{"gene":"KIF14","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2006,"finding":"KIF14 interacts with PRC1 (protein-regulating cytokinesis 1) and targets to the central spindle via this interaction. KIF14 depletion causes citron kinase to fail to localize to the central spindle and midbody. KIF14 and citron kinase localization to the central spindle and midbody is codependent, and they form a complex depending on the activation state of citron kinase.","method":"Co-immunoprecipitation of endogenous proteins, RNAi depletion, immunofluorescence localization","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP of endogenous proteins, RNAi depletion with specific localization phenotype, multiple orthogonal methods in a focused mechanistic study","pmids":["16431929"],"is_preprint":false},{"year":2006,"finding":"RNAi-mediated silencing of KIF14 induces cytokinesis failure, causing endoreduplication and multinucleated cells. KIF14 accumulates at spindle poles, spindle microtubules, and the midbody during mitosis. Partial KIF14 depletion (hypomorphic) causes multiple cell cycle phenotypes and acute apoptosis, while strong depletion causes cytokinesis failure.","method":"RNAi knockdown, time-lapse microscopy, immunofluorescence","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple siRNAs with graded phenotypes, time-lapse imaging, replicated across multiple conditions","pmids":["16648480"],"is_preprint":false},{"year":2012,"finding":"KIF14 associates with the PDZ domain of Radil and negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. Depletion of KIF14 leads to increased cell spreading, altered focal adhesion dynamics, and inhibition of cell migration and invasion.","method":"Co-immunoprecipitation, pulldown assay, RNAi knockdown with cell spreading/migration assays, integrin activation assay","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, functional RNAi phenotypes with multiple readouts, pathway placement via Rap1-Radil signaling axis","pmids":["23209302"],"is_preprint":false},{"year":2014,"finding":"The mouse KIF14 motor domain binds tightly to microtubules and does not display typical nucleotide-dependent changes in microtubule affinity. It has robust ATPase activity but very slow motility. Crystal structure of the ADP-bound motor domain reveals a dramatically opened ATP-binding pocket with central β-sheet twisted ~10° beyond the maximal amount seen in other kinesins (rigor-like state). Cryo-EM fitting shows a distinct binding configuration to microtubules.","method":"Crystal structure (X-ray crystallography), cryo-electron microscopy, in vitro ATPase assay, microtubule co-sedimentation assay, motility assay","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus cryo-EM, in vitro biochemical assays, multiple orthogonal methods in a single focused study","pmids":["24949858"],"is_preprint":false},{"year":2014,"finding":"KIF14 knockdown in hepatocellular carcinoma cells decreases Skp2 and Cks1 levels, leading to accumulation of p27(Kip1) protein by inhibiting its proteasome-dependent degradation. Overexpression of Skp2 in KIF14 knockdown cells attenuates cytokinesis failure, placing KIF14 upstream of the SCF(Skp2) complex in regulating p27(Kip1) ubiquitination.","method":"RNAi knockdown, western blot for SCF complex components, overexpression rescue, cell cycle analysis","journal":"Experimental & molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis rescue experiment with Skp2 overexpression, multiple molecular targets examined, single lab","pmids":["24854087"],"is_preprint":false},{"year":2014,"finding":"KIF14 ectopic expression promotes AKT phosphorylation and activity. Live-cell imaging confirmed an insulin-induced temporal colocalization of KIF14 and AKT at the plasma membrane. KIF14 knockdown correlates with decreased AKT phosphorylation. A small-molecule inhibitor of KIF14 reduces AKT activation.","method":"Live-cell imaging (colocalization), western blot (AKT phosphorylation), RNAi knockdown, overexpression, small-molecule inhibitor treatment","journal":"Neoplasia (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live-cell colocalization and functional assays, multiple experimental approaches, single lab","pmids":["24784001"],"is_preprint":false},{"year":2013,"finding":"KIF14 loss-of-function mutations (autosomal recessive truncating mutations) cause a lethal fetal ciliopathy syndrome in humans with IUGR, microcephaly, renal cystic dysplasia, and brain malformations. Phenotype links KIF14 function in cell division/cytokinesis to primary cilia.","method":"Whole-exome sequencing, genetic segregation analysis in families","journal":"Clinical genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — human genetic evidence, segregation confirmed, replicated across families; no direct cellular mechanism experiment in this paper","pmids":["24128419"],"is_preprint":false},{"year":2017,"finding":"Homozygous loss-of-function mutations in KIF14 cause primary microcephaly (MCPH) in humans. Patient-derived fibroblasts show impaired localization of both KIF14 and CRIK (citron kinase) at the midbody, and exhibit binucleated and apoptotic cells—hallmarks of failed cytokinesis. KIF14-depleted cells recapitulate these cytokinesis defects. Kif14 knockout mice also show primary microcephaly.","method":"Whole-exome sequencing, immunofluorescence of patient fibroblasts, RNAi depletion in cells, Kif14 knockout mouse model","journal":"Annals of neurology","confidence":"High","confidence_rationale":"Tier 2 / Strong — human genetics combined with patient cell functional studies and mouse knockout model, multiple orthogonal methods, replicated across 3 families","pmids":["28892560"],"is_preprint":false},{"year":2013,"finding":"Kif14 splice-site mutation in mice (laggard) causes severe brain malformation, hypomyelination, and reduced expression of myelin-related genes. Kif14 knockout mice phenocopy laggard. Transgenic complementation with wild-type Kif14 cDNA rescues ataxic phenotype. Disrupted cytoarchitecture of cerebellar and cerebral cortices results from apoptotic cell death.","method":"Positional cloning, transgenic complementation, Kif14 knockout mouse generation, gene expression analysis, histology","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — positional cloning, knockout, and transgenic rescue in vivo, multiple orthogonal approaches in one study","pmids":["23308235"],"is_preprint":false},{"year":2020,"finding":"The intrinsically disordered N-terminal domain of KIF14 enables unique functional diversity: (1) enables diffusibility of monomeric KIF14, (2) renders dimeric KIF14 super-processive and enables passage through crowded areas, (3) enables autonomous tracking of growing microtubule tips independent of EB proteins, and (4) is sufficient for crosslinking parallel microtubules and necessary for driving sliding of antiparallel microtubules. The disordered domain interacts diffusibly with the microtubule lattice and shows increased affinity for GTP-bound tubulin.","method":"Single-molecule TIRF microscopy in vitro, domain deletion/truncation analysis, microtubule tip-tracking assays, microtubule sliding assays","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with single-molecule imaging, domain mutagenesis, multiple functional readouts in one study","pmids":["32649913"],"is_preprint":false},{"year":2020,"finding":"KIF14 depletion leads to defects in primary ciliogenesis and basal body biogenesis, impairing efficiency of primary cilium formation and elongation dynamics, and disrupting localization of distal appendage proteins SCLT1 and FBF1 and IFT-B complex components. Deregulated Aurora A activity is identified as a mechanism contributing to cilia and basal body formation defects after KIF14 depletion. Primary cilia in KIF14-depleted cells are also defective in response to Hedgehog pathway activation, independently of Aurora A.","method":"RNAi depletion, immunofluorescence, live-cell imaging, epistasis with Aurora A inhibition, Hedgehog pathway reporter assay","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal experiments (imaging, pathway inhibition epistasis, IFT component localization), mechanistic dissection of two independent pathways in one study","pmids":["32348467"],"is_preprint":false},{"year":2013,"finding":"KIF14 overexpression inhibits anchorage-independent growth in vitro and xenograft tumor growth in vivo in lung adenocarcinoma, and modulates cancer cell migration, invasion, and adhesion to extracellular matrix. Cadherins CDH11 and MCAM were detected as cargo on KIF14; KIF14 overexpression enhances recruitment of CDH11 to the membrane fraction, suggesting KIF14 transports adhesion molecules to the cell membrane.","method":"Co-immunoprecipitation (cargo identification), cell fractionation (membrane fraction), overexpression and knockdown functional assays, xenograft mouse model","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP for cargo identification combined with membrane fractionation and functional validation, single lab","pmids":["23626713"],"is_preprint":false},{"year":2023,"finding":"KIF14 binds the G3BP1/YBX1 complex and facilitates their interaction, causing increased NF-κB promoter activity and activation of the NF-κB pathway in cholangiocarcinoma cells.","method":"Co-immunoprecipitation, NF-κB promoter reporter assay, gain- and loss-of-function studies","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus reporter assay for pathway activity, single lab with multiple assays","pmids":["36922675"],"is_preprint":false},{"year":2024,"finding":"BUB1 phosphorylates KIF14 at serine 1292 (Ser1292). Overexpression of the KIF14-ΔSer1292 mutant (non-phosphorylatable) fails to facilitate aggressiveness of anaplastic thyroid cancer cells compared to wild-type KIF14, demonstrating that BUB1-mediated phosphorylation of KIF14 at Ser1292 is required for the BUB1/KIF14 complex to drive chromosome instability.","method":"Phosphorylation site identification, phospho-mutant overexpression, cell viability and invasion assays, xenograft model","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phospho-mutant functional rescue experiment demonstrating site-specific phosphorylation requirement, single lab","pmids":["38498903"],"is_preprint":false},{"year":2021,"finding":"LETM1 physically binds KIF14 (demonstrated by co-immunoprecipitation). Interference with LETM1 causes downregulation of KIF14 expression and leads to inhibition of proliferation, invasion, migration, and angiogenesis in esophageal squamous cell carcinoma cells.","method":"Co-immunoprecipitation, RNAi knockdown, proliferation/invasion/migration/tubule formation assays","journal":"Bioengineered","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP, single lab, downstream effects may be indirect","pmids":["34605738"],"is_preprint":false},{"year":2025,"finding":"KIF14 binds directly to the focal adhesion protein vinculin and mediates its delivery to the leading edge of migrating colorectal cancer cells. KIF14 overexpression promotes focal adhesion assembly while KIF14 knockdown disrupts it. The transcription factor E2F1 directly binds the KIF14 promoter to drive its transcription, and E2F1 effects on metastasis are mediated through KIF14.","method":"Co-immunoprecipitation (KIF14-vinculin), chromatin immunoprecipitation (E2F1-KIF14 promoter), transcriptomic analysis, overexpression/knockdown functional assays, in vivo metastasis model","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP for binding partner identification plus ChIP for transcriptional regulation, rescue experiments, single lab with multiple orthogonal methods","pmids":["40931756"],"is_preprint":false},{"year":2026,"finding":"MYCBP2 (a ubiquitin E3 ligase) regulates KIF14 protein stability through ubiquitination. KIF14 expression is associated with better overall survival in AML, and KIF14 knockdown partially reverses the effects of MYCBP2 knockdown on cell viability and apoptosis, placing KIF14 downstream of MYCBP2-mediated ubiquitin-proteasome regulation.","method":"Gene Set Enrichment Analysis, siRNA knockdown, flow cytometry, co-immunoprecipitation (implied), in vivo xenograft model","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — ubiquitination mechanism inferred from pathway analysis and partial rescue, direct E3-substrate ubiquitination not biochemically reconstituted in the abstract","pmids":["42036047"],"is_preprint":false},{"year":2025,"finding":"Phosphorylation of citron kinase (CIT-K) at S699 by CDK1/Aurora B reduces its ability to interact with KIF14 at the midbody. This phosphorylation-dependent regulation of the CIT-K/KIF14 interaction controls midbody formation and stability.","method":"Phospho-mutant analysis, co-immunoprecipitation, immunofluorescence, cytokinesis functional assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phospho-mutant Co-IP and functional assays, mechanistic dissection of kinase-regulated interaction, preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.08.25.672096"],"is_preprint":true},{"year":2025,"finding":"KIF14 localizes within primary cilia and drives processive runs along the ciliary axoneme. KIF14 depletion impairs intraflagellar transport (IFT). The motor domain drives processive ciliary motility in cooperation with the C-terminal CC1 domain. C-terminal truncations of KIF14 (including patient mutation Q1380x) cause traffic-jam-like accumulations of ciliary components in the distal cilia, leading to bulged cilia tips.","method":"Live-cell imaging, expansion microscopy, TIRF microscopy (in vitro and in cells), RNAi depletion, domain truncation analysis, patient mutation functional characterization","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro single-molecule TIRF plus live-cell imaging, domain dissection, patient mutation tested; preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.03.20.644298"],"is_preprint":true},{"year":2014,"finding":"Transcriptional regulation of KIF14 overexpression in ovarian cancer involves Sp1 and YY1 transcription factors binding to the KIF14 promoter. ChIP confirmed enrichment of Sp1 and YY1 at the endogenous KIF14 promoter in high-KIF14-expressing ovarian cancer cell lines. siRNA knockdown of Sp1 and YY1 reduced endogenous KIF14 expression. miR-93, miR-144, and miR-382 post-transcriptionally regulate KIF14 mRNA levels.","method":"Promoter deletion analysis, ChIP, siRNA knockdown, miRNA mimic/inhibitor treatment","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP for direct promoter binding plus functional siRNA knockdown, miRNA functional validation, single lab with multiple orthogonal methods","pmids":["24626475"],"is_preprint":false},{"year":2026,"finding":"KIF14 depletion reduces AKT phosphorylation, decreases GPX4 and SLC7A11 expression, increases ACSL4, and sensitizes triple-negative breast cancer cells to ferroptosis. Reciprocal co-immunoprecipitation supports a physical association between endogenous KIF14 and AKT. AKT activator SC79 partially reverses the biochemical and ferroptosis phenotypes caused by KIF14 depletion.","method":"Reciprocal co-immunoprecipitation (KIF14-AKT), RNAi knockdown, western blot, ferroptosis assays (MDA, Fe2+, ferrostatin-1 rescue), AKT activator rescue","journal":"Open life sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP for physical interaction, multiple orthogonal functional assays, AKT rescue experiment, single lab","pmids":["42083583"],"is_preprint":false}],"current_model":"KIF14 is a kinesin-3 family microtubule motor protein that localizes to the central spindle and midbody during cytokinesis by interacting with PRC1, where it recruits citron kinase (CIT-K) to enable successful cell division; its rigor-like, tight microtubule-binding motor domain supports midbody microtubule stabilization, while its intrinsically disordered N-terminal domain enables super-processivity, microtubule tip-tracking, and antiparallel microtubule sliding; beyond cytokinesis, KIF14 regulates primary ciliogenesis and IFT through Aurora A modulation, controls integrin activation by tethering the Radil-Rap1 effector on microtubules, promotes AKT phosphorylation (via physical association with AKT), transports adhesion molecules (CDH11, vinculin) to the cell membrane, and is subject to transcriptional regulation by Sp1/YY1/E2F1 and post-translational regulation including BUB1-mediated phosphorylation at Ser1292 and MYCBP2-mediated ubiquitination."},"narrative":{"mechanistic_narrative":"KIF14 is a microtubule motor that drives the completion of cytokinesis by organizing the central spindle and midbody [PMID:16431929, PMID:16648480]. It targets to the central spindle through interaction with PRC1 and recruits citron kinase (CIT-K/CRIK), with which it localizes codependently to the midbody to enable abscission; loss of KIF14 produces cytokinesis failure, endoreduplication, and multinucleated cells [PMID:16431929, PMID:16648480]. The CIT-K/KIF14 interaction is gated by mitotic kinase phosphorylation of CIT-K, coupling midbody stability to cell-cycle signaling [PMID:bio_10.1101_2025.08.25.672096]. The motor itself is biochemically unusual: its motor domain binds microtubules tightly in a rigor-like state with robust ATPase activity but very slow motility, adopting an exceptionally twisted central β-sheet [PMID:24949858], while an intrinsically disordered N-terminal domain confers super-processivity, autonomous microtubule plus-end tip-tracking, parallel microtubule crosslinking, and antiparallel microtubule sliding [PMID:32649913]. Beyond division, KIF14 functions in primary ciliogenesis and intraflagellar transport, where its depletion disrupts basal body and distal appendage protein localization and deregulates Aurora A activity [PMID:32348467]. KIF14 also acts in cell adhesion and migration, tethering the Radil–Rap1 effector on microtubules to restrain inside-out integrin activation [PMID:23209302] and delivering adhesion cargoes such as vinculin to the leading edge to support focal adhesion assembly [PMID:40931756]. Biallelic loss-of-function mutations in KIF14 cause a lethal fetal ciliopathy and primary microcephaly, with patient cells recapitulating the midbody-localization and cytokinesis defects [PMID:24128419, PMID:28892560]. KIF14 expression is driven transcriptionally by Sp1, YY1, and E2F1 [PMID:24626475, PMID:40931756], and it is widely studied as a proliferation- and migration-promoting factor across cancers.","teleology":[{"year":2006,"claim":"Established how KIF14 acts in cell division by placing it on the central spindle and linking it to the essential cytokinesis kinase citron kinase.","evidence":"Reciprocal endogenous Co-IP, RNAi depletion, and immunofluorescence in cultured cells, plus time-lapse imaging of cytokinesis phenotypes","pmids":["16431929","16648480"],"confidence":"High","gaps":["Did not resolve the structural basis of midbody microtubule engagement","Mechanism by which CIT-K activation state gates complex formation left undefined"]},{"year":2012,"claim":"Extended KIF14 function beyond mitosis by showing it scaffolds the Radil-Rap1 axis on microtubules to control integrin activation and migration.","evidence":"Co-IP and pulldown for Radil PDZ binding plus RNAi with spreading, migration, and integrin activation assays","pmids":["23209302"],"confidence":"High","gaps":["Whether motor activity vs. static tethering drives Radil sequestration not separated","Link to the mitotic role unestablished"]},{"year":2013,"claim":"Defined the in vivo physiological requirement for Kif14 in brain development via loss-of-function mouse and human genetics, connecting cytokinesis to neurodevelopmental disease.","evidence":"Positional cloning, knockout and transgenic rescue in mice; whole-exome sequencing and segregation in human ciliopathy families","pmids":["23308235","24128419"],"confidence":"High","gaps":["Did not dissect which molecular activity (cytokinesis vs. cilia) drives the brain phenotype","Cellular mechanism not assayed in the human genetics report"]},{"year":2014,"claim":"Determined the motor's unusual mechanochemistry, revealing a rigor-like microtubule-binding state with strong ATPase but minimal motility.","evidence":"X-ray crystal structure of the ADP-bound motor domain, cryo-EM fitting, and in vitro ATPase, co-sedimentation, and motility assays (mouse motor domain)","pmids":["24949858"],"confidence":"High","gaps":["Full-length motor behavior not addressed","Functional consequence of the tight-binding state in cells not tested here"]},{"year":2014,"claim":"Implicated KIF14 in cancer signaling networks, placing it upstream of SCF(Skp2)/p27 control of the cell cycle and as a promoter of AKT activation.","evidence":"RNAi, western blot, overexpression rescue for the Skp2/p27 axis; live-cell colocalization, knockdown, and small-molecule inhibition for AKT; ChIP and siRNA for Sp1/YY1 transcriptional control","pmids":["24854087","24784001","24626475"],"confidence":"Medium","gaps":["Whether KIF14 directly or indirectly affects Skp2/p27 not resolved","Mechanism of KIF14-AKT functional coupling not defined biochemically here"]},{"year":2017,"claim":"Confirmed that KIF14 loss causes primary microcephaly through failed cytokinesis, validating the disease mechanism in patient cells and knockout mice.","evidence":"Whole-exome sequencing, immunofluorescence of patient fibroblasts showing impaired KIF14/CRIK midbody localization, RNAi, and Kif14 knockout mice","pmids":["28892560"],"confidence":"High","gaps":["Did not test contribution of ciliary defects to microcephaly","Quantitative threshold of KIF14 function required for division not defined"]},{"year":2020,"claim":"Assigned distinct functional roles to KIF14's domains and discovered a ciliary function, showing the disordered N-terminus enables processivity/tip-tracking/sliding while depletion disrupts ciliogenesis via Aurora A.","evidence":"Single-molecule TIRF reconstitution with domain truncations; RNAi, imaging, Aurora A inhibition epistasis, and Hedgehog reporter assays","pmids":["32649913","32348467"],"confidence":"High","gaps":["How the disordered domain's in vitro activities map onto specific in-cell ciliary/mitotic functions not directly linked","Aurora A-independent Hedgehog defect mechanism unresolved"]},{"year":2025,"claim":"Clarified ciliary mechanism and adhesion-cargo transport, showing KIF14 runs processively along the axoneme driving IFT and delivers vinculin to the leading edge under E2F1 transcriptional control.","evidence":"Live-cell/expansion/TIRF imaging with domain and patient-mutation analysis (preprint); Co-IP for vinculin, ChIP for E2F1, and metastasis models","pmids":["bio_10.1101_2025.03.20.644298","40931756"],"confidence":"Medium","gaps":["Ciliary motility findings remain in preprint, not peer-reviewed","Whether cargo transport and IFT roles share a common motor mechanism not established"]},{"year":2026,"claim":"Extended post-translational regulation and signaling outputs, identifying BUB1 phosphorylation, MYCBP2 ubiquitination, and a KIF14-AKT axis modulating ferroptosis.","evidence":"Phospho-mutant rescue (Ser1292), GSEA with partial knockdown rescue for MYCBP2, and reciprocal Co-IP with AKT-activator rescue in cancer cells","pmids":["38498903","42036047","42083583"],"confidence":"Medium","gaps":["MYCBP2-mediated ubiquitination not biochemically reconstituted","Direct vs. indirect KIF14-AKT coupling unresolved"]},{"year":null,"claim":"How KIF14's rigor-like, slow motor and its super-processive disordered-domain behavior are integrated into a single molecule to perform both midbody stabilization and processive ciliary/cargo transport remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No unified model linking motor mechanochemistry to its distinct cytokinetic, ciliary, and adhesion roles","Structure of full-length KIF14 in cargo-bound states not determined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[3,9,18]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[3]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[3,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,11,15]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3,9]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[10,18]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[5,11,15]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,1,7]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[10,18]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,5,20]},{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[2,15]}],"complexes":["central spindle/midbody","KIF14-citron kinase complex","KIF14-PRC1 complex"],"partners":["PRC1","CIT","RADIL","AKT1","VCL","BUB1","MYCBP2","G3BP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15058","full_name":"Kinesin-like protein KIF14","aliases":[],"length_aa":1648,"mass_kda":186.5,"function":"Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302)","subcellular_location":"Nucleus; Cytoplasm; Cytoplasm, cytoskeleton, spindle; Midbody","url":"https://www.uniprot.org/uniprotkb/Q15058/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF14","classification":"Common Essential","n_dependent_lines":708,"n_total_lines":1208,"dependency_fraction":0.5860927152317881},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"GORASP2","stoichiometry":0.2},{"gene":"TJP2","stoichiometry":0.2},{"gene":"TUBA1B","stoichiometry":0.2},{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KIF14","total_profiled":1310},"omim":[{"mim_id":"617914","title":"MICROCEPHALY 20, PRIMARY, AUTOSOMAL RECESSIVE; MCPH20","url":"https://www.omim.org/entry/617914"},{"mim_id":"616258","title":"MECKEL SYNDROME 12; MKS12","url":"https://www.omim.org/entry/616258"},{"mim_id":"611279","title":"KINESIN FAMILY MEMBER 14; KIF14","url":"https://www.omim.org/entry/611279"},{"mim_id":"251200","title":"MICROCEPHALY 1, PRIMARY, AUTOSOMAL RECESSIVE; MCPH1","url":"https://www.omim.org/entry/251200"},{"mim_id":"249000","title":"MECKEL SYNDROME, TYPE 1; MKS1","url":"https://www.omim.org/entry/249000"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"End piece","reliability":"Supported"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Midbody ring","reliability":"Additional"},{"location":"Calyx","reliability":"Additional"},{"location":"Connecting piece","reliability":"Additional"},{"location":"Mid piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"bone marrow","ntpm":6.2},{"tissue":"lymphoid tissue","ntpm":10.2}],"url":"https://www.proteinatlas.org/search/KIF14"},"hgnc":{"alias_symbol":["KIAA0042"],"prev_symbol":[]},"alphafold":{"accession":"Q15058","domains":[{"cath_id":"3.40.850.10","chopping":"355-610_620-710","consensus_level":"high","plddt":86.657,"start":355,"end":710},{"cath_id":"2.60.200.20","chopping":"797-908","consensus_level":"medium","plddt":82.3387,"start":797,"end":908},{"cath_id":"1.20.1440.210","chopping":"1259-1395","consensus_level":"medium","plddt":83.6571,"start":1259,"end":1395},{"cath_id":"1.20.1410","chopping":"1429-1550_1563-1587","consensus_level":"medium","plddt":78.2639,"start":1429,"end":1587}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15058","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15058-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15058-F1-predicted_aligned_error_v6.png","plddt_mean":65.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIF14","jax_strain_url":"https://www.jax.org/strain/search?query=KIF14"},"sequence":{"accession":"Q15058","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15058.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15058/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15058"}},"corpus_meta":[{"pmid":"16431929","id":"PMC_16431929","title":"KIF14 and citron kinase act together to promote efficient cytokinesis.","date":"2006","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/16431929","citation_count":232,"is_preprint":false},{"pmid":"15897902","id":"PMC_15897902","title":"KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers.","date":"2005","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/15897902","citation_count":148,"is_preprint":false},{"pmid":"16648480","id":"PMC_16648480","title":"RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16648480","citation_count":106,"is_preprint":false},{"pmid":"16570270","id":"PMC_16570270","title":"KIF14 mRNA expression is a predictor of grade and outcome in breast cancer.","date":"2006","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/16570270","citation_count":95,"is_preprint":false},{"pmid":"24784001","id":"PMC_24784001","title":"KIF14 promotes AKT phosphorylation and contributes to chemoresistance in triple-negative breast cancer.","date":"2014","source":"Neoplasia (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/24784001","citation_count":84,"is_preprint":false},{"pmid":"24128419","id":"PMC_24128419","title":"Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype.","date":"2013","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24128419","citation_count":81,"is_preprint":false},{"pmid":"23209302","id":"PMC_23209302","title":"KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression.","date":"2012","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/23209302","citation_count":67,"is_preprint":false},{"pmid":"28892560","id":"PMC_28892560","title":"Mutations of KIF14 cause primary microcephaly by impairing cytokinesis.","date":"2017","source":"Annals of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/28892560","citation_count":65,"is_preprint":false},{"pmid":"31823805","id":"PMC_31823805","title":"Long non-coding RNA PAXIP1-AS1 facilitates cell invasion and angiogenesis of glioma by recruiting transcription factor ETS1 to upregulate KIF14 expression.","date":"2019","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/31823805","citation_count":64,"is_preprint":false},{"pmid":"23479679","id":"PMC_23479679","title":"A targeted RNAi screen of the breast cancer genome identifies KIF14 and TLN1 as genes that modulate docetaxel chemosensitivity in triple-negative breast cancer.","date":"2013","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/23479679","citation_count":62,"is_preprint":false},{"pmid":"29343805","id":"PMC_29343805","title":"Biallelic variants in KIF14 cause intellectual disability with microcephaly.","date":"2018","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/29343805","citation_count":59,"is_preprint":false},{"pmid":"24854087","id":"PMC_24854087","title":"Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27(Kip1) ubiquitination pathway in hepatocellular carcinoma.","date":"2014","source":"Experimental & molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/24854087","citation_count":50,"is_preprint":false},{"pmid":"30226594","id":"PMC_30226594","title":"KIF14 promotes cell proliferation via activation of Akt and is directly targeted by miR-200c in colorectal cancer.","date":"2018","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/30226594","citation_count":46,"is_preprint":false},{"pmid":"23308235","id":"PMC_23308235","title":"Kif14 mutation causes severe brain malformation and hypomyelination.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23308235","citation_count":41,"is_preprint":false},{"pmid":"24949858","id":"PMC_24949858","title":"KIF14 binds tightly to microtubules and adopts a rigor-like conformation.","date":"2014","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/24949858","citation_count":40,"is_preprint":false},{"pmid":"23626713","id":"PMC_23626713","title":"The motor protein KIF14 inhibits tumor growth and cancer metastasis in lung adenocarcinoma.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23626713","citation_count":39,"is_preprint":false},{"pmid":"36922675","id":"PMC_36922675","title":"KIF14 promotes proliferation, lymphatic metastasis and chemoresistance through G3BP1/YBX1 mediated NF-κB pathway in cholangiocarcinoma.","date":"2023","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/36922675","citation_count":38,"is_preprint":false},{"pmid":"26536004","id":"PMC_26536004","title":"Inhibition of KIF14 Suppresses Tumor Cell Growth and Promotes Apoptosis in Human Glioblastoma.","date":"2015","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/26536004","citation_count":35,"is_preprint":false},{"pmid":"17962437","id":"PMC_17962437","title":"High expression of KIF14 in retinoblastoma: association with older age at diagnosis.","date":"2007","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/17962437","citation_count":35,"is_preprint":false},{"pmid":"23414349","id":"PMC_23414349","title":"Suppression of KIF14 expression inhibits hepatocellular carcinoma progression and predicts favorable outcome.","date":"2013","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/23414349","citation_count":35,"is_preprint":false},{"pmid":"24626475","id":"PMC_24626475","title":"Transcriptional and epigenetic regulation of KIF14 overexpression in ovarian cancer.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24626475","citation_count":31,"is_preprint":false},{"pmid":"19190782","id":"PMC_19190782","title":"KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association.","date":"2009","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/19190782","citation_count":27,"is_preprint":false},{"pmid":"28504687","id":"PMC_28504687","title":"The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis.","date":"2017","source":"Laboratory investigation; a journal of technical methods and pathology","url":"https://pubmed.ncbi.nlm.nih.gov/28504687","citation_count":25,"is_preprint":false},{"pmid":"32348467","id":"PMC_32348467","title":"KIF14 controls ciliogenesis via regulation of Aurora A and is important for Hedgehog signaling.","date":"2020","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32348467","citation_count":25,"is_preprint":false},{"pmid":"25106407","id":"PMC_25106407","title":"Sox17 inhibits hepatocellular carcinoma progression by downregulation of KIF14 expression.","date":"2014","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25106407","citation_count":22,"is_preprint":false},{"pmid":"33203790","id":"PMC_33203790","title":"Silencing KIF14 reverses acquired resistance to sorafenib in hepatocellular carcinoma.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/33203790","citation_count":21,"is_preprint":false},{"pmid":"32649913","id":"PMC_32649913","title":"Intrinsically Disordered Domain of Kinesin-3 Kif14 Enables Unique Functional Diversity.","date":"2020","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/32649913","citation_count":20,"is_preprint":false},{"pmid":"33239895","id":"PMC_33239895","title":"Histone Demethylase KDM3A Promotes Cervical Cancer Malignancy Through the ETS1/KIF14/Hedgehog Axis.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33239895","citation_count":16,"is_preprint":false},{"pmid":"35439960","id":"PMC_35439960","title":"KIF14 affects cell cycle arrest and cell viability in cervical cancer by regulating the p27Kip1 pathway.","date":"2022","source":"World journal of surgical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35439960","citation_count":15,"is_preprint":false},{"pmid":"32679794","id":"PMC_32679794","title":"The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer.","date":"2020","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/32679794","citation_count":15,"is_preprint":false},{"pmid":"34605738","id":"PMC_34605738","title":"LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) silence reduces the proliferation, invasion, migration and angiogenesis in esophageal squamous cell carcinoma via KIF14 (kinesin family member 14).","date":"2021","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/34605738","citation_count":14,"is_preprint":false},{"pmid":"36822388","id":"PMC_36822388","title":"KIF14 mediates cabazitaxel-docetaxel cross-resistance in advanced prostate cancer by promoting AKT phosphorylation.","date":"2023","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/36822388","citation_count":13,"is_preprint":false},{"pmid":"36367621","id":"PMC_36367621","title":"MiR-17-3p Facilitates Aggressive Cell Phenotypes in Colon Cancer by Targeting PLCD1 Through Affecting KIF14.","date":"2022","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/36367621","citation_count":13,"is_preprint":false},{"pmid":"32214824","id":"PMC_32214824","title":"MiR-154-5p Suppresses Cell Invasion and Migration Through Inhibiting KIF14 in Nasopharyngeal Carcinoma.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32214824","citation_count":12,"is_preprint":false},{"pmid":"25528264","id":"PMC_25528264","title":"The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells.","date":"2014","source":"Journal of ovarian research","url":"https://pubmed.ncbi.nlm.nih.gov/25528264","citation_count":12,"is_preprint":false},{"pmid":"38498903","id":"PMC_38498903","title":"BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability.","date":"2024","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38498903","citation_count":9,"is_preprint":false},{"pmid":"32757684","id":"PMC_32757684","title":"miR-340 Exerts Suppressive Effect on Retinoblastoma Progression by Targeting KIF14.","date":"2020","source":"Current eye research","url":"https://pubmed.ncbi.nlm.nih.gov/32757684","citation_count":9,"is_preprint":false},{"pmid":"30385851","id":"PMC_30385851","title":"Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30385851","citation_count":8,"is_preprint":false},{"pmid":"38033864","id":"PMC_38033864","title":"Novel circular RNA circ-0002727 regulates miR-144-3p/KIF14 pathway to promote lung adenocarcinoma progression.","date":"2023","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/38033864","citation_count":7,"is_preprint":false},{"pmid":"38590579","id":"PMC_38590579","title":"RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14.","date":"2024","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38590579","citation_count":7,"is_preprint":false},{"pmid":"40374610","id":"PMC_40374610","title":"Identification of tRF-29-79MP9P9NH525 as a biomarker and tumor suppressor of gastric cancer via regulating KIF14/AKT pathway.","date":"2025","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/40374610","citation_count":3,"is_preprint":false},{"pmid":"37091312","id":"PMC_37091312","title":"Replication Timing Aberration of KIF14 and MDM4 /  2 β Alleles and Aneuploidy as Markers of Chromosomal Instability and Poor Treatment Response in Ewing Family Tumor Patients.","date":"2023","source":"Global medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37091312","citation_count":2,"is_preprint":false},{"pmid":"40931756","id":"PMC_40931756","title":"The E2F1‒KIF14 axis drives focal adhesion formation and promotes colorectal cancer metastasis.","date":"2025","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/40931756","citation_count":1,"is_preprint":false},{"pmid":"41511650","id":"PMC_41511650","title":"KIF14 in cancer biology: implications for diagnosis and therapy.","date":"2026","source":"Clinical & experimental metastasis","url":"https://pubmed.ncbi.nlm.nih.gov/41511650","citation_count":1,"is_preprint":false},{"pmid":"40927771","id":"PMC_40927771","title":"RCN1 Binds KIF14 and Promotes the Malignant Growth of Cervical Cancer Through the PI3K-AKT Pathway.","date":"2025","source":"International journal of general medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40927771","citation_count":1,"is_preprint":false},{"pmid":"40717607","id":"PMC_40717607","title":"KIF14 as a Dual Microtubule/F-Actin Binding Protein Contributing to Cytokinesis.","date":"2025","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/40717607","citation_count":0,"is_preprint":false},{"pmid":"42083583","id":"PMC_42083583","title":"KIF14-AKT axis regulates ferroptosis sensitivity in triple-negative breast cancer.","date":"2026","source":"Open life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/42083583","citation_count":0,"is_preprint":false},{"pmid":"42036047","id":"PMC_42036047","title":"Ubiquitin E3 ligase MYCBP2 targets KIF14 and contributes to acute myeloid leukemia progression.","date":"2026","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/42036047","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.03.20.644298","title":"Kinesin-3 KIF14 Regulates Intraflagellar Transport Dynamics in Primary Cilia","date":"2025-03-20","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.20.644298","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.08.25.672096","title":"Coordinated regulation of Citron kinase by CDK1 and Aurora B regulates midbody formation and stability","date":"2025-08-25","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.25.672096","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":27033,"output_tokens":5509,"usd":0.081867,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14009,"output_tokens":3716,"usd":0.081473,"stage2_stop_reason":"end_turn"},"total_usd":0.16334,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"KIF14 interacts with PRC1 (protein-regulating cytokinesis 1) and targets to the central spindle via this interaction. KIF14 depletion causes citron kinase to fail to localize to the central spindle and midbody. KIF14 and citron kinase localization to the central spindle and midbody is codependent, and they form a complex depending on the activation state of citron kinase.\",\n      \"method\": \"Co-immunoprecipitation of endogenous proteins, RNAi depletion, immunofluorescence localization\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP of endogenous proteins, RNAi depletion with specific localization phenotype, multiple orthogonal methods in a focused mechanistic study\",\n      \"pmids\": [\"16431929\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"RNAi-mediated silencing of KIF14 induces cytokinesis failure, causing endoreduplication and multinucleated cells. KIF14 accumulates at spindle poles, spindle microtubules, and the midbody during mitosis. Partial KIF14 depletion (hypomorphic) causes multiple cell cycle phenotypes and acute apoptosis, while strong depletion causes cytokinesis failure.\",\n      \"method\": \"RNAi knockdown, time-lapse microscopy, immunofluorescence\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple siRNAs with graded phenotypes, time-lapse imaging, replicated across multiple conditions\",\n      \"pmids\": [\"16648480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"KIF14 associates with the PDZ domain of Radil and negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. Depletion of KIF14 leads to increased cell spreading, altered focal adhesion dynamics, and inhibition of cell migration and invasion.\",\n      \"method\": \"Co-immunoprecipitation, pulldown assay, RNAi knockdown with cell spreading/migration assays, integrin activation assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, functional RNAi phenotypes with multiple readouts, pathway placement via Rap1-Radil signaling axis\",\n      \"pmids\": [\"23209302\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The mouse KIF14 motor domain binds tightly to microtubules and does not display typical nucleotide-dependent changes in microtubule affinity. It has robust ATPase activity but very slow motility. Crystal structure of the ADP-bound motor domain reveals a dramatically opened ATP-binding pocket with central β-sheet twisted ~10° beyond the maximal amount seen in other kinesins (rigor-like state). Cryo-EM fitting shows a distinct binding configuration to microtubules.\",\n      \"method\": \"Crystal structure (X-ray crystallography), cryo-electron microscopy, in vitro ATPase assay, microtubule co-sedimentation assay, motility assay\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus cryo-EM, in vitro biochemical assays, multiple orthogonal methods in a single focused study\",\n      \"pmids\": [\"24949858\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KIF14 knockdown in hepatocellular carcinoma cells decreases Skp2 and Cks1 levels, leading to accumulation of p27(Kip1) protein by inhibiting its proteasome-dependent degradation. Overexpression of Skp2 in KIF14 knockdown cells attenuates cytokinesis failure, placing KIF14 upstream of the SCF(Skp2) complex in regulating p27(Kip1) ubiquitination.\",\n      \"method\": \"RNAi knockdown, western blot for SCF complex components, overexpression rescue, cell cycle analysis\",\n      \"journal\": \"Experimental & molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis rescue experiment with Skp2 overexpression, multiple molecular targets examined, single lab\",\n      \"pmids\": [\"24854087\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KIF14 ectopic expression promotes AKT phosphorylation and activity. Live-cell imaging confirmed an insulin-induced temporal colocalization of KIF14 and AKT at the plasma membrane. KIF14 knockdown correlates with decreased AKT phosphorylation. A small-molecule inhibitor of KIF14 reduces AKT activation.\",\n      \"method\": \"Live-cell imaging (colocalization), western blot (AKT phosphorylation), RNAi knockdown, overexpression, small-molecule inhibitor treatment\",\n      \"journal\": \"Neoplasia (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live-cell colocalization and functional assays, multiple experimental approaches, single lab\",\n      \"pmids\": [\"24784001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF14 loss-of-function mutations (autosomal recessive truncating mutations) cause a lethal fetal ciliopathy syndrome in humans with IUGR, microcephaly, renal cystic dysplasia, and brain malformations. Phenotype links KIF14 function in cell division/cytokinesis to primary cilia.\",\n      \"method\": \"Whole-exome sequencing, genetic segregation analysis in families\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — human genetic evidence, segregation confirmed, replicated across families; no direct cellular mechanism experiment in this paper\",\n      \"pmids\": [\"24128419\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Homozygous loss-of-function mutations in KIF14 cause primary microcephaly (MCPH) in humans. Patient-derived fibroblasts show impaired localization of both KIF14 and CRIK (citron kinase) at the midbody, and exhibit binucleated and apoptotic cells—hallmarks of failed cytokinesis. KIF14-depleted cells recapitulate these cytokinesis defects. Kif14 knockout mice also show primary microcephaly.\",\n      \"method\": \"Whole-exome sequencing, immunofluorescence of patient fibroblasts, RNAi depletion in cells, Kif14 knockout mouse model\",\n      \"journal\": \"Annals of neurology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — human genetics combined with patient cell functional studies and mouse knockout model, multiple orthogonal methods, replicated across 3 families\",\n      \"pmids\": [\"28892560\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Kif14 splice-site mutation in mice (laggard) causes severe brain malformation, hypomyelination, and reduced expression of myelin-related genes. Kif14 knockout mice phenocopy laggard. Transgenic complementation with wild-type Kif14 cDNA rescues ataxic phenotype. Disrupted cytoarchitecture of cerebellar and cerebral cortices results from apoptotic cell death.\",\n      \"method\": \"Positional cloning, transgenic complementation, Kif14 knockout mouse generation, gene expression analysis, histology\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — positional cloning, knockout, and transgenic rescue in vivo, multiple orthogonal approaches in one study\",\n      \"pmids\": [\"23308235\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The intrinsically disordered N-terminal domain of KIF14 enables unique functional diversity: (1) enables diffusibility of monomeric KIF14, (2) renders dimeric KIF14 super-processive and enables passage through crowded areas, (3) enables autonomous tracking of growing microtubule tips independent of EB proteins, and (4) is sufficient for crosslinking parallel microtubules and necessary for driving sliding of antiparallel microtubules. The disordered domain interacts diffusibly with the microtubule lattice and shows increased affinity for GTP-bound tubulin.\",\n      \"method\": \"Single-molecule TIRF microscopy in vitro, domain deletion/truncation analysis, microtubule tip-tracking assays, microtubule sliding assays\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with single-molecule imaging, domain mutagenesis, multiple functional readouts in one study\",\n      \"pmids\": [\"32649913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF14 depletion leads to defects in primary ciliogenesis and basal body biogenesis, impairing efficiency of primary cilium formation and elongation dynamics, and disrupting localization of distal appendage proteins SCLT1 and FBF1 and IFT-B complex components. Deregulated Aurora A activity is identified as a mechanism contributing to cilia and basal body formation defects after KIF14 depletion. Primary cilia in KIF14-depleted cells are also defective in response to Hedgehog pathway activation, independently of Aurora A.\",\n      \"method\": \"RNAi depletion, immunofluorescence, live-cell imaging, epistasis with Aurora A inhibition, Hedgehog pathway reporter assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal experiments (imaging, pathway inhibition epistasis, IFT component localization), mechanistic dissection of two independent pathways in one study\",\n      \"pmids\": [\"32348467\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF14 overexpression inhibits anchorage-independent growth in vitro and xenograft tumor growth in vivo in lung adenocarcinoma, and modulates cancer cell migration, invasion, and adhesion to extracellular matrix. Cadherins CDH11 and MCAM were detected as cargo on KIF14; KIF14 overexpression enhances recruitment of CDH11 to the membrane fraction, suggesting KIF14 transports adhesion molecules to the cell membrane.\",\n      \"method\": \"Co-immunoprecipitation (cargo identification), cell fractionation (membrane fraction), overexpression and knockdown functional assays, xenograft mouse model\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP for cargo identification combined with membrane fractionation and functional validation, single lab\",\n      \"pmids\": [\"23626713\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KIF14 binds the G3BP1/YBX1 complex and facilitates their interaction, causing increased NF-κB promoter activity and activation of the NF-κB pathway in cholangiocarcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, NF-κB promoter reporter assay, gain- and loss-of-function studies\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus reporter assay for pathway activity, single lab with multiple assays\",\n      \"pmids\": [\"36922675\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BUB1 phosphorylates KIF14 at serine 1292 (Ser1292). Overexpression of the KIF14-ΔSer1292 mutant (non-phosphorylatable) fails to facilitate aggressiveness of anaplastic thyroid cancer cells compared to wild-type KIF14, demonstrating that BUB1-mediated phosphorylation of KIF14 at Ser1292 is required for the BUB1/KIF14 complex to drive chromosome instability.\",\n      \"method\": \"Phosphorylation site identification, phospho-mutant overexpression, cell viability and invasion assays, xenograft model\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phospho-mutant functional rescue experiment demonstrating site-specific phosphorylation requirement, single lab\",\n      \"pmids\": [\"38498903\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"LETM1 physically binds KIF14 (demonstrated by co-immunoprecipitation). Interference with LETM1 causes downregulation of KIF14 expression and leads to inhibition of proliferation, invasion, migration, and angiogenesis in esophageal squamous cell carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown, proliferation/invasion/migration/tubule formation assays\",\n      \"journal\": \"Bioengineered\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP, single lab, downstream effects may be indirect\",\n      \"pmids\": [\"34605738\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"KIF14 binds directly to the focal adhesion protein vinculin and mediates its delivery to the leading edge of migrating colorectal cancer cells. KIF14 overexpression promotes focal adhesion assembly while KIF14 knockdown disrupts it. The transcription factor E2F1 directly binds the KIF14 promoter to drive its transcription, and E2F1 effects on metastasis are mediated through KIF14.\",\n      \"method\": \"Co-immunoprecipitation (KIF14-vinculin), chromatin immunoprecipitation (E2F1-KIF14 promoter), transcriptomic analysis, overexpression/knockdown functional assays, in vivo metastasis model\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP for binding partner identification plus ChIP for transcriptional regulation, rescue experiments, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"40931756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"MYCBP2 (a ubiquitin E3 ligase) regulates KIF14 protein stability through ubiquitination. KIF14 expression is associated with better overall survival in AML, and KIF14 knockdown partially reverses the effects of MYCBP2 knockdown on cell viability and apoptosis, placing KIF14 downstream of MYCBP2-mediated ubiquitin-proteasome regulation.\",\n      \"method\": \"Gene Set Enrichment Analysis, siRNA knockdown, flow cytometry, co-immunoprecipitation (implied), in vivo xenograft model\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ubiquitination mechanism inferred from pathway analysis and partial rescue, direct E3-substrate ubiquitination not biochemically reconstituted in the abstract\",\n      \"pmids\": [\"42036047\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Phosphorylation of citron kinase (CIT-K) at S699 by CDK1/Aurora B reduces its ability to interact with KIF14 at the midbody. This phosphorylation-dependent regulation of the CIT-K/KIF14 interaction controls midbody formation and stability.\",\n      \"method\": \"Phospho-mutant analysis, co-immunoprecipitation, immunofluorescence, cytokinesis functional assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phospho-mutant Co-IP and functional assays, mechanistic dissection of kinase-regulated interaction, preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.08.25.672096\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"KIF14 localizes within primary cilia and drives processive runs along the ciliary axoneme. KIF14 depletion impairs intraflagellar transport (IFT). The motor domain drives processive ciliary motility in cooperation with the C-terminal CC1 domain. C-terminal truncations of KIF14 (including patient mutation Q1380x) cause traffic-jam-like accumulations of ciliary components in the distal cilia, leading to bulged cilia tips.\",\n      \"method\": \"Live-cell imaging, expansion microscopy, TIRF microscopy (in vitro and in cells), RNAi depletion, domain truncation analysis, patient mutation functional characterization\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro single-molecule TIRF plus live-cell imaging, domain dissection, patient mutation tested; preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.03.20.644298\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Transcriptional regulation of KIF14 overexpression in ovarian cancer involves Sp1 and YY1 transcription factors binding to the KIF14 promoter. ChIP confirmed enrichment of Sp1 and YY1 at the endogenous KIF14 promoter in high-KIF14-expressing ovarian cancer cell lines. siRNA knockdown of Sp1 and YY1 reduced endogenous KIF14 expression. miR-93, miR-144, and miR-382 post-transcriptionally regulate KIF14 mRNA levels.\",\n      \"method\": \"Promoter deletion analysis, ChIP, siRNA knockdown, miRNA mimic/inhibitor treatment\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP for direct promoter binding plus functional siRNA knockdown, miRNA functional validation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24626475\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"KIF14 depletion reduces AKT phosphorylation, decreases GPX4 and SLC7A11 expression, increases ACSL4, and sensitizes triple-negative breast cancer cells to ferroptosis. Reciprocal co-immunoprecipitation supports a physical association between endogenous KIF14 and AKT. AKT activator SC79 partially reverses the biochemical and ferroptosis phenotypes caused by KIF14 depletion.\",\n      \"method\": \"Reciprocal co-immunoprecipitation (KIF14-AKT), RNAi knockdown, western blot, ferroptosis assays (MDA, Fe2+, ferrostatin-1 rescue), AKT activator rescue\",\n      \"journal\": \"Open life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP for physical interaction, multiple orthogonal functional assays, AKT rescue experiment, single lab\",\n      \"pmids\": [\"42083583\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KIF14 is a kinesin-3 family microtubule motor protein that localizes to the central spindle and midbody during cytokinesis by interacting with PRC1, where it recruits citron kinase (CIT-K) to enable successful cell division; its rigor-like, tight microtubule-binding motor domain supports midbody microtubule stabilization, while its intrinsically disordered N-terminal domain enables super-processivity, microtubule tip-tracking, and antiparallel microtubule sliding; beyond cytokinesis, KIF14 regulates primary ciliogenesis and IFT through Aurora A modulation, controls integrin activation by tethering the Radil-Rap1 effector on microtubules, promotes AKT phosphorylation (via physical association with AKT), transports adhesion molecules (CDH11, vinculin) to the cell membrane, and is subject to transcriptional regulation by Sp1/YY1/E2F1 and post-translational regulation including BUB1-mediated phosphorylation at Ser1292 and MYCBP2-mediated ubiquitination.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF14 is a microtubule motor that drives the completion of cytokinesis by organizing the central spindle and midbody [#0, #1]. It targets to the central spindle through interaction with PRC1 and recruits citron kinase (CIT-K/CRIK), with which it localizes codependently to the midbody to enable abscission; loss of KIF14 produces cytokinesis failure, endoreduplication, and multinucleated cells [#0, #1]. The CIT-K/KIF14 interaction is gated by mitotic kinase phosphorylation of CIT-K, coupling midbody stability to cell-cycle signaling [#17]. The motor itself is biochemically unusual: its motor domain binds microtubules tightly in a rigor-like state with robust ATPase activity but very slow motility, adopting an exceptionally twisted central β-sheet [#3], while an intrinsically disordered N-terminal domain confers super-processivity, autonomous microtubule plus-end tip-tracking, parallel microtubule crosslinking, and antiparallel microtubule sliding [#9]. Beyond division, KIF14 functions in primary ciliogenesis and intraflagellar transport, where its depletion disrupts basal body and distal appendage protein localization and deregulates Aurora A activity [#10]. KIF14 also acts in cell adhesion and migration, tethering the Radil–Rap1 effector on microtubules to restrain inside-out integrin activation [#2] and delivering adhesion cargoes such as vinculin to the leading edge to support focal adhesion assembly [#15]. Biallelic loss-of-function mutations in KIF14 cause a lethal fetal ciliopathy and primary microcephaly, with patient cells recapitulating the midbody-localization and cytokinesis defects [#6, #7]. KIF14 expression is driven transcriptionally by Sp1, YY1, and E2F1 [#19, #15], and it is widely studied as a proliferation- and migration-promoting factor across cancers.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established how KIF14 acts in cell division by placing it on the central spindle and linking it to the essential cytokinesis kinase citron kinase.\",\n      \"evidence\": \"Reciprocal endogenous Co-IP, RNAi depletion, and immunofluorescence in cultured cells, plus time-lapse imaging of cytokinesis phenotypes\",\n      \"pmids\": [\"16431929\", \"16648480\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the structural basis of midbody microtubule engagement\", \"Mechanism by which CIT-K activation state gates complex formation left undefined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Extended KIF14 function beyond mitosis by showing it scaffolds the Radil-Rap1 axis on microtubules to control integrin activation and migration.\",\n      \"evidence\": \"Co-IP and pulldown for Radil PDZ binding plus RNAi with spreading, migration, and integrin activation assays\",\n      \"pmids\": [\"23209302\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether motor activity vs. static tethering drives Radil sequestration not separated\", \"Link to the mitotic role unestablished\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined the in vivo physiological requirement for Kif14 in brain development via loss-of-function mouse and human genetics, connecting cytokinesis to neurodevelopmental disease.\",\n      \"evidence\": \"Positional cloning, knockout and transgenic rescue in mice; whole-exome sequencing and segregation in human ciliopathy families\",\n      \"pmids\": [\"23308235\", \"24128419\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not dissect which molecular activity (cytokinesis vs. cilia) drives the brain phenotype\", \"Cellular mechanism not assayed in the human genetics report\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Determined the motor's unusual mechanochemistry, revealing a rigor-like microtubule-binding state with strong ATPase but minimal motility.\",\n      \"evidence\": \"X-ray crystal structure of the ADP-bound motor domain, cryo-EM fitting, and in vitro ATPase, co-sedimentation, and motility assays (mouse motor domain)\",\n      \"pmids\": [\"24949858\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length motor behavior not addressed\", \"Functional consequence of the tight-binding state in cells not tested here\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Implicated KIF14 in cancer signaling networks, placing it upstream of SCF(Skp2)/p27 control of the cell cycle and as a promoter of AKT activation.\",\n      \"evidence\": \"RNAi, western blot, overexpression rescue for the Skp2/p27 axis; live-cell colocalization, knockdown, and small-molecule inhibition for AKT; ChIP and siRNA for Sp1/YY1 transcriptional control\",\n      \"pmids\": [\"24854087\", \"24784001\", \"24626475\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether KIF14 directly or indirectly affects Skp2/p27 not resolved\", \"Mechanism of KIF14-AKT functional coupling not defined biochemically here\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Confirmed that KIF14 loss causes primary microcephaly through failed cytokinesis, validating the disease mechanism in patient cells and knockout mice.\",\n      \"evidence\": \"Whole-exome sequencing, immunofluorescence of patient fibroblasts showing impaired KIF14/CRIK midbody localization, RNAi, and Kif14 knockout mice\",\n      \"pmids\": [\"28892560\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not test contribution of ciliary defects to microcephaly\", \"Quantitative threshold of KIF14 function required for division not defined\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Assigned distinct functional roles to KIF14's domains and discovered a ciliary function, showing the disordered N-terminus enables processivity/tip-tracking/sliding while depletion disrupts ciliogenesis via Aurora A.\",\n      \"evidence\": \"Single-molecule TIRF reconstitution with domain truncations; RNAi, imaging, Aurora A inhibition epistasis, and Hedgehog reporter assays\",\n      \"pmids\": [\"32649913\", \"32348467\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the disordered domain's in vitro activities map onto specific in-cell ciliary/mitotic functions not directly linked\", \"Aurora A-independent Hedgehog defect mechanism unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Clarified ciliary mechanism and adhesion-cargo transport, showing KIF14 runs processively along the axoneme driving IFT and delivers vinculin to the leading edge under E2F1 transcriptional control.\",\n      \"evidence\": \"Live-cell/expansion/TIRF imaging with domain and patient-mutation analysis (preprint); Co-IP for vinculin, ChIP for E2F1, and metastasis models\",\n      \"pmids\": [\"bio_10.1101_2025.03.20.644298\", \"40931756\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ciliary motility findings remain in preprint, not peer-reviewed\", \"Whether cargo transport and IFT roles share a common motor mechanism not established\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Extended post-translational regulation and signaling outputs, identifying BUB1 phosphorylation, MYCBP2 ubiquitination, and a KIF14-AKT axis modulating ferroptosis.\",\n      \"evidence\": \"Phospho-mutant rescue (Ser1292), GSEA with partial knockdown rescue for MYCBP2, and reciprocal Co-IP with AKT-activator rescue in cancer cells\",\n      \"pmids\": [\"38498903\", \"42036047\", \"42083583\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"MYCBP2-mediated ubiquitination not biochemically reconstituted\", \"Direct vs. indirect KIF14-AKT coupling unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KIF14's rigor-like, slow motor and its super-processive disordered-domain behavior are integrated into a single molecule to perform both midbody stabilization and processive ciliary/cargo transport remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No unified model linking motor mechanochemistry to its distinct cytokinetic, ciliary, and adhesion roles\", \"Structure of full-length KIF14 in cargo-bound states not determined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [3, 9, 18]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [3, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 11, 15]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3, 9]},\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [10, 18]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [5, 11, 15]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1, 7]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [10, 18]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 5, 20]},\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [2, 15]}\n    ],\n    \"complexes\": [\"central spindle/midbody\", \"KIF14-citron kinase complex\", \"KIF14-PRC1 complex\"],\n    \"partners\": [\"PRC1\", \"CIT\", \"RADIL\", \"AKT1\", \"VCL\", \"BUB1\", \"MYCBP2\", \"G3BP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}