{"gene":"KIF18B","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2011,"finding":"KIF18B forms a complex with the kinesin-13 motor MCAK, and this interaction is required for robust microtubule depolymerization. Aurora kinases negatively regulate this complex through phosphorylation of MCAK, thereby controlling microtubule plus-end stability in mitosis.","method":"Co-immunoprecipitation, loss-of-function knockdown, Aurora kinase inhibition with phenotypic readout of spindle MT stability","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP establishing complex, functional rescue experiments, replicated by multiple subsequent studies","pmids":["21820309"],"is_preprint":false},{"year":2011,"finding":"KIF18B localizes to the nucleus during interphase and, upon nuclear envelope breakdown, tracks to astral microtubule plus ends via a direct interaction with EB1 through its C-terminal domain. EB1 knockdown disrupts KIF18B targeting to MT plus ends. KIF18B knockdown causes increased astral MT number and length and spindle defects.","method":"Yeast two-hybrid screen identifying EB1 interaction; in vitro binding assay with C-terminal domain; immunofluorescence localization; siRNA knockdown with phenotypic readout","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — yeast two-hybrid plus in vitro direct binding plus cellular localization and knockdown phenotype, replicated by independent lab (PMID 21820309)","pmids":["21737685"],"is_preprint":false},{"year":2010,"finding":"KIF18B protein level is elevated at late G2 through metaphase (cell cycle-regulated), localizes predominantly to the nucleus in interphase, and associates closely with astral microtubules during prometaphase and metaphase. A nuclear localization signal was mapped by EGFP-tagged deletion mutants.","method":"Western blotting across cell cycle stages, immunocytochemistry, EGFP-tagged deletion mutants for NLS mapping","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiments with deletion mutant mapping, single lab, multiple orthogonal methods","pmids":["20600703"],"is_preprint":false},{"year":2018,"finding":"KIF18B is a highly processive plus end-directed motor that uses a C-terminal non-motor microtubule-binding region to accumulate at growing microtubule plus ends. This C-terminal region is regulated by phosphorylation to spatially control plus-end accumulation. KIF18B shortens microtubules by increasing the catastrophe rate, and this activity is essential for mitotic spindle centering.","method":"In vitro reconstitution of motor motility, gene knockout, phosphorylation-mimetic mutants, dynamic microtubule assays measuring catastrophe rate","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with single-molecule analysis, mutagenesis of phosphorylation sites, KO with defined spindle positioning phenotype","pmids":["29661912"],"is_preprint":false},{"year":2016,"finding":"KIF18B (along with MCAK) promotes bipolar spindle assembly in Eg5-independent cells by destabilizing astral microtubules; loss of KIF18B and MCAK causes excessive astral MTs that generate inward pushing forces on centrosomes inhibiting centrosome separation.","method":"Genome-wide siRNA screen in Eg5-independent cells, functional validation with knockdown and spindle assembly phenotype readout","journal":"Chromosoma","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide screen plus targeted knockdown validation, single lab, epistasis with MCAK and Aurora A defined","pmids":["27354041"],"is_preprint":false},{"year":2016,"finding":"KIF18B spatially controls astral microtubule dynamics in PtK cells; loss of KIF18B most dramatically increases lifetimes of astral microtubules extending toward the cell cortex, revealing spatial regulation of its depolymerizing activity.","method":"siRNA knockdown, EB1 plus-end tracking to measure MT dynamics spatially in mitotic cells","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live-cell EB1 tracking with spatial quantification of MT dynamics in KD cells, single lab","pmids":["27559136"],"is_preprint":false},{"year":2021,"finding":"KIF18B is constitutively chromatin-bound in the nucleus during interphase and interacts with 53BP1 through a central Tudor-interacting motif (TIM) that binds the Tudor domain of 53BP1. TIM enhances the 53BP1 Tudor domain interaction with dimethylated lysine 20 of histone H4. Both TIM and the motor function of KIF18B are required for efficient 53BP1 focal recruitment to DNA double-strand breaks and for fusion of dysfunctional telomeres.","method":"Co-immunoprecipitation identifying KIF18B–53BP1 interaction; domain mapping of TIM; mutagenesis of TIM and motor domain; γH2AX/53BP1 focus assays after DNA damage; telomere fusion assay","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, domain mutagenesis, multiple functional assays (DSB repair foci, telomere fusion), single lab but orthogonal methods","pmids":["34192545"],"is_preprint":false},{"year":2022,"finding":"Kif18b, MCAK, and the plus-end tracking protein EB3 act cooperatively in an integrated network to potently promote microtubule depolymerization at very low concentrations. Kif18b can transport EB3 and MCAK to microtubule plus ends through multivalent weak interactions, accumulating them at plus ends to drive efficient MT shortening.","method":"In vitro reconstitution with purified proteins, single-molecule imaging, total internal reflection fluorescence microscopy","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1 / Strong — full in vitro reconstitution with single-molecule imaging, mechanistic dissection of transport and accumulation activities","pmids":["35502670"],"is_preprint":false},{"year":2021,"finding":"KIF18B accumulates at the cell cortex during mitosis in keratinocytes, colocalizing with the LGN/NuMA/dynein-dynactin spindle orientation machinery, and is required for oriented cell divisions within the hair placode. Loss of KIF18B or NuMA disrupts spindle orientation and results in aberrant cell fate marker expression of hair follicle progenitor cells.","method":"Genetic KO/mutation in mouse epidermis, immunofluorescence colocalization with spindle orientation machinery, cell fate marker analysis in vivo","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with defined spindle orientation and cell fate phenotype, colocalization evidence, single lab","pmids":["34432485"],"is_preprint":false},{"year":2023,"finding":"Importin α/β interact with KIF18B and enhance its microtubule association by increasing the on-rate and decreasing the off-rate from MTs, thereby stimulating MT destabilization. EB1 promotes MT destabilization without increasing lattice binding, indicating that EB1 and importin α/β have distinct regulatory roles. Blocking importin α/β interaction disrupts KIF18B localization without affecting aster size, while blocking EB1 interaction disrupts MT plus-end accumulation.","method":"In vitro MT binding/motility assays with purified importins, residue-specific mutagenesis of binding sites, cell-based localization and monopolar spindle assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with kinetic analysis plus mutagenesis plus cellular functional readouts, single lab but multiple orthogonal approaches","pmids":["36790918"],"is_preprint":false},{"year":2019,"finding":"KIF18B binds to the promoter region of CDCA8 and activates its transcription in pancreatic ductal adenocarcinoma cells, promoting cell proliferation.","method":"Chromatin immunoprecipitation (ChIP) showing KIF18B binding to CDCA8 promoter; knockdown with cell proliferation and cell cycle readouts","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — ChIP showing promoter binding, single lab, mechanistic follow-up limited","pmids":["31875977"],"is_preprint":false},{"year":2020,"finding":"KIF18B regulates β-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2, and at the post-transcriptional level by interacting with APC (adenomatous polyposis coli tumor suppressor) in osteosarcoma cells.","method":"Western blot for ATF2 nuclear localization, co-immunoprecipitation with APC, knockdown with β-catenin readout","journal":"Cancer biology & medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP with APC and indirect nuclear ATF2 measurement, single lab, limited mechanistic validation","pmids":["32587775"],"is_preprint":false},{"year":2021,"finding":"KIF18b promotes expression of PARPBP (PARP-1 binding protein) in oxaliplatin-resistant colorectal cancer cells by directly interacting with SP1 and thereby attenuating SP1-mediated recruitment of DNMT3b to the PARPBP promoter, reducing promoter methylation and de-repressing PARPBP transcription.","method":"Co-immunoprecipitation of KIF18b with SP1; methylation analysis of PARPBP promoter; knockdown experiments with DNMT3b and SP1 interaction readouts","journal":"Experimental cell research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP, single lab, limited mechanistic orthogonal validation in abstract","pmids":["34508743"],"is_preprint":false},{"year":2023,"finding":"KIF18B loss counteracts vincristine-induced p53 response, suggesting that KIF18B is required for the mitotic surveillance pathway (USP28-53BP1-p53) signaling. CRISPR/Cas9 knockout of KIF18B induces vincristine resistance across two DLBCL cell lines.","method":"Genome-wide CRISPR screen; CRISPR/Cas9 KO in two cell lines; p53 pathway readout after vincristine treatment","journal":"British journal of haematology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR screen plus KO validation in two cell lines with defined p53 pathway mechanistic readout, single lab","pmids":["37190875"],"is_preprint":false},{"year":2026,"finding":"KIF18B interacts with ATR (confirmed by co-immunoprecipitation) and stabilizes ATR/CHK1 DNA damage signaling in oxaliplatin-resistant esophageal squamous cell carcinoma; KIF18B knockdown suppresses p-ATR and p-CHK1, increases γH2AX foci, and reverses oxaliplatin resistance.","method":"Co-immunoprecipitation confirming KIF18B–ATR interaction; knockdown with p-ATR/p-CHK1/γH2AX readouts; in vivo xenograft with oxaliplatin combination","journal":"Molecular genetics and genomics : MGG","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP reported in abstract, single lab, limited orthogonal mechanistic validation","pmids":["42201394"],"is_preprint":false},{"year":2026,"finding":"KIF18B regulates Skp2 protein stability through the ubiquitin-proteasome system: KIF18B knockdown accelerates Skp2 ubiquitination and reduces Skp2 protein levels, inhibiting glycolytic metabolism and osteosarcoma cell viability; KIF18B overexpression enhances glycolysis in an Skp2-dependent manner.","method":"Knockdown/overexpression with Skp2 ubiquitination assay, glycolysis metabolic readouts, rescue experiments with Skp2","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — ubiquitination assay and rescue experiments, single lab, abstract-level detail only","pmids":["41977416"],"is_preprint":false},{"year":2026,"finding":"KIF18B depletion downregulates E2F target genes and reduces E2F2 promoter activity (confirmed by luciferase reporter assay); overexpression of E2F1, E2F2, or E2F3 rescues the proliferation defect induced by KIF18B loss in lung adenocarcinoma cells, placing KIF18B upstream of the E2F transcriptional network.","method":"Transcriptomic analysis after KIF18B knockdown; luciferase reporter assay for E2F activity; rescue by E2F overexpression","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — luciferase reporter with epistatic rescue by E2F overexpression, single lab, mechanistic placement upstream of E2F pathway","pmids":["41751942"],"is_preprint":false}],"current_model":"KIF18B is a kinesin-8 family motor protein that tracks processively to microtubule plus ends via interactions with EB1 (and EB3) through its C-terminal domain, uses its motor activity to reach plus ends where it promotes microtubule catastrophe, and forms a cooperative complex with the kinesin-13 MCAK and EB proteins to potently depolymerize astral microtubules during mitosis; this complex activity is spatially regulated by Aurora kinase-mediated phosphorylation of MCAK and by importin α/β modulation of KIF18B microtubule affinity, with KIF18B being required for mitotic spindle centering, oriented cell division, and—via a Tudor-interacting motif—for 53BP1-mediated DNA double-strand break repair during interphase."},"narrative":{"mechanistic_narrative":"KIF18B is a kinesin-8 family plus end-directed motor that controls microtubule dynamics during mitosis by promoting microtubule catastrophe, principally at astral microtubules where it sets spindle position and centering [PMID:29661912, PMID:27559136]. It is a highly processive motor that accumulates at growing microtubule plus ends through a C-terminal non-motor microtubule-binding region whose plus-end targeting is governed by direct interaction with the end-binding protein EB1; EB1 knockdown abolishes KIF18B plus-end tracking and KIF18B loss yields excessive, lengthened astral microtubules and spindle defects [PMID:21737685, PMID:29661912]. Its depolymerizing output is delivered through a cooperative network with the kinesin-13 MCAK and EB3: KIF18B transports MCAK and EB3 to plus ends via multivalent weak interactions, enabling potent microtubule shortening at low concentrations, with Aurora kinase phosphorylation of MCAK negatively regulating this complex [PMID:21820309, PMID:35502670]. This activity is spatially tuned by phosphorylation of the KIF18B C-terminus and by importin α/β, which increase its microtubule lattice on-rate and decrease its off-rate to stimulate destabilization, a regulatory input distinct from that of EB1 [PMID:29661912, PMID:36790918]. Through astral microtubule destabilization KIF18B promotes bipolar spindle assembly and, by accumulating at the cell cortex with the LGN/NuMA/dynein-dynactin machinery, directs oriented cell division in vivo [PMID:27354041, PMID:34432485]. KIF18B has a separable interphase role: it is constitutively chromatin-bound and, through a central Tudor-interacting motif that binds the 53BP1 Tudor domain and enhances its recognition of H4K20me2, is required—together with its motor function—for 53BP1 focal recruitment to DNA double-strand breaks and telomere fusion [PMID:34192545]. In cancer contexts KIF18B is reported to support proliferation, glycolysis, and chemoresistance through transcriptional and signaling effects, but these activities are heterogeneous across the corpus and not yet mechanistically unified [PMID:37190875, PMID:41751942].","teleology":[{"year":2010,"claim":"Established KIF18B as a cell-cycle-regulated, predominantly nuclear interphase protein that associates with astral microtubules in mitosis, defining when and where it acts.","evidence":"Western blotting across the cell cycle, immunocytochemistry, and EGFP-deletion NLS mapping","pmids":["20600703"],"confidence":"Medium","gaps":["No molecular activity assigned at this stage","Mechanism of astral MT association not defined"]},{"year":2011,"claim":"Resolved how KIF18B reaches microtubule plus ends and what it does there, identifying the EB1 interaction via the C-terminal domain and a depolymerizing/destabilizing role on astral microtubules.","evidence":"Yeast two-hybrid, in vitro C-terminal binding assay, immunofluorescence, and siRNA knockdown phenotypes; reciprocal MCAK Co-IP and Aurora inhibition in a parallel study","pmids":["21737685","21820309"],"confidence":"High","gaps":["Did not reconstitute the motor activity in vitro","Quantitative contribution of MCAK vs KIF18B to depolymerization unresolved"]},{"year":2016,"claim":"Showed that KIF18B-driven astral MT destabilization is spatially biased and functionally required for bipolar spindle assembly and centrosome separation.","evidence":"Genome-wide siRNA screen in Eg5-independent cells and spatial EB1 plus-end tracking of MT dynamics in knockdown cells","pmids":["27354041","27559136"],"confidence":"Medium","gaps":["Molecular basis of spatial bias toward cortex-directed MTs not defined","Single-lab phenotypes"]},{"year":2018,"claim":"Established KIF18B as a highly processive motor that increases catastrophe rate, with its C-terminal MT-binding region phosphoregulated to control plus-end accumulation, directly linking motor activity to spindle centering.","evidence":"In vitro reconstitution of single-molecule motility, dynamic MT catastrophe assays, phospho-mimetic mutants, and knockout with spindle positioning readout","pmids":["29661912"],"confidence":"High","gaps":["Identity of the kinase(s) acting on the C-terminus not defined here","How catastrophe induction couples to centering forces not fully resolved"]},{"year":2021,"claim":"Uncovered a mitosis-independent interphase function: KIF18B promotes 53BP1 recruitment to DSBs and telomere fusion via a Tudor-interacting motif that augments 53BP1 binding to H4K20me2.","evidence":"Reciprocal Co-IP, TIM and motor-domain mutagenesis, γH2AX/53BP1 focus assays, and telomere fusion assay","pmids":["34192545"],"confidence":"High","gaps":["Why a microtubule motor function is needed for nuclear DSB repair is unexplained","No structure of the TIM–Tudor interaction"]},{"year":2021,"claim":"Connected KIF18B's MT-depolymerizing activity to tissue-level outcomes by showing it localizes to the mitotic cortex with the LGN/NuMA/dynein-dynactin machinery and is required for oriented division and correct cell fate in vivo.","evidence":"Mouse epidermal genetic KO, colocalization with spindle orientation machinery, and cell fate marker analysis","pmids":["34432485"],"confidence":"Medium","gaps":["Direct biochemical link between KIF18B and the LGN/NuMA complex not established","Whether cortical accumulation is depolymerization-dependent unresolved"]},{"year":2022,"claim":"Reconstituted the depolymerization mechanism, demonstrating that KIF18B transports EB3 and MCAK to plus ends through multivalent weak interactions to drive potent MT shortening at low concentrations.","evidence":"In vitro reconstitution with purified proteins, single-molecule and TIRF imaging","pmids":["35502670"],"confidence":"High","gaps":["Stoichiometry of the KIF18B–EB3–MCAK assembly in cells not defined","Cooperativity with phosphoregulation not integrated"]},{"year":2023,"claim":"Distinguished two regulatory inputs to KIF18B MT binding, showing importin α/β raise lattice affinity (on-rate up, off-rate down) to stimulate destabilization while EB1 promotes destabilization without increasing lattice binding.","evidence":"In vitro MT binding/motility kinetics with purified importins, residue-specific mutagenesis, and cellular localization/monopolar spindle assays","pmids":["36790918"],"confidence":"High","gaps":["How the RanGTP gradient spatially patterns importin regulation in cells not directly shown","Crosstalk between importin and phospho-regulation unresolved"]},{"year":2023,"claim":"Linked KIF18B to the mitotic surveillance/p53 pathway, showing its loss blunts vincristine-induced p53 response and confers resistance in lymphoma cells.","evidence":"Genome-wide CRISPR screen and CRISPR/Cas9 KO in two DLBCL cell lines with p53 pathway readout","pmids":["37190875"],"confidence":"Medium","gaps":["Whether the effect depends on the 53BP1 interaction or motor activity not dissected","Mechanism connecting KIF18B to USP28-53BP1-p53 not directly tested"]},{"year":2026,"claim":"Reported additional cancer-context roles placing KIF18B upstream of E2F transcriptional activity, with weaker evidence for Skp2 stabilization/glycolysis, ATR/CHK1 signaling, and other transcriptional effects.","evidence":"Knockdown transcriptomics with luciferase E2F reporter and E2F rescue; ubiquitination/glycolysis assays; Co-IP with ATR/APC/SP1 and promoter analyses","pmids":["41751942","41977416","42201394","31875977","32587775","34508743"],"confidence":"Medium","gaps":["Several rest on single Co-IPs without reciprocal validation","Relationship to the established mitotic/DSB functions not reconciled","Largely abstract-level mechanistic detail"]},{"year":null,"claim":"How KIF18B's spatially restricted depolymerizing activity, its phospho/importin/EB1 regulatory inputs, and its nuclear 53BP1-dependent DSB role are coordinated within one protein remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model integrating motor, EB-binding, and TIM regions","Kinase(s) controlling the C-terminus not identified in the corpus","Mechanistic basis for diverse cancer phenotypes not unified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[3,7]},{"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":[1,3,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[6,7]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2,6]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,3,5]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[8]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[6]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,3,4,8]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[6]}],"complexes":["KIF18B-MCAK-EB3 depolymerization complex"],"partners":["MCAK","EB1","EB3","53BP1","KPNA (IMPORTIN ALPHA)","KPNB1 (IMPORTIN BETA)","NUMA","ATR"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86Y91","full_name":"Kinesin-like protein KIF18B","aliases":[],"length_aa":852,"mass_kda":93.0,"function":"In complex with KIF2C, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells. Its major role may be to transport KIF2C and/or MAPRE1 along microtubules","subcellular_location":"Nucleus; Cytoplasm; Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q86Y91/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF18B","classification":"Common Essential","n_dependent_lines":497,"n_total_lines":1208,"dependency_fraction":0.41142384105960267},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"KPNB1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KIF18B","total_profiled":1310},"omim":[{"mim_id":"614570","title":"KINESIN FAMILY MEMBER 18B; KIF18B","url":"https://www.omim.org/entry/614570"},{"mim_id":"604538","title":"KINESIN FAMILY MEMBER 2C; KIF2C","url":"https://www.omim.org/entry/604538"},{"mim_id":"603108","title":"MICROTUBULE-ASSOCIATED PROTEIN, RP/EB FAMILY, MEMBER 1; MAPRE1","url":"https://www.omim.org/entry/603108"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Microtubule ends","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Nuclear bodies","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"bone marrow","ntpm":11.9},{"tissue":"lymphoid tissue","ntpm":13.4}],"url":"https://www.proteinatlas.org/search/KIF18B"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q86Y91","domains":[{"cath_id":"3.40.850.10","chopping":"5-45_66-363","consensus_level":"high","plddt":88.496,"start":5,"end":363}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86Y91","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86Y91-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86Y91-F1-predicted_aligned_error_v6.png","plddt_mean":62.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIF18B","jax_strain_url":"https://www.jax.org/strain/search?query=KIF18B"},"sequence":{"accession":"Q86Y91","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86Y91.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86Y91/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86Y91"}},"corpus_meta":[{"pmid":"21820309","id":"PMC_21820309","title":"A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases.","date":"2011","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/21820309","citation_count":114,"is_preprint":false},{"pmid":"21737685","id":"PMC_21737685","title":"Kif18B interacts with EB1 and controls astral microtubule length during mitosis.","date":"2011","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/21737685","citation_count":85,"is_preprint":false},{"pmid":"29636620","id":"PMC_29636620","title":"KIF18B promotes tumor progression through activating the Wnt/β-catenin pathway in cervical cancer.","date":"2018","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/29636620","citation_count":58,"is_preprint":false},{"pmid":"25236463","id":"PMC_25236463","title":"Translating bioinformatics in oncology: guilt-by-profiling analysis and identification of KIF18B and CDCA3 as novel driver genes in carcinogenesis.","date":"2014","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/25236463","citation_count":53,"is_preprint":false},{"pmid":"29661912","id":"PMC_29661912","title":"Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning.","date":"2018","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/29661912","citation_count":52,"is_preprint":false},{"pmid":"20600703","id":"PMC_20600703","title":"Cell cycle-regulated expression and subcellular localization of a kinesin-8 member human KIF18B.","date":"2010","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/20600703","citation_count":41,"is_preprint":false},{"pmid":"32052444","id":"PMC_32052444","title":"KIF18B promotes hepatocellular carcinoma progression through activating Wnt/β-catenin-signaling pathway.","date":"2020","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32052444","citation_count":37,"is_preprint":false},{"pmid":"27354041","id":"PMC_27354041","title":"Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation.","date":"2016","source":"Chromosoma","url":"https://pubmed.ncbi.nlm.nih.gov/27354041","citation_count":32,"is_preprint":false},{"pmid":"31875977","id":"PMC_31875977","title":"KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8.","date":"2019","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/31875977","citation_count":29,"is_preprint":false},{"pmid":"32587775","id":"PMC_32587775","title":"KIF18B promotes tumor progression in osteosarcoma by activating β-catenin.","date":"2020","source":"Cancer biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32587775","citation_count":24,"is_preprint":false},{"pmid":"27559136","id":"PMC_27559136","title":"Spatial regulation of astral microtubule dynamics by Kif18B in PtK cells.","date":"2016","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/27559136","citation_count":23,"is_preprint":false},{"pmid":"34192545","id":"PMC_34192545","title":"The nuclear kinesin KIF18B promotes 53BP1-mediated DNA double-strand break repair.","date":"2021","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/34192545","citation_count":19,"is_preprint":false},{"pmid":"31759406","id":"PMC_31759406","title":"KIF18B as a regulator in microtubule movement accelerates tumor progression and triggers poor outcome in lung adenocarcinoma.","date":"2019","source":"Tissue & cell","url":"https://pubmed.ncbi.nlm.nih.gov/31759406","citation_count":18,"is_preprint":false},{"pmid":"35251343","id":"PMC_35251343","title":"KIF18B promotes breast cancer cell proliferation, migration and invasion by targeting TRIP13 and activating the Wnt/β-catenin signaling pathway.","date":"2022","source":"Oncology 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Cancers","date":"2025-05-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.14.653945","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18005,"output_tokens":4121,"usd":0.057915,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":12131,"output_tokens":3937,"usd":0.07954,"stage2_stop_reason":"end_turn"},"total_usd":0.137455,"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\": 2011,\n      \"finding\": \"KIF18B forms a complex with the kinesin-13 motor MCAK, and this interaction is required for robust microtubule depolymerization. Aurora kinases negatively regulate this complex through phosphorylation of MCAK, thereby controlling microtubule plus-end stability in mitosis.\",\n      \"method\": \"Co-immunoprecipitation, loss-of-function knockdown, Aurora kinase inhibition with phenotypic readout of spindle MT stability\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP establishing complex, functional rescue experiments, replicated by multiple subsequent studies\",\n      \"pmids\": [\"21820309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"KIF18B localizes to the nucleus during interphase and, upon nuclear envelope breakdown, tracks to astral microtubule plus ends via a direct interaction with EB1 through its C-terminal domain. EB1 knockdown disrupts KIF18B targeting to MT plus ends. KIF18B knockdown causes increased astral MT number and length and spindle defects.\",\n      \"method\": \"Yeast two-hybrid screen identifying EB1 interaction; in vitro binding assay with C-terminal domain; immunofluorescence localization; siRNA knockdown with phenotypic readout\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — yeast two-hybrid plus in vitro direct binding plus cellular localization and knockdown phenotype, replicated by independent lab (PMID 21820309)\",\n      \"pmids\": [\"21737685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"KIF18B protein level is elevated at late G2 through metaphase (cell cycle-regulated), localizes predominantly to the nucleus in interphase, and associates closely with astral microtubules during prometaphase and metaphase. A nuclear localization signal was mapped by EGFP-tagged deletion mutants.\",\n      \"method\": \"Western blotting across cell cycle stages, immunocytochemistry, EGFP-tagged deletion mutants for NLS mapping\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiments with deletion mutant mapping, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"20600703\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KIF18B is a highly processive plus end-directed motor that uses a C-terminal non-motor microtubule-binding region to accumulate at growing microtubule plus ends. This C-terminal region is regulated by phosphorylation to spatially control plus-end accumulation. KIF18B shortens microtubules by increasing the catastrophe rate, and this activity is essential for mitotic spindle centering.\",\n      \"method\": \"In vitro reconstitution of motor motility, gene knockout, phosphorylation-mimetic mutants, dynamic microtubule assays measuring catastrophe rate\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with single-molecule analysis, mutagenesis of phosphorylation sites, KO with defined spindle positioning phenotype\",\n      \"pmids\": [\"29661912\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KIF18B (along with MCAK) promotes bipolar spindle assembly in Eg5-independent cells by destabilizing astral microtubules; loss of KIF18B and MCAK causes excessive astral MTs that generate inward pushing forces on centrosomes inhibiting centrosome separation.\",\n      \"method\": \"Genome-wide siRNA screen in Eg5-independent cells, functional validation with knockdown and spindle assembly phenotype readout\",\n      \"journal\": \"Chromosoma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide screen plus targeted knockdown validation, single lab, epistasis with MCAK and Aurora A defined\",\n      \"pmids\": [\"27354041\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KIF18B spatially controls astral microtubule dynamics in PtK cells; loss of KIF18B most dramatically increases lifetimes of astral microtubules extending toward the cell cortex, revealing spatial regulation of its depolymerizing activity.\",\n      \"method\": \"siRNA knockdown, EB1 plus-end tracking to measure MT dynamics spatially in mitotic cells\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live-cell EB1 tracking with spatial quantification of MT dynamics in KD cells, single lab\",\n      \"pmids\": [\"27559136\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KIF18B is constitutively chromatin-bound in the nucleus during interphase and interacts with 53BP1 through a central Tudor-interacting motif (TIM) that binds the Tudor domain of 53BP1. TIM enhances the 53BP1 Tudor domain interaction with dimethylated lysine 20 of histone H4. Both TIM and the motor function of KIF18B are required for efficient 53BP1 focal recruitment to DNA double-strand breaks and for fusion of dysfunctional telomeres.\",\n      \"method\": \"Co-immunoprecipitation identifying KIF18B–53BP1 interaction; domain mapping of TIM; mutagenesis of TIM and motor domain; γH2AX/53BP1 focus assays after DNA damage; telomere fusion assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, domain mutagenesis, multiple functional assays (DSB repair foci, telomere fusion), single lab but orthogonal methods\",\n      \"pmids\": [\"34192545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Kif18b, MCAK, and the plus-end tracking protein EB3 act cooperatively in an integrated network to potently promote microtubule depolymerization at very low concentrations. Kif18b can transport EB3 and MCAK to microtubule plus ends through multivalent weak interactions, accumulating them at plus ends to drive efficient MT shortening.\",\n      \"method\": \"In vitro reconstitution with purified proteins, single-molecule imaging, total internal reflection fluorescence microscopy\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — full in vitro reconstitution with single-molecule imaging, mechanistic dissection of transport and accumulation activities\",\n      \"pmids\": [\"35502670\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KIF18B accumulates at the cell cortex during mitosis in keratinocytes, colocalizing with the LGN/NuMA/dynein-dynactin spindle orientation machinery, and is required for oriented cell divisions within the hair placode. Loss of KIF18B or NuMA disrupts spindle orientation and results in aberrant cell fate marker expression of hair follicle progenitor cells.\",\n      \"method\": \"Genetic KO/mutation in mouse epidermis, immunofluorescence colocalization with spindle orientation machinery, cell fate marker analysis in vivo\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with defined spindle orientation and cell fate phenotype, colocalization evidence, single lab\",\n      \"pmids\": [\"34432485\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Importin α/β interact with KIF18B and enhance its microtubule association by increasing the on-rate and decreasing the off-rate from MTs, thereby stimulating MT destabilization. EB1 promotes MT destabilization without increasing lattice binding, indicating that EB1 and importin α/β have distinct regulatory roles. Blocking importin α/β interaction disrupts KIF18B localization without affecting aster size, while blocking EB1 interaction disrupts MT plus-end accumulation.\",\n      \"method\": \"In vitro MT binding/motility assays with purified importins, residue-specific mutagenesis of binding sites, cell-based localization and monopolar spindle assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with kinetic analysis plus mutagenesis plus cellular functional readouts, single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"36790918\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"KIF18B binds to the promoter region of CDCA8 and activates its transcription in pancreatic ductal adenocarcinoma cells, promoting cell proliferation.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP) showing KIF18B binding to CDCA8 promoter; knockdown with cell proliferation and cell cycle readouts\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ChIP showing promoter binding, single lab, mechanistic follow-up limited\",\n      \"pmids\": [\"31875977\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF18B regulates β-catenin expression at the transcriptional level by controlling nuclear aggregation of ATF2, and at the post-transcriptional level by interacting with APC (adenomatous polyposis coli tumor suppressor) in osteosarcoma cells.\",\n      \"method\": \"Western blot for ATF2 nuclear localization, co-immunoprecipitation with APC, knockdown with β-catenin readout\",\n      \"journal\": \"Cancer biology & medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP with APC and indirect nuclear ATF2 measurement, single lab, limited mechanistic validation\",\n      \"pmids\": [\"32587775\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KIF18b promotes expression of PARPBP (PARP-1 binding protein) in oxaliplatin-resistant colorectal cancer cells by directly interacting with SP1 and thereby attenuating SP1-mediated recruitment of DNMT3b to the PARPBP promoter, reducing promoter methylation and de-repressing PARPBP transcription.\",\n      \"method\": \"Co-immunoprecipitation of KIF18b with SP1; methylation analysis of PARPBP promoter; knockdown experiments with DNMT3b and SP1 interaction readouts\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP, single lab, limited mechanistic orthogonal validation in abstract\",\n      \"pmids\": [\"34508743\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KIF18B loss counteracts vincristine-induced p53 response, suggesting that KIF18B is required for the mitotic surveillance pathway (USP28-53BP1-p53) signaling. CRISPR/Cas9 knockout of KIF18B induces vincristine resistance across two DLBCL cell lines.\",\n      \"method\": \"Genome-wide CRISPR screen; CRISPR/Cas9 KO in two cell lines; p53 pathway readout after vincristine treatment\",\n      \"journal\": \"British journal of haematology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR screen plus KO validation in two cell lines with defined p53 pathway mechanistic readout, single lab\",\n      \"pmids\": [\"37190875\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"KIF18B interacts with ATR (confirmed by co-immunoprecipitation) and stabilizes ATR/CHK1 DNA damage signaling in oxaliplatin-resistant esophageal squamous cell carcinoma; KIF18B knockdown suppresses p-ATR and p-CHK1, increases γH2AX foci, and reverses oxaliplatin resistance.\",\n      \"method\": \"Co-immunoprecipitation confirming KIF18B–ATR interaction; knockdown with p-ATR/p-CHK1/γH2AX readouts; in vivo xenograft with oxaliplatin combination\",\n      \"journal\": \"Molecular genetics and genomics : MGG\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP reported in abstract, single lab, limited orthogonal mechanistic validation\",\n      \"pmids\": [\"42201394\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"KIF18B regulates Skp2 protein stability through the ubiquitin-proteasome system: KIF18B knockdown accelerates Skp2 ubiquitination and reduces Skp2 protein levels, inhibiting glycolytic metabolism and osteosarcoma cell viability; KIF18B overexpression enhances glycolysis in an Skp2-dependent manner.\",\n      \"method\": \"Knockdown/overexpression with Skp2 ubiquitination assay, glycolysis metabolic readouts, rescue experiments with Skp2\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ubiquitination assay and rescue experiments, single lab, abstract-level detail only\",\n      \"pmids\": [\"41977416\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"KIF18B depletion downregulates E2F target genes and reduces E2F2 promoter activity (confirmed by luciferase reporter assay); overexpression of E2F1, E2F2, or E2F3 rescues the proliferation defect induced by KIF18B loss in lung adenocarcinoma cells, placing KIF18B upstream of the E2F transcriptional network.\",\n      \"method\": \"Transcriptomic analysis after KIF18B knockdown; luciferase reporter assay for E2F activity; rescue by E2F overexpression\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — luciferase reporter with epistatic rescue by E2F overexpression, single lab, mechanistic placement upstream of E2F pathway\",\n      \"pmids\": [\"41751942\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KIF18B is a kinesin-8 family motor protein that tracks processively to microtubule plus ends via interactions with EB1 (and EB3) through its C-terminal domain, uses its motor activity to reach plus ends where it promotes microtubule catastrophe, and forms a cooperative complex with the kinesin-13 MCAK and EB proteins to potently depolymerize astral microtubules during mitosis; this complex activity is spatially regulated by Aurora kinase-mediated phosphorylation of MCAK and by importin α/β modulation of KIF18B microtubule affinity, with KIF18B being required for mitotic spindle centering, oriented cell division, and—via a Tudor-interacting motif—for 53BP1-mediated DNA double-strand break repair during interphase.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF18B is a kinesin-8 family plus end-directed motor that controls microtubule dynamics during mitosis by promoting microtubule catastrophe, principally at astral microtubules where it sets spindle position and centering [#3, #5]. It is a highly processive motor that accumulates at growing microtubule plus ends through a C-terminal non-motor microtubule-binding region whose plus-end targeting is governed by direct interaction with the end-binding protein EB1; EB1 knockdown abolishes KIF18B plus-end tracking and KIF18B loss yields excessive, lengthened astral microtubules and spindle defects [#1, #3]. Its depolymerizing output is delivered through a cooperative network with the kinesin-13 MCAK and EB3: KIF18B transports MCAK and EB3 to plus ends via multivalent weak interactions, enabling potent microtubule shortening at low concentrations, with Aurora kinase phosphorylation of MCAK negatively regulating this complex [#0, #7]. This activity is spatially tuned by phosphorylation of the KIF18B C-terminus and by importin α/β, which increase its microtubule lattice on-rate and decrease its off-rate to stimulate destabilization, a regulatory input distinct from that of EB1 [#3, #9]. Through astral microtubule destabilization KIF18B promotes bipolar spindle assembly and, by accumulating at the cell cortex with the LGN/NuMA/dynein-dynactin machinery, directs oriented cell division in vivo [#4, #8]. KIF18B has a separable interphase role: it is constitutively chromatin-bound and, through a central Tudor-interacting motif that binds the 53BP1 Tudor domain and enhances its recognition of H4K20me2, is required—together with its motor function—for 53BP1 focal recruitment to DNA double-strand breaks and telomere fusion [#6]. In cancer contexts KIF18B is reported to support proliferation, glycolysis, and chemoresistance through transcriptional and signaling effects, but these activities are heterogeneous across the corpus and not yet mechanistically unified [#13, #16].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Established KIF18B as a cell-cycle-regulated, predominantly nuclear interphase protein that associates with astral microtubules in mitosis, defining when and where it acts.\",\n      \"evidence\": \"Western blotting across the cell cycle, immunocytochemistry, and EGFP-deletion NLS mapping\",\n      \"pmids\": [\"20600703\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular activity assigned at this stage\", \"Mechanism of astral MT association not defined\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Resolved how KIF18B reaches microtubule plus ends and what it does there, identifying the EB1 interaction via the C-terminal domain and a depolymerizing/destabilizing role on astral microtubules.\",\n      \"evidence\": \"Yeast two-hybrid, in vitro C-terminal binding assay, immunofluorescence, and siRNA knockdown phenotypes; reciprocal MCAK Co-IP and Aurora inhibition in a parallel study\",\n      \"pmids\": [\"21737685\", \"21820309\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not reconstitute the motor activity in vitro\", \"Quantitative contribution of MCAK vs KIF18B to depolymerization unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Showed that KIF18B-driven astral MT destabilization is spatially biased and functionally required for bipolar spindle assembly and centrosome separation.\",\n      \"evidence\": \"Genome-wide siRNA screen in Eg5-independent cells and spatial EB1 plus-end tracking of MT dynamics in knockdown cells\",\n      \"pmids\": [\"27354041\", \"27559136\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of spatial bias toward cortex-directed MTs not defined\", \"Single-lab phenotypes\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Established KIF18B as a highly processive motor that increases catastrophe rate, with its C-terminal MT-binding region phosphoregulated to control plus-end accumulation, directly linking motor activity to spindle centering.\",\n      \"evidence\": \"In vitro reconstitution of single-molecule motility, dynamic MT catastrophe assays, phospho-mimetic mutants, and knockout with spindle positioning readout\",\n      \"pmids\": [\"29661912\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the kinase(s) acting on the C-terminus not defined here\", \"How catastrophe induction couples to centering forces not fully resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Uncovered a mitosis-independent interphase function: KIF18B promotes 53BP1 recruitment to DSBs and telomere fusion via a Tudor-interacting motif that augments 53BP1 binding to H4K20me2.\",\n      \"evidence\": \"Reciprocal Co-IP, TIM and motor-domain mutagenesis, γH2AX/53BP1 focus assays, and telomere fusion assay\",\n      \"pmids\": [\"34192545\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why a microtubule motor function is needed for nuclear DSB repair is unexplained\", \"No structure of the TIM–Tudor interaction\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Connected KIF18B's MT-depolymerizing activity to tissue-level outcomes by showing it localizes to the mitotic cortex with the LGN/NuMA/dynein-dynactin machinery and is required for oriented division and correct cell fate in vivo.\",\n      \"evidence\": \"Mouse epidermal genetic KO, colocalization with spindle orientation machinery, and cell fate marker analysis\",\n      \"pmids\": [\"34432485\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical link between KIF18B and the LGN/NuMA complex not established\", \"Whether cortical accumulation is depolymerization-dependent unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Reconstituted the depolymerization mechanism, demonstrating that KIF18B transports EB3 and MCAK to plus ends through multivalent weak interactions to drive potent MT shortening at low concentrations.\",\n      \"evidence\": \"In vitro reconstitution with purified proteins, single-molecule and TIRF imaging\",\n      \"pmids\": [\"35502670\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of the KIF18B–EB3–MCAK assembly in cells not defined\", \"Cooperativity with phosphoregulation not integrated\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Distinguished two regulatory inputs to KIF18B MT binding, showing importin α/β raise lattice affinity (on-rate up, off-rate down) to stimulate destabilization while EB1 promotes destabilization without increasing lattice binding.\",\n      \"evidence\": \"In vitro MT binding/motility kinetics with purified importins, residue-specific mutagenesis, and cellular localization/monopolar spindle assays\",\n      \"pmids\": [\"36790918\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the RanGTP gradient spatially patterns importin regulation in cells not directly shown\", \"Crosstalk between importin and phospho-regulation unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Linked KIF18B to the mitotic surveillance/p53 pathway, showing its loss blunts vincristine-induced p53 response and confers resistance in lymphoma cells.\",\n      \"evidence\": \"Genome-wide CRISPR screen and CRISPR/Cas9 KO in two DLBCL cell lines with p53 pathway readout\",\n      \"pmids\": [\"37190875\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the effect depends on the 53BP1 interaction or motor activity not dissected\", \"Mechanism connecting KIF18B to USP28-53BP1-p53 not directly tested\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Reported additional cancer-context roles placing KIF18B upstream of E2F transcriptional activity, with weaker evidence for Skp2 stabilization/glycolysis, ATR/CHK1 signaling, and other transcriptional effects.\",\n      \"evidence\": \"Knockdown transcriptomics with luciferase E2F reporter and E2F rescue; ubiquitination/glycolysis assays; Co-IP with ATR/APC/SP1 and promoter analyses\",\n      \"pmids\": [\"41751942\", \"41977416\", \"42201394\", \"31875977\", \"32587775\", \"34508743\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Several rest on single Co-IPs without reciprocal validation\", \"Relationship to the established mitotic/DSB functions not reconciled\", \"Largely abstract-level mechanistic detail\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KIF18B's spatially restricted depolymerizing activity, its phospho/importin/EB1 regulatory inputs, and its nuclear 53BP1-dependent DSB role are coordinated within one protein remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model integrating motor, EB-binding, and TIM regions\", \"Kinase(s) controlling the C-terminus not identified in the corpus\", \"Mechanistic basis for diverse cancer phenotypes not unified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [3, 7]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 3, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [6, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2, 6]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 3, 5]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 3, 4, 8]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [\n      \"KIF18B-MCAK-EB3 depolymerization complex\"\n    ],\n    \"partners\": [\n      \"MCAK\",\n      \"EB1\",\n      \"EB3\",\n      \"53BP1\",\n      \"KPNA (importin alpha)\",\n      \"KPNB1 (importin beta)\",\n      \"NuMA\",\n      \"ATR\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}