KIF15 mRNA stability to promote radioresistance in NPC. Overexpression of STAT3 reverses the inhibitory effects of KIF15 knockdown on autophagy. Co-immunoprecipitation, m6A RNA immunoprecipitation, STAT3 localization assay, autophagy flux analysis, overexpression/knockdown epistasis Translational oncology Medium 39504712
2023 KIF15 interacts with PSD95 protein (demonstrated by endogenous and exogenous Co-IP). In Kif15-/- mice, PSD95 is distributed around neuronal nuclei rather than at cell membranes, demonstrating KIF15 is required for proper PSD95 transport/localization. Kif15 deficiency reduces excitatory postsynaptic scaffolding (PSD95, NMDAR) and dendritic spine density while increasing inhibitory scaffolding (Gephyrin, GABRB1), contributing to bipolar disorder-like behavior. CRISPR/Cas9 knockout mice, endogenous and exogenous Co-IP, immunofluorescence, electrophysiology (mEPSC), behavioral assays, zebrafish rescue experiments PLoS genetics Medium 40892874
2023 KIF15 knockdown reduces NRAS protein stability by increasing ubiquitination of NRAS. KIF15 interacts with the E3 ubiquitin ligase MDM2 (by Co-IP), and this interaction reduces ubiquitination modification of NRAS, stabilizing NRAS protein and activating the Rac signaling pathway to promote colorectal cancer proliferation and migration. Co-immunoprecipitation, ubiquitination assay, western blot, siRNA knockdown, xenograft model American journal of cancer research Medium 37970344
2024 KIF15 modulates HDAC6 to affect tubulin acetylation and maintain microtubule stability in porcine oocytes; KIF15 localization depends on microtubule dynamics. KIF15 deficiency causes spindle morphology defects, chromosome misalignment due to microtubule instability (shown by cold treatment depolymerization), and blocks polar body extrusion during aging. Morpholino/siRNA knockdown, immunofluorescence, cold-induced MT depolymerization assay, tubulin acetylation analysis Theriogenology Medium 38838614
2024 PRC1-mediated antiparallel microtubule bundling supports KIF15-driven mitotic spindle assembly in Eg5-inhibitor-resistant cells (KIRCs). Loss of PRC1 in KIRCs decreases spindle bipolarity; PRC1 overexpression increases spindle formation efficiency and protects naïve cells against Eg5 inhibitors; PRC1 overexpression promotes establishment of Eg5-inhibitor resistance. These effects are not fully reproduced by TPX2 (a non-orientation-selective MT bundler). siRNA knockdown, overexpression, spindle bipolarity assays, drug resistance assays, comparison with TPX2 overexpression controls Molecular biology of the cell Medium 38598297
2024 KIF15 deficiency in dorsal root ganglion neurons leads to reduced Annexin A2 function at the cell membrane and increased TRPA1 channel membrane localization, contributing to cold hypersensitivity. KIF15 physically interacts with Annexin A2 in peripheral sensory neurons. In oxaliplatin-induced peripheral neuropathy, KIF15 expression is markedly reduced, coinciding with increased TRPA1 membrane localization. KIF15 knockout mice, Co-immunoprecipitation, immunofluorescence/membrane fractionation, behavioral cold sensitivity assay, oxaliplatin neuropathy model Neuropharmacology Medium 39914618
2024 KIF15 inhibitor treatment increases migration and phagocytosis of macrophages in vitro, associated with increased activation of Cdc42 and RhoA. In zebrafish kif15 morphants with spinal cord injury, Coro1a+ immune cells show increased recruitment then rapid decline, with enhanced phagocytic capacity. Zebrafish morpholino knockdown, Kif15 pharmacological inhibition, phagocytosis assay, Cdc42/RhoA activation assay, live imaging International immunopharmacology Medium 39709909
2021 KIF15 upregulation in leiomyosarcoma promotes cell proliferation by preventing DEK protein degradation via increasing USP15-mediated deubiquitylation of DEK. Co-IP confirms mutual interaction between KIF15 and DEK, and between USP15 and both DEK and KIF15. USP15 knockdown decreases DEK stability and cancels KIF15-mediated DEK stabilization. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown, protein stability assay Biochemical and biophysical research communications Medium 34280614
2023 FoxO6 transcription factor directly activates Kif15 expression as a downstream molecule; Kif15 inhibition attenuates the aggravating effect of FoxO6 overexpression on cardiac hypertrophy. KIF15 promotes TGF-β1 release from cardiomyocytes, which induces fibroblast proliferation and differentiation, establishing the FoxO6/Kif15/TGF-β1 axis in cardiac pathological remodeling. FoxO6 knockout/overexpression mice, Ang-II cardiac hypertrophy model, Kif15 inhibition, cardiomyocyte-fibroblast co-culture, TGF-β1 measurement MedComm Medium 37799807
2024 REST transcription factor binds to the KIF15 promoter and transactivates KIF15 expression; REST interacts with the histone acetyltransferase P300 and depends on P300's HAT activity to co-regulate KIF15 expression. Both REST and P300 promote GBM progression via KIF15. Chromatin immunoprecipitation, promoter reporter assay, co-immunoprecipitation (REST-P300 interaction), overexpression/knockdown, P300 HAT inhibitor treatment, xenograft International journal of biological sciences Medium 39430242
2026 KIF15 interacts with peroxiredoxin 1 (PRDX1) to stabilize PRDX1 protein, reducing intracellular hydroperoxides and maintaining mitochondrial function. Depletion of PRDX1 reverses KIF15-mediated oncogenic effects. YY1 transcription factor directly binds the KIF15 promoter to activate KIF15 expression, and YY1 also directly transcriptionally regulates PRDX1. Co-immunoprecipitation, protein stability assay, PRDX1 knockdown rescue, YY1 ChIP, promoter binding assay, ROS measurement, in vivo xenograft Oncogene Medium 41912772
2026 Kif15 facilitates the expression and localization of neuronal CX3CL1 (fractalkine); in Kif15 KO mice, CX3CL1-CX3CR1 signaling between neurons and microglia is downregulated. Kif15 knockout mice show accelerated functional recovery after sciatic nerve injury, associated with a repair-promoting microglial profile and neuroprotective neuronal gene expression changes. CRISPR/Cas9 Kif15 KO mice, single-nucleus RNA sequencing, CX3CL1 localization assay, sciatic nerve injury model The Journal of biological chemistry Medium 42055325

Source papers

Stage 0 corpus · 68 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 80 28595260
2020 KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer. Cancer research 77 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 45 33011740
2022 Kinesin KIF15 regulates tubulin acetylation and spindle assembly checkpoint in mouse oocyte meiosis. Cellular and molecular life sciences : CMLS 43 35835966
2017 Collective Force Regulation in Anti-parallel Microtubule Gliding by Dimeric Kif15 Kinesin Motors. Current biology : CB 43 28918951
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
2014 An RNAi screen identifies KIF15 as a novel regulator of the endocytic trafficking of integrin. Journal of cell science 27 24659801
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
2023 KIF15 is essential for USP10-mediated PGK1 deubiquitination during the glycolysis of pancreatic cancer. Cell death & disease 26 36807568
2016 Regulation of Kif15 localization and motility by the C-terminus of TPX2 and microtubule dynamics. Molecular biology of the cell 26 27852894
2019 KIF15 promotes bladder cancer proliferation via the MEK-ERK signaling pathway. Cancer management and research 25 30881113
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
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) 23 30411440
2020 ZNF367-induced transcriptional activation of KIF15 accelerates the progression of breast cancer. International journal of biological sciences 22 32549756
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 20 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 17 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
2021 KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway. Frontiers in oncology 13 34804913
2023 Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer. Current cancer drug targets 12 35713129
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
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
2024 KIF15 promotes human glioblastoma progression under the synergistic transactivation of REST and P300. International journal of biological sciences 10 39430242
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
2017 Loss-of-Function Mutations in KIF15 Underlying a Braddock-Carey Genocopy. Human mutation 10 28150392
2021 KIF15 is involved in development and progression of Burkitt lymphoma. Cancer cell international 9 33985517
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
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
2023 Deficiency of Kif15 gene inhibits tumor growth due to host CD8+T lymphocytes increase. Biochemical and biophysical research communications 5 36934586
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 Kif15 deficiency contributes to depression-like behavior in mice. Metabolic brain disease 4 37256467
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
2024 Kif15 regulates Coro1a+ cell migration and phagocytosis in zebrafish after spinal cord injury. International immunopharmacology 3 39709909
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
2026 Tumor Microenvironment Characterization Identifies KIF15 as an Immunosuppressive Driver in Breast Cancer. Human mutation 1 41584727
2025 Deficiency of Kif15 impairing synaptic development leads to mood disorder in mice. PLoS genetics 1 40892874
2026 The YY1-KIF15-PRDX1 axis promotes gastric cancer progression by inducing mitochondrial ROS imbalance. Oncogene 0 41912772
2026 Kif15 orchestrates neuronal-microglial communication via CX3CL1 to impede nerve regeneration. The Journal of biological chemistry 0 42055325
2026 KIF15 (Kinesin-12): molecular biology, physiological functions, and roles in disease. Journal of cancer research and clinical oncology 0 42107035
2025 The multifaceted role of KIF15 in cancer progression and therapy. Investigational new drugs 0 40817978

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