{"gene":"KIF23","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":1995,"finding":"PLK (Plk1) physically interacts with CHO1/MKLP-1 in vivo, co-localizes with it at the midbody during telophase/cytokinesis, and phosphorylates CHO1/MKLP-1 in vitro via Plk-associated kinase activity.","method":"Co-immunoprecipitation, co-localization by immunofluorescence, in vitro kinase assay","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and in vitro kinase assay in single lab; later confirmed by Liu et al. 2004","pmids":["8524282"],"is_preprint":false},{"year":2004,"finding":"Plk1 binds CHO1/MKLP-1 through its Polo-box domain, while the stalk domain of CHO1/MKLP-1 mediates binding to Plk1. Ser904 and Ser905 are the two major Plk1 phosphorylation sites on CHO1/MKLP-1. Depletion of CHO1/MKLP-1 mislocalizes Plk1 during late mitosis. A non-phosphorylatable CHO1 mutant causes cytokinesis defects, and rescue of CHO1-depletion-induced multinucleation requires the phosphorylatable form.","method":"Transient transfection, domain-deletion analysis, vector-based RNAi, site-directed mutagenesis, rescue experiments","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (domain mapping, mutagenesis of phosphosites, RNAi depletion, rescue) in single lab; replicates and extends earlier Plk1/MKLP1 interaction finding","pmids":["15199097"],"is_preprint":false},{"year":2005,"finding":"Aurora B phosphorylates ZEN-4/MKLP1 in vitro and in vivo on conserved C-terminal serine residues. A non-phosphorylatable ZEN-4 mutant localizes properly but fails to support completion of cytokinesis in C. elegans embryos. Inhibition of aurora B in late anaphase in mammalian cells attenuates MKLP1 phosphorylation and causes cytokinesis defects without disrupting the central spindle.","method":"In vitro kinase assay, in vivo phosphorylation (C. elegans and human cells), phospho-mutant analysis, aurora kinase inhibitor treatment","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro kinase assay plus in vivo validation plus phospho-mutant functional analysis across two species","pmids":["15854913"],"is_preprint":false},{"year":2005,"finding":"INCENP is required for recruiting MKLP1 to the spindle midzone/midbody. Depletion of MKLP1 by siRNA does not cause chromosome segregation or midzone formation defects, but abrogates midbody formation and completion of cytokinesis. INCENP-mediated recruitment of MKLP1 to the midzone/midbody is a crucial step for midbody formation.","method":"RNAi/siRNA knockdown, immunofluorescence, 3D live-cell imaging reconstruction","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal imaging methods plus functional RNAi depletion in single lab","pmids":["15796717"],"is_preprint":false},{"year":2007,"finding":"Centralspindlin is a heterotetrameric complex consisting of two CYK-4/MgcRacGAP homodimers and two ZEN-4/MKLP1 homodimers (each subunit dimerizing via parallel coiled coils) assembled through two low-affinity interactions. The assembled centralspindlin complex, but not individual subunits alone, is sufficient to bundle microtubules in vitro.","method":"Biochemical reconstitution, in vitro microtubule bundling assay, genetic epistasis (suppressor screen with second-site mutations), co-immunoprecipitation","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution in vitro plus mutagenesis plus genetic suppressor analysis; replicated across species contexts","pmids":["17942600"],"is_preprint":false},{"year":1999,"finding":"Activated (GTP-bound) Arf proteins bind directly to an 88-amino-acid domain in the C-terminal tail of MKLP1. This interaction is GTP-dependent and maps to the switch I and switch II regions of Arf3. All human Arf isoforms interact with the MKLP1 C-terminal domain.","method":"Yeast two-hybrid screen, GST pulldown assay, deletion mapping, Arf3 point-mutation screen","journal":"Cell motility and the cytoskeleton","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus GST pulldown plus mutagenesis in single lab","pmids":["10506747"],"is_preprint":false},{"year":2012,"finding":"Arf6 directly interacts with MKLP1 to form a 2:2 heterotetramer. Crystal structure reveals an extended β-sheet spanning the entire heterotetramer, suitable for interaction with concave membrane surfaces at the cleavage furrow. Arf6 first accumulates around the cleavage furrow, then is recruited to the Flemming body via MKLP1. Structure-based mutagenesis and siRNA knockdown show complex formation is required for completion of cytokinesis.","method":"Crystal structure determination, structure-based mutagenesis, siRNA knockdown, live-cell imaging","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus functional mutagenesis plus siRNA validation in single rigorous study","pmids":["22522702"],"is_preprint":false},{"year":2013,"finding":"TRAF6 mediates K63-linked ubiquitination of the midbody ring-localized protein KIF23/MKLP1. This ubiquitination is important for recognition by ubiquitin-binding autophagy receptors SQSTM1/p62 and NBR1 (together with WDFY3/ALFY) and subsequent degradation of midbody ring derivatives by selective autophagy.","method":"siRNA depletion, ubiquitination assay, co-immunoprecipitation, immunofluorescence","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus ubiquitination assay plus functional depletion in single lab","pmids":["24128730"],"is_preprint":false},{"year":2013,"finding":"A missense mutation c.2747C>G (p.P916R) in KIF23 causes autosomal dominant congenital dyserythropoietic anemia type III (CDA III). RNAi knockdown and rescue experiments in HeLa cells demonstrated that the p.P916R mutation causes cytokinesis failure, consistent with the large multinucleated erythroblasts observed in CDA III patients.","method":"Next-generation resequencing, haplotype analysis, RNAi knockdown and rescue in HeLa cells, functional cytokinesis assay","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic identification plus functional rescue experiment; segregation confirmed in two independent families","pmids":["23570799"],"is_preprint":false},{"year":1998,"finding":"CHO1/MKLP1 is associated with microtubules in podocytes and is required for establishing nonuniform (mixed) microtubule polarity. Antisense oligonucleotide-mediated depletion of CHO1/MKLP1 in differentiating podocytes abolished process formation and the nonuniform polarity of microtubules, demonstrating that MKLP1-dependent microtubule polarity is necessary for process formation.","method":"Antisense oligonucleotide treatment, hook-decoration of microtubules (polarity assay), taxol/nocodazole recovery experiments, immunolocalization","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — antisense depletion with specific phenotypic readout plus MT polarity assay in single lab","pmids":["9864367"],"is_preprint":false},{"year":1998,"finding":"CHO1/MKLP1 is expressed in postmitotic neurons including hippocampal, cortical, and cerebellar neurons. Expression peaks prior to dendritic development and decreases afterward. Dorsal root ganglion neurons that form axons but not dendrites express significantly lower levels, consistent with a role for MKLP1 in establishing the nonuniform microtubule polarity characteristic of dendrites.","method":"In situ hybridization (rodent brain sections), mRNA expression analysis in cultured neurons","journal":"The European journal of neuroscience","confidence":"Low","confidence_rationale":"Tier 3 / Weak — expression/localization only, no direct functional manipulation in this paper","pmids":["9749792"],"is_preprint":false},{"year":2004,"finding":"ZEN-4/MKLP1 functions postmitotically to establish foregut epithelium polarity in C. elegans. zen-4 mutants express polarity markers but fail to target PAR-3/Bazooka, PKC-3/aPKC, HMR-1/cadherin, and AJM-1 to correct cortical domains, and show disorganized microtubules and actin, indicating MKLP1 regulates an early step in epithelial polarization.","method":"Genetic mutant analysis, immunofluorescence of polarity markers, confocal microscopy in C. elegans","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with multiple defined molecular readouts in C. elegans model","pmids":["15182666"],"is_preprint":false},{"year":2006,"finding":"Two nuclear localization signals (NLSs) in the tail domain of Mklp-1 were mapped to residues 899SRKRRSST906 and 949KRKKP953. Ectopic expression of an NLS-deleted mutant causes cell cycle arrest at cytokinesis. Phosphomimetic mutation of two serine residues in the first NLS (S→D) attenuates nuclear localization, suggesting NLS activity is regulated by phosphorylation.","method":"Deletion/mutation mapping, ectopic expression, fluorescence microscopy, cell cycle analysis","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mapping plus functional mutant analysis with specific cytokinesis arrest readout in single lab","pmids":["17198681"],"is_preprint":false},{"year":1999,"finding":"The C-terminal domain of MKLP-1 contains at least one nuclear localization sequence; C-terminal constructs fused to GFP localize to the nucleus in HeLa cells and remain tightly associated with the nucleus following detergent and salt extraction, indicating stable interaction with a nuclear component.","method":"GFP-fusion expression in HeLa cells, subcellular fractionation, fluorescence microscopy","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single localization method, no functional manipulation","pmids":["10403813"],"is_preprint":false},{"year":2006,"finding":"The motor domain and tail domain of MKLP1 are both required for dendritic targeting in hippocampal neurons. Deletion of the motor domain prevents dendritic distribution; deletion of the tail domain causes axonal mis-targeting; deletion of the stalk domain does not affect dendritic specificity.","method":"GFP-tagged domain deletion constructs expressed in primary hippocampal neurons, fluorescence microscopy","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic domain-deletion mapping with clear localization readouts in primary neurons","pmids":["16418225"],"is_preprint":false},{"year":2013,"finding":"p53 transcriptionally represses KIF23 mRNA and protein expression. This repression is mediated through the CDK inhibitor p21(WAF1/CIP1) and requires a cell cycle genes homology region (CHR) element in the KIF23 promoter. Cell cycle- and p53-dependent regulation of KIF23 involves differential binding of DREAM and MMB complexes to the CHR element.","method":"Promoter-reporter assays, chromatin immunoprecipitation (DREAM/MMB binding to CHR), siRNA knockdown of p21, RT-PCR and western blot","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (ChIP, reporter assays, siRNA) in single lab","pmids":["23650552"],"is_preprint":false},{"year":2008,"finding":"CUX1 and E2F1 cooperatively regulate KIF23/MKLP1 transcription at S-phase entry. Both transcription factors bind the MKLP1 promoter (demonstrated by ChIP) upon S-phase entry via CHR elements and E2F binding elements. Overexpression of either E2F1 or CUX1 increases endogenous MKLP1 levels; siRNA knockdown or dominant-negative E2F1 reduces expression.","method":"Chromatin immunoprecipitation, promoter-luciferase reporter assays, siRNA knockdown, overexpression","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus reporter assays plus functional knockdown/overexpression in single lab","pmids":["19015243"],"is_preprint":false},{"year":2015,"finding":"The two LATS/NDR kinase consensus sites (S716 and S814) in the long Kif23/CHO1 isoform are phosphorylated by NDR and LATS kinases in vitro. LATS1/2 contribute to S814 phosphorylation in vivo. Phosphorylation of the upstream S716 site is required for efficient phosphorylation at S814, revealing sequential phosphorylation. S814 phosphorylation constitutes a 14-3-3 binding site involved in Kif23 clustering during cytokinesis, and this modification is absent in post-abscission midbodies.","method":"In vitro kinase assay, site-directed mutagenesis, in vivo phosphorylation assay, 14-3-3 binding assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro kinase reconstitution plus mutagenesis plus in vivo validation; single lab","pmids":["25658096"],"is_preprint":false},{"year":2016,"finding":"In Drosophila motoneurons, the Toll-6 receptor–dSARM–FoxO signaling pathway represses expression of Pavarotti/MKLP1 (the Drosophila ortholog). Elevated Pavarotti/MKLP1 attenuates microtubule dynamics. Toll-6-FoxO signaling promotes MT dynamics by limiting Pav-KLP expression, and this pathway is essential for axon transport and activity-dependent structural plasticity in motoneurons.","method":"Genetic epistasis (Drosophila pathway mutants), genetic suppression, in vivo imaging of MT dynamics, overexpression of Pav-KLP","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis plus in vivo imaging plus rescue experiment in Drosophila model","pmids":["27502486"],"is_preprint":false},{"year":2013,"finding":"v-Src induces cytokinesis failure by delocalizing Mklp1 from the spindle midzone. Aurora B, which regulates Mklp1 localization, and Mklp2 (responsible for Aurora B relocation from chromosomes to midzone) are also delocalized from the spindle midzone upon v-Src expression, placing Mklp1 downstream of the v-Src-Aurora B-Mklp2 axis.","method":"Inducible v-Src expression, flow cytometry, time-lapse microscopy, immunofluorescence localization","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — inducible expression system with multiple localization and cell division readouts in single lab","pmids":["23562843"],"is_preprint":false},{"year":2016,"finding":"p120-catenin (p120) binds directly to MKLP1 and to RhoA at the cleavage furrow during anaphase. The N-terminal coiled-coil domain of p120 isoform 1A is required for MKLP1 binding. p120 spatially controls RhoA GTPase cycling through concomitant binding to RhoA and MKLP1, and loss of p120 leads to multinucleation.","method":"Co-immunoprecipitation, immunofluorescence (cleavage furrow enrichment), domain deletion analysis, siRNA knockdown","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP plus domain mapping plus functional knockdown in single lab","pmids":["28004812"],"is_preprint":false},{"year":2020,"finding":"The tail domain of MKLP1 exhibits an autoinhibitory effect on its motor activity. Overexpression of the tail domain alone blocks cytokinesis and causes bi-/multinucleation. PAK2 (p21-activated kinase 2) binds to the MKLP1 tail domain (confirmed by GST pulldown, LC-MS/MS, co-IP, and FRET). PAK2 knockdown by siRNA mislocalizes MKLP1 from the midbody and impedes cytokinesis, suggesting PAK2 relieves MKLP1 autoinhibition to promote cytokinesis.","method":"GST pulldown followed by LC-MS/MS, co-immunoprecipitation, FRET, siRNA knockdown, overexpression","journal":"BioMed research international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — paper subsequently retracted (PMID 38550036); findings are unreliable","pmids":["33204722","38550036"],"is_preprint":false},{"year":2022,"finding":"The centralspindlin complex (Cyk4/Mklp1) and its interacting partner RhoGEF Ect2 are required for exclusion of NuMA/dynein/dynactin from the equatorial cell membrane during anaphase. The equatorial membrane enrichment of the Ect2/Cyk4/Mklp1 complex is essential for NuMA/dynein/dynactin exclusion and proper spindle elongation, linking centralspindlin to coordination of spindle elongation with cleavage furrow formation.","method":"siRNA depletion, live-cell imaging (membrane compartmentalization), immunofluorescence","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple depletions with quantitative imaging readouts in single lab","pmids":["36197340"],"is_preprint":false},{"year":2020,"finding":"KIF23 directly interacts with APC membrane recruitment 1 (Amer1) protein. This interaction displaces Amer1 from the membrane/cytoplasm to the nucleus and blocks Amer1's association with APC, thereby attenuating Amer1's negative regulation of Wnt/β-catenin signaling and promoting nuclear β-catenin accumulation.","method":"Co-immunoprecipitation, immunofluorescence (subcellular localization of Amer1), functional rescue experiments, western blot","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP demonstrating direct binding plus localization shift plus functional consequences in single lab","pmids":["32365332"],"is_preprint":false},{"year":2024,"finding":"SIRT7 interacts with KIF23 and inhibits succinylation of KIF23 at lysine K537. SIRT7-mediated desuccinylation enhances the protein stability of KIF23, and SIRT7 overexpression promotes anaplastic thyroid cancer cell viability and migration partly via KIF23.","method":"Co-immunoprecipitation, western blot for succinylation, overexpression/silencing in HEK-293T and ATC cells, cell viability/migration assays","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus site-specific PTM assay plus functional rescue in single lab","pmids":["38360598"],"is_preprint":false},{"year":2023,"finding":"FOXM1 epigenetically activates KIF23 expression by increasing RNA polymerase II and histone H3K27 acetylation at the KIF23 promoter. Downregulation of FOXM1 reduces KIF23 levels and alleviates sorafenib resistance in hepatocellular carcinoma cells.","method":"ChIP for RNA pol II and H3K27ac at KIF23 promoter, siRNA knockdown, western blot, drug resistance assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP plus functional knockdown with defined epigenetic mechanism in single lab","pmids":["36940637"],"is_preprint":false},{"year":2024,"finding":"KIF23 knockdown in embryonic mouse cortex causes precocious neurogenesis and neuronal apoptosis, attributed to accelerated cell cycle exit from disrupted mitotic spindle orientation and impaired cytokinesis. KIF23 depletion also perturbs apical surface structure of neural stem and progenitor cells by affecting localization of apical junction proteins. Wild-type human KIF23 rescues these phenotypes, but a microcephaly-associated KIF23 variant does not.","method":"In utero electroporation knockdown in mice, immunofluorescence, live imaging, rescue with wild-type vs. variant human KIF23","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo loss-of-function with multiple cellular phenotype readouts plus allele-specific rescue experiment","pmids":["39632980"],"is_preprint":false},{"year":2002,"finding":"Zebrafish Mklp1 redistributes from spindle microtubules at metaphase to the spindle midzone during anaphase and concentrates in the midbody during telophase/cytokinesis. Nuclear targeting is conferred by two basic motifs in the COOH terminus. Dominant-negative Mklp1 variants in one- or two-cell zebrafish embryos cause failure to complete cytokinesis, resulting in multinucleated blastomeres.","method":"GFP-tagging and live imaging in zebrafish embryos, dominant-negative mRNA injection, fractionation","journal":"Physiological genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging plus dominant-negative functional experiment in vertebrate model","pmids":["11842131"],"is_preprint":false},{"year":2022,"finding":"NAT10-mediated ac4C modification of KIF23 mRNA at its 3'UTR region stabilizes KIF23 mRNA and elevates KIF23 protein levels, which in turn activates the Wnt/β-catenin pathway to promote colorectal cancer progression. GSK-3β negatively regulates NAT10 forming a feedback loop.","method":"RIP-seq, acRIP-seq, RNA immunoprecipitation, luciferase reporter assay, siRNA knockdown, xenograft models","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple RNA biochemistry methods plus functional in vivo validation in single lab","pmids":["36522719"],"is_preprint":false},{"year":2019,"finding":"Neddylation inhibition by MLN4924 causes premature accumulation of MKLP1 at the cleavage furrow during mitosis, which is associated with increased abscission delay and failure. NEDD8 and CSN subunits localize to the midbody and cleavage furrow, indicating neddylation/deneddylation regulation at the midbody controls MKLP1 timing.","method":"MLN4924 drug treatment in synchronized cells, fixed and live-cell microscopy, immunofluorescence","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — pharmacological inhibition with localization readout, no direct mechanistic link established between neddylation and MKLP1","pmids":["31057046"],"is_preprint":false},{"year":2026,"finding":"The C-terminal domain of KIF23 directly binds to the myosin tail domain of MYH9. This interaction stabilizes MYH9 by recruiting deubiquitinase USP7, which removes K48-linked ubiquitin chains from MYH9. Elevated MYH9 then promotes recruitment of USP15 to deubiquitinate MCM2 at K469, preventing MCM2 degradation and enabling MCM2-PCNA interaction to promote cell cycle progression and cisplatin resistance in cervical cancer.","method":"Co-immunoprecipitation, protein half-life assays, ubiquitination assays, CRISPR/Cas9 knockout, site-directed mutagenesis","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus ubiquitination assays plus site-specific mutagenesis in single lab","pmids":["41940421"],"is_preprint":false},{"year":2025,"finding":"In cardiac fibroblasts, Kif23 promotes fibrosis by activating the RhoA/ROCK1 signaling axis, which suppresses Ces1d-mediated fatty acid β-oxidation, leading to lipid accumulation and myofibroblast transdifferentiation. Kif23 knockdown in vivo (post-MI mouse model) improved cardiac function and attenuated fibrosis.","method":"Proteomic profiling of knockdown vs. overexpression fibroblasts, adeno-associated virus shRNA knockdown in vivo, western blot, lipid droplet analysis, echocardiography","journal":"Hypertension","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomics plus in vivo loss-of-function with defined downstream effector (Ces1d) in single lab","pmids":["41078122"],"is_preprint":false},{"year":2025,"finding":"ETV5 transcription factor directly binds to the KIF23 promoter region (within 1–700 bp upstream of the transcription start site) and represses KIF23 transcription. ETV5 overexpression suppresses caspase-3/GSDME-mediated pyroptosis and cognitive impairment in a perioperative neurocognitive disorder model, and this protective effect is neutralized by KIF23 overexpression.","method":"Chromatin immunoprecipitation (ETV5 binding to KIF23 promoter), AAV9-mediated overexpression/knockdown in mice, western blot, cognitive behavior assays","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP demonstrating direct promoter binding plus in vivo functional rescue/reversal in single lab","pmids":["40983152"],"is_preprint":false},{"year":2021,"finding":"SHCBP1 interacts with KIF23 via its Nesd homology domain (NHD) and this interaction is important for KIF23's nuclear localization. SHCBP1 positively modulates KIF23 expression. KIF23 knockdown abrogates cisplatin resistance induced by SHCBP1 overexpression, placing KIF23 downstream of SHCBP1 in modulating cisplatin resistance.","method":"Co-immunoprecipitation (domain mapping), siRNA knockdown, overexpression, drug sensitivity assays","journal":"Head & neck","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP plus functional knockdown without in vitro reconstitution","pmids":["34918847"],"is_preprint":false},{"year":2025,"finding":"CDK1 and Aurora B phosphorylate two serine residues (S440 and S699) on Citron kinase (CIT-K), and phosphorylation at either residue reduces the ability of CIT-K to interact with its midbody partners including KIF23/MKLP1, thereby regulating midbody formation and stability.","method":"In vitro kinase assay, phospho-mutant analysis, co-immunoprecipitation, live-cell imaging","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 2 / Weak — rigorous preprint with in vitro assay and mutagenesis but not yet peer-reviewed; KIF23 is one of multiple partners, not the primary subject","pmids":[],"is_preprint":true}],"current_model":"KIF23/MKLP1 is a kinesin-6 motor protein that forms the centralspindlin heterotetrameric complex with CYK-4/MgcRacGAP; this complex bundles antiparallel midzone microtubules during anaphase, is recruited to the midbody via INCENP, and drives cytokinesis completion through regulation by Aurora B phosphorylation (on conserved C-terminal serines), Plk1 phosphorylation (on Ser904/905 via a Polo-box–stalk domain interaction), LATS/NDR-mediated sequential phosphorylation (S716→S814) creating a 14-3-3 binding site, and Arf6 binding to its C-terminal tail; TRAF6-mediated ubiquitination of MKLP1 at the post-abscission midbody ring marks it for selective autophagy; in neurons, MKLP1 establishes nonuniform microtubule polarity in dendrites via its motor and tail domains; loss-of-function mutations cause cytokinesis failure manifesting as congenital dyserythropoietic anemia type III and microcephaly; and in cancer contexts KIF23 activates oncogenic signaling (Wnt/β-catenin, PI3K/AKT, RhoA/ROCK1) through direct protein interactions (Amer1, MYH9) and is transcriptionally regulated by p53/DREAM, MMB/FOXM1, and epigenetic mechanisms."},"narrative":{"mechanistic_narrative":"KIF23/MKLP1 is a kinesin-6 motor protein that drives the completion of cytokinesis by organizing the antiparallel microtubules of the anaphase central spindle and midbody [PMID:17942600]. It assembles into the heterotetrameric centralspindlin complex with CYK-4/MgcRacGAP, and only the intact complex—not the individual subunits—bundles microtubules in vitro [PMID:17942600]; this complex also coordinates spindle elongation with furrow ingression by excluding NuMA/dynein/dynactin from the equatorial membrane together with the RhoGEF Ect2 [PMID:36197340]. MKLP1 is recruited to the spindle midzone and midbody via INCENP, a step required for midbody formation but not for chromosome segregation [PMID:15796717]. Its activity is gated by a layered phosphoregulatory program: Aurora B phosphorylates conserved C-terminal serines to license cytokinesis completion [PMID:15854913], Plk1 binds through its Polo-box to the MKLP1 stalk and phosphorylates Ser904/Ser905, with MKLP1 in turn governing Plk1 localization in late mitosis [PMID:8524282, PMID:15199097], and sequential LATS/NDR phosphorylation at S716 then S814 creates a 14-3-3 binding site controlling MKLP1 clustering [PMID:25658096]. The C-terminal tail mediates additional regulatory contacts, binding GTP-loaded Arf6 to form a membrane-apposed 2:2 heterotetramer required for abscission [PMID:10506747, PMID:22522702] and p120-catenin to spatially control RhoA cycling at the furrow [PMID:28004812]; after abscission, TRAF6-mediated K63 ubiquitination marks the midbody-ring pool for clearance by selective autophagy [PMID:24128730]. Beyond division, MKLP1 acts postmitotically to establish the nonuniform microtubule polarity of dendrites through its motor and tail domains [PMID:16418225] and to organize epithelial polarity [PMID:15182666], and it is required in the developing cortex for proper spindle orientation and progenitor cytokinesis [PMID:39632980]. A missense KIF23 mutation (p.P916R) causes autosomal dominant congenital dyserythropoietic anemia type III through cytokinesis failure [PMID:23570799], and a microcephaly-associated variant fails to rescue cortical neurogenesis defects [PMID:39632980]. In cancer, KIF23 is induced by FOXM1 and CUX1/E2F1 and repressed by the p53/p21/DREAM axis [PMID:23650552, PMID:19015243, PMID:36940637], and it promotes oncogenic Wnt/β-catenin signaling by sequestering Amer1 and stabilizing MYH9 to drive proliferation and drug resistance [PMID:32365332, PMID:41940421].","teleology":[{"year":1995,"claim":"Established that MKLP1 is a physical and enzymatic target of a mitotic kinase, opening the question of how its cytokinetic function is regulated.","evidence":"Co-IP, co-localization, and in vitro kinase assay with Plk1 in mammalian cells","pmids":["8524282"],"confidence":"Medium","gaps":["Phosphosites not mapped","Functional consequence of phosphorylation undefined"]},{"year":1998,"claim":"Showed MKLP1 has a postmitotic function in establishing mixed microtubule polarity, separating its role from cell division.","evidence":"Antisense depletion plus hook-decoration MT polarity assay in podocytes; expression profiling in neurons","pmids":["9864367","9749792"],"confidence":"Medium","gaps":["Molecular mechanism of polarity establishment unresolved","Neuronal expression data correlative only"]},{"year":1999,"claim":"Identified the C-terminal tail as a regulatory/interaction module by mapping Arf binding and nuclear localization activity.","evidence":"Yeast two-hybrid, GST pulldown, Arf3 mutagenesis; GFP-fusion fractionation in HeLa","pmids":["10506747","10403813"],"confidence":"Medium","gaps":["Physiological role of Arf binding not established here","Nuclear component bound by NLS unidentified"]},{"year":2004,"claim":"Defined the Plk1-MKLP1 interaction at domain and residue resolution and showed reciprocal dependence for cytokinesis, establishing MKLP1 as both Plk1 substrate and localization scaffold.","evidence":"Domain mapping, phosphosite mutagenesis (Ser904/905), RNAi depletion and rescue; C. elegans epithelial polarity genetics","pmids":["15199097","15182666"],"confidence":"High","gaps":["How Ser904/905 phosphorylation alters molecular activity unclear","Link between Plk1 mislocalization and abscission failure mechanistic detail missing"]},{"year":2005,"claim":"Identified Aurora B as a cytokinesis-licensing kinase for MKLP1 and INCENP as its midzone/midbody recruitment factor, defining the recruitment-and-activation logic.","evidence":"In vitro kinase assay plus phospho-mutant analysis in C. elegans and human cells; RNAi plus 3D imaging for INCENP dependence","pmids":["15854913","15796717"],"confidence":"High","gaps":["Precise C-terminal serines not all enumerated","How phosphorylation drives abscission completion not mechanistically resolved"]},{"year":2007,"claim":"Established the heterotetrameric architecture of centralspindlin and showed that complex assembly, not isolated subunits, confers microtubule-bundling, defining the minimal functional unit.","evidence":"Biochemical reconstitution, in vitro bundling assay, genetic suppressor screen, co-IP","pmids":["17942600"],"confidence":"High","gaps":["Structural basis of bundling not determined","Regulation of assembly in cells incomplete"]},{"year":2012,"claim":"Provided a structural mechanism for membrane engagement at the cleavage furrow through the MKLP1-Arf6 heterotetramer.","evidence":"Crystal structure, structure-based mutagenesis, siRNA, live imaging","pmids":["22522702"],"confidence":"High","gaps":["Coordination of Arf6 binding with motor activity unresolved","Upstream control of Arf6 GTP loading at furrow undefined"]},{"year":2013,"claim":"Connected MKLP1 to human disease and post-abscission turnover, showing a point mutation causes CDA III via cytokinesis failure and that TRAF6 ubiquitination targets the midbody ring for autophagy.","evidence":"Genetic identification plus RNAi rescue in HeLa (p.P916R); ubiquitination assay, co-IP, autophagy receptor analysis; p53/p21/DREAM transcriptional regulation; v-Src delocalization","pmids":["23570799","24128730","23650552","23562843"],"confidence":"High","gaps":["How p.P916R perturbs molecular function unclear","Trigger for midbody-ring ubiquitination in normal cells undefined"]},{"year":2015,"claim":"Revealed a sequential LATS/NDR phosphorylation switch that creates a 14-3-3 binding site controlling MKLP1 clustering during cytokinesis.","evidence":"In vitro kinase assay, S716/S814 mutagenesis, in vivo phosphorylation, 14-3-3 binding assay","pmids":["25658096"],"confidence":"Medium","gaps":["How clustering relates to bundling/abscission unresolved","Isoform-specificity of long CHO1 form in vivo unclear"]},{"year":2016,"claim":"Demonstrated MKLP1 partners with p120-catenin to spatially control RhoA cycling at the furrow and is transcriptionally limited in neurons by Toll-6/dSARM/FoxO signaling.","evidence":"Reciprocal co-IP, domain mapping, siRNA (p120); Drosophila genetic epistasis and MT-dynamics imaging (Toll-6/FoxO)","pmids":["28004812","27502486"],"confidence":"Medium","gaps":["Mechanism by which MKLP1 modulates RhoA GAP/GEF activity unclear","Direct vs. indirect transcriptional control of MKLP1 by FoxO undefined"]},{"year":2022,"claim":"Extended centralspindlin function to membrane compartmentalization, showing it excludes NuMA/dynein/dynactin from the equatorial membrane to coordinate spindle elongation with furrowing; cancer studies linked KIF23 mRNA stability to oncogenic Wnt signaling.","evidence":"siRNA depletion plus live imaging (membrane exclusion); RIP-seq/acRIP-seq and xenografts for NAT10-mediated ac4C modification","pmids":["36197340","36522719"],"confidence":"Medium","gaps":["Direct molecular basis of NuMA exclusion unresolved","Relationship between cytokinetic and oncogenic functions unclear"]},{"year":2024,"claim":"Established a developmental cortical requirement for KIF23 with allele-specific causality for microcephaly, and identified PTM-mediated stability control via SIRT7 desuccinylation.","evidence":"In utero electroporation knockdown plus rescue with WT vs. microcephaly variant; co-IP and site-specific succinylation assays (SIRT7/K537)","pmids":["39632980","38360598"],"confidence":"High","gaps":["Whether cortical phenotype reflects cytokinesis vs. spindle orientation defects not fully separated","Generality of K537 succinylation across tissues unknown"]},{"year":2025,"claim":"Expanded KIF23 oncogenic and fibrotic signaling, linking it to MYH9 stabilization, RhoA/ROCK1-driven fibrosis, and transcriptional repression by ETV5.","evidence":"Co-IP, ubiquitination assays, CRISPR knockout (MYH9/USP7/MCM2); proteomics and in vivo shRNA (cardiac fibrosis); ChIP and AAV9 rescue (ETV5)","pmids":["41940421","41078122","40983152"],"confidence":"Medium","gaps":["Whether motor activity is required for signaling functions unclear","Direct vs. scaffold roles in deubiquitinase recruitment not separated"]},{"year":null,"claim":"How the layered phosphorylation, ubiquitination, and PTM inputs are integrated to time MKLP1 motor activity and centralspindlin assembly during abscission, and how its cytokinetic versus signaling roles are mechanistically partitioned, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified structural model of regulated MKLP1 motor activation","Tail autoinhibition mechanism unestablished in reliable literature","Causal separation of cytokinetic and oncogenic signaling functions lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[4,14]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[4,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,20,23]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[4,9]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[12,13,27]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[6,20]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2,3,4,8]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[23,31]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[14,26]}],"complexes":["centralspindlin"],"partners":["RACGAP1","PLK1","AURKB","INCENP","ARF6","CTNND1","AMER1","MYH9"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q02241","full_name":"Kinesin-like protein KIF23","aliases":["Kinesin-like protein 5","Mitotic kinesin-like protein 1"],"length_aa":960,"mass_kda":110.1,"function":"Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Essential for cytokinesis in Rho-mediated signaling. Required for the localization of ECT2 to the central spindle. Plus-end-directed motor enzyme that moves antiparallel microtubules in vitro","subcellular_location":"Nucleus; Cytoplasm, cytoskeleton, spindle; Midbody, Midbody ring; Midbody","url":"https://www.uniprot.org/uniprotkb/Q02241/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF23","classification":"Common Essential","n_dependent_lines":1201,"n_total_lines":1208,"dependency_fraction":0.9942052980132451},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CALM3","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KIF23","total_profiled":1310},"omim":[{"mim_id":"621035","title":"PROLINE-RICH PROTEIN 14-LIKE PROTEIN; PRR14L","url":"https://www.omim.org/entry/621035"},{"mim_id":"619789","title":"ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE IIIb, AUTOSOMAL RECESSIVE; CDAN3B","url":"https://www.omim.org/entry/619789"},{"mim_id":"613466","title":"PREFOLDIN 2; PFDN2","url":"https://www.omim.org/entry/613466"},{"mim_id":"613465","title":"NME/NM23 FAMILY, MEMBER 7; NME7","url":"https://www.omim.org/entry/613465"},{"mim_id":"612632","title":"USHER SYNDROME, TYPE IH; USH1H","url":"https://www.omim.org/entry/612632"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Midbody ring","reliability":"Additional"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Mid piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"},{"location":"Annulus","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":20.4},{"tissue":"lymphoid tissue","ntpm":14.8}],"url":"https://www.proteinatlas.org/search/KIF23"},"hgnc":{"alias_symbol":["MKLP1","MKLP-1"],"prev_symbol":["KNSL5"]},"alphafold":{"accession":"Q02241","domains":[{"cath_id":"3.40.850.10","chopping":"30-177_199-422","consensus_level":"high","plddt":87.5758,"start":30,"end":422},{"cath_id":"2.60.40.4330","chopping":"820-825_838-896","consensus_level":"high","plddt":86.2255,"start":820,"end":896},{"cath_id":"1.20.5","chopping":"543-601","consensus_level":"medium","plddt":95.0954,"start":543,"end":601}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q02241","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q02241-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q02241-F1-predicted_aligned_error_v6.png","plddt_mean":72.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIF23","jax_strain_url":"https://www.jax.org/strain/search?query=KIF23"},"sequence":{"accession":"Q02241","fasta_url":"https://rest.uniprot.org/uniprotkb/Q02241.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q02241/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q02241"}},"corpus_meta":[{"pmid":"8524282","id":"PMC_8524282","title":"Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1.","date":"1995","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8524282","citation_count":246,"is_preprint":false},{"pmid":"15854913","id":"PMC_15854913","title":"Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis.","date":"2005","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/15854913","citation_count":179,"is_preprint":false},{"pmid":"36522719","id":"PMC_36522719","title":"Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA.","date":"2022","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/36522719","citation_count":134,"is_preprint":false},{"pmid":"17942600","id":"PMC_17942600","title":"Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/17942600","citation_count":95,"is_preprint":false},{"pmid":"15796717","id":"PMC_15796717","title":"Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells.","date":"2005","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/15796717","citation_count":82,"is_preprint":false},{"pmid":"21904957","id":"PMC_21904957","title":"Downregulation of KIF23 suppresses glioma proliferation.","date":"2011","source":"Journal of neuro-oncology","url":"https://pubmed.ncbi.nlm.nih.gov/21904957","citation_count":80,"is_preprint":false},{"pmid":"26775597","id":"PMC_26775597","title":"Overexpression of KIF23 predicts clinical outcome in primary lung cancer patients.","date":"2015","source":"Lung cancer (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/26775597","citation_count":79,"is_preprint":false},{"pmid":"15199097","id":"PMC_15199097","title":"Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1.","date":"2004","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15199097","citation_count":78,"is_preprint":false},{"pmid":"23570799","id":"PMC_23570799","title":"Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23.","date":"2013","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/23570799","citation_count":74,"is_preprint":false},{"pmid":"36894036","id":"PMC_36894036","title":"A Therapeutically Targetable TAZ-TEAD2 Pathway Drives the Growth of Hepatocellular Carcinoma via ANLN and KIF23.","date":"2023","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/36894036","citation_count":62,"is_preprint":false},{"pmid":"10506747","id":"PMC_10506747","title":"Arf proteins bind to mitotic kinesin-like protein 1 (MKLP1) in a GTP-dependent fashion.","date":"1999","source":"Cell motility and the cytoskeleton","url":"https://pubmed.ncbi.nlm.nih.gov/10506747","citation_count":58,"is_preprint":false},{"pmid":"22522702","id":"PMC_22522702","title":"Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis.","date":"2012","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/22522702","citation_count":51,"is_preprint":false},{"pmid":"24128730","id":"PMC_24128730","title":"TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy.","date":"2013","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/24128730","citation_count":48,"is_preprint":false},{"pmid":"31007778","id":"PMC_31007778","title":"KIF23 Promotes Gastric Cancer by Stimulating Cell Proliferation.","date":"2019","source":"Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/31007778","citation_count":46,"is_preprint":false},{"pmid":"15182666","id":"PMC_15182666","title":"ZEN-4/MKLP1 is required to polarize the foregut epithelium.","date":"2004","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/15182666","citation_count":45,"is_preprint":false},{"pmid":"9864367","id":"PMC_9864367","title":"Nonuniform microtubular polarity established by CHO1/MKLP1 motor protein is necessary for process formation of podocytes.","date":"1998","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9864367","citation_count":45,"is_preprint":false},{"pmid":"23650552","id":"PMC_23650552","title":"p53 and cell cycle dependent transcription of kinesin family member 23 (KIF23) is controlled via a CHR promoter element bound by DREAM and MMB complexes.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23650552","citation_count":45,"is_preprint":false},{"pmid":"19015243","id":"PMC_19015243","title":"CUX1 and E2F1 regulate coordinated expression of the mitotic complex genes Ect2, MgcRacGAP, and MKLP1 in S phase.","date":"2008","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19015243","citation_count":43,"is_preprint":false},{"pmid":"27212033","id":"PMC_27212033","title":"An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma.","date":"2016","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/27212033","citation_count":39,"is_preprint":false},{"pmid":"31135262","id":"PMC_31135262","title":"Methylation-mediated repression of MiR-424/503 cluster promotes proliferation and migration of ovarian cancer cells through targeting the hub gene KIF23.","date":"2019","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/31135262","citation_count":38,"is_preprint":false},{"pmid":"33313139","id":"PMC_33313139","title":"KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target.","date":"2020","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33313139","citation_count":37,"is_preprint":false},{"pmid":"27502486","id":"PMC_27502486","title":"A Toll receptor-FoxO pathway represses Pavarotti/MKLP1 to promote microtubule dynamics in motoneurons.","date":"2016","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/27502486","citation_count":37,"is_preprint":false},{"pmid":"23562843","id":"PMC_23562843","title":"v-Src causes delocalization of Mklp1, Aurora B, and INCENP from the spindle midzone during cytokinesis failure.","date":"2013","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/23562843","citation_count":37,"is_preprint":false},{"pmid":"9749792","id":"PMC_9749792","title":"Expression of the mitotic motor protein CHO1/MKLP1 in postmitotic neurons.","date":"1998","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/9749792","citation_count":36,"is_preprint":false},{"pmid":"32365332","id":"PMC_32365332","title":"KIF23 activated Wnt/β-catenin signaling pathway through direct interaction with Amer1 in gastric cancer.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/32365332","citation_count":36,"is_preprint":false},{"pmid":"32624708","id":"PMC_32624708","title":"Knockdown of lncRNA PVT1 inhibits prostate cancer progression in vitro and in vivo by the suppression of KIF23 through stimulating miR-15a-5p.","date":"2020","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/32624708","citation_count":31,"is_preprint":false},{"pmid":"34268078","id":"PMC_34268078","title":"KIF23 promotes triple negative breast cancer through activating epithelial-mesenchymal transition.","date":"2021","source":"Gland surgery","url":"https://pubmed.ncbi.nlm.nih.gov/34268078","citation_count":30,"is_preprint":false},{"pmid":"27279560","id":"PMC_27279560","title":"Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma.","date":"2016","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/27279560","citation_count":30,"is_preprint":false},{"pmid":"11842131","id":"PMC_11842131","title":"Zebrafish mitotic kinesin-like protein 1 (Mklp1) functions in embryonic cytokinesis.","date":"2002","source":"Physiological genomics","url":"https://pubmed.ncbi.nlm.nih.gov/11842131","citation_count":29,"is_preprint":false},{"pmid":"17198681","id":"PMC_17198681","title":"The nuclear localization signal of mitotic kinesin-like protein Mklp-1: effect on Mklp-1 function during cytokinesis.","date":"2006","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/17198681","citation_count":26,"is_preprint":false},{"pmid":"28004812","id":"PMC_28004812","title":"p120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28004812","citation_count":23,"is_preprint":false},{"pmid":"33754001","id":"PMC_33754001","title":"Aberrant KIF23 expression is associated with adverse clinical outcome and promotes cellular malignant behavior through the Wnt/β-catenin signaling pathway in Colorectal Cancer.","date":"2021","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/33754001","citation_count":23,"is_preprint":false},{"pmid":"38360598","id":"PMC_38360598","title":"SIRT7 promotes the proliferation and migration of anaplastic thyroid cancer cells by regulating the desuccinylation of KIF23.","date":"2024","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/38360598","citation_count":21,"is_preprint":false},{"pmid":"29066916","id":"PMC_29066916","title":"Mutation analysis and copy number alterations of KIF23 in non-small-cell lung cancer exhibiting KIF23 over-expression.","date":"2017","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/29066916","citation_count":18,"is_preprint":false},{"pmid":"34918847","id":"PMC_34918847","title":"Functional roles of the SHCBP1 and KIF23 interaction in modulating the cell-cycle and cisplatin resistance of head and neck squamous cell carcinoma.","date":"2021","source":"Head & neck","url":"https://pubmed.ncbi.nlm.nih.gov/34918847","citation_count":16,"is_preprint":false},{"pmid":"16418225","id":"PMC_16418225","title":"MKLP1 requires specific domains for its dendritic targeting.","date":"2006","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/16418225","citation_count":15,"is_preprint":false},{"pmid":"37010644","id":"PMC_37010644","title":"KIF23, under regulation by androgen receptor, contributes to nasopharyngeal carcinoma deterioration by activating the Wnt/β-catenin signaling pathway.","date":"2023","source":"Functional & integrative genomics","url":"https://pubmed.ncbi.nlm.nih.gov/37010644","citation_count":15,"is_preprint":false},{"pmid":"34014023","id":"PMC_34014023","title":"MiR-17-5p downregulation alleviates apoptosis and fibrosis in high glucose-induced human mesangial cells through inactivation of Wnt/β-catenin signaling by targeting KIF23.","date":"2021","source":"Environmental toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/34014023","citation_count":14,"is_preprint":false},{"pmid":"38780518","id":"PMC_38780518","title":"KIF23 promotes cervical cancer progression via inhibiting NLRP3-mediated pyroptosis.","date":"2024","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/38780518","citation_count":13,"is_preprint":false},{"pmid":"28539408","id":"PMC_28539408","title":"Temporal regulation of epithelium formation mediated by FoxA, MKLP1, MgcRacGAP, and PAR-6.","date":"2017","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/28539408","citation_count":13,"is_preprint":false},{"pmid":"25658096","id":"PMC_25658096","title":"Binding of Kif23-iso1/CHO1 to 14-3-3 is regulated by sequential phosphorylations at two LATS kinase consensus sites.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25658096","citation_count":13,"is_preprint":false},{"pmid":"35475447","id":"PMC_35475447","title":"Knockdown of circ_0067934 inhibits gastric cancer cell proliferation, migration and invasion via the miR‑1301‑3p/KIF23 axis.","date":"2022","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/35475447","citation_count":12,"is_preprint":false},{"pmid":"36066385","id":"PMC_36066385","title":"KIF23 promotes autophagy-induced imatinib resistance in chronic myeloid leukaemia through activating Wnt/β-catenin pathway.","date":"2022","source":"Clinical and experimental pharmacology & physiology","url":"https://pubmed.ncbi.nlm.nih.gov/36066385","citation_count":12,"is_preprint":false},{"pmid":"33231086","id":"PMC_33231086","title":"Kinesin family member 23 (KIF23) contributes to the progression of bladder cancer cells in vitro and in vivo.","date":"2020","source":"Neoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/33231086","citation_count":12,"is_preprint":false},{"pmid":"18265015","id":"PMC_18265015","title":"Zygotic loss of ZEN-4/MKLP1 results in disruption of epidermal morphogenesis in the C. elegans embryo.","date":"2008","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/18265015","citation_count":12,"is_preprint":false},{"pmid":"10403813","id":"PMC_10403813","title":"Nuclear localization of C-terminal domains of the kinesin-like protein MKLP-1.","date":"1999","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/10403813","citation_count":11,"is_preprint":false},{"pmid":"35457254","id":"PMC_35457254","title":"Inhibition of KIF23 Alleviates IPAH by Targeting Pyroptosis and Proliferation of PASMCs.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35457254","citation_count":11,"is_preprint":false},{"pmid":"36940637","id":"PMC_36940637","title":"FOXM1 augments sorafenib resistance and promotes progression of hepatocellular carcinoma by epigenetically activating KIF23 expression.","date":"2023","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/36940637","citation_count":10,"is_preprint":false},{"pmid":"35002290","id":"PMC_35002290","title":"Systematic Pan-Cancer Analysis of KIF23 and a Prediction Model Based on KIF23 in Clear Cell Renal Cell Carcinoma (ccRCC).","date":"2021","source":"Pharmacogenomics and personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35002290","citation_count":10,"is_preprint":false},{"pmid":"34017355","id":"PMC_34017355","title":"Mutation and Copy Number Alterations Analysis of KIF23 in Glioma.","date":"2021","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34017355","citation_count":9,"is_preprint":false},{"pmid":"39632980","id":"PMC_39632980","title":"Kinesin-like motor protein KIF23 maintains neural stem and progenitor cell pools in the developing cortex.","date":"2024","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/39632980","citation_count":8,"is_preprint":false},{"pmid":"38514510","id":"PMC_38514510","title":"Mechanism of regulation of KIF23 on endometrial cancer cell growth and apoptosis.","date":"2024","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38514510","citation_count":8,"is_preprint":false},{"pmid":"35713434","id":"PMC_35713434","title":"KIF23 is a potential biomarker of diffuse large B cell lymphoma: Analysis based on bioinformatics and immunohistochemistry.","date":"2022","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35713434","citation_count":8,"is_preprint":false},{"pmid":"33159567","id":"PMC_33159567","title":"Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene.","date":"2020","source":"Annals of hematology","url":"https://pubmed.ncbi.nlm.nih.gov/33159567","citation_count":8,"is_preprint":false},{"pmid":"40235270","id":"PMC_40235270","title":"Regulation of KIF23 by miR-107 controls replicative tumor cell fitness in mouse and human hepatocellular carcinoma.","date":"2024","source":"Journal of hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/40235270","citation_count":7,"is_preprint":false},{"pmid":"38336274","id":"PMC_38336274","title":"Identification and validation of KIF23 as a hypoxia-regulated lactate metabolism-related oncogene in uterine corpus endometrial carcinoma.","date":"2024","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38336274","citation_count":7,"is_preprint":false},{"pmid":"34983303","id":"PMC_34983303","title":"DEP domain containing 1B (DEPDC1B) exerts the tumor promoter in hepatocellular carcinoma through activating p53 signaling pathway via kinesin family member 23 (KIF23).","date":"2022","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/34983303","citation_count":7,"is_preprint":false},{"pmid":"36197340","id":"PMC_36197340","title":"Membrane compartmentalization of Ect2/Cyk4/Mklp1 and NuMA/dynein regulates cleavage furrow formation.","date":"2022","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/36197340","citation_count":6,"is_preprint":false},{"pmid":"38569671","id":"PMC_38569671","title":"Knockdown of KIF23 alleviates the progression of asthma by inhibiting pyroptosis.","date":"2024","source":"BMJ open respiratory research","url":"https://pubmed.ncbi.nlm.nih.gov/38569671","citation_count":6,"is_preprint":false},{"pmid":"40639436","id":"PMC_40639436","title":"KIF23 inhibition protects against perioperative neurocognitive disorders by hindering ROS/caspase-3/GSDME-mediated pyroptosis.","date":"2025","source":"Experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/40639436","citation_count":5,"is_preprint":false},{"pmid":"32818800","id":"PMC_32818800","title":"Differential tissue specific expression of Kif23 alternative transcripts in mice with the human mutation causing congenital dyserythropoietic anemia type III.","date":"2020","source":"Blood cells, molecules & diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32818800","citation_count":5,"is_preprint":false},{"pmid":"33204722","id":"PMC_33204722","title":"Revealing PAK2's Function in the Cell Division through MKLP1's Interactome.","date":"2020","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/33204722","citation_count":5,"is_preprint":false},{"pmid":"37198502","id":"PMC_37198502","title":"KCNQ1OT1 promotes retinoblastoma progression by targeting miR-339-3p that suppresses KIF23.","date":"2023","source":"International ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/37198502","citation_count":3,"is_preprint":false},{"pmid":"31057046","id":"PMC_31057046","title":"Inhibition of neddylation induces mitotic defects and alters MKLP1 accumulation at the midbody during cytokinesis.","date":"2019","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/31057046","citation_count":3,"is_preprint":false},{"pmid":"9799428","id":"PMC_9799428","title":"Sequence and expression of DmMKLP1, a homolog of the human MKLP1 kinesin-like protein from Drosophila melanogaster.","date":"1998","source":"Development genes and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/9799428","citation_count":3,"is_preprint":false},{"pmid":"41078122","id":"PMC_41078122","title":"Kif23 Promotes Myocardial Fibrosis by Suppressing Ces1d-Dependent Lipid Metabolism.","date":"2025","source":"Hypertension (Dallas, Tex. : 1979)","url":"https://pubmed.ncbi.nlm.nih.gov/41078122","citation_count":2,"is_preprint":false},{"pmid":"39867833","id":"PMC_39867833","title":"Cancer-associated fibroblast-derived exosomal FAM83F regulates KIF23 expression to promote the malignant progression and reduce radiosensitivity in non-small cell lung cancer.","date":"2025","source":"Cytotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/39867833","citation_count":2,"is_preprint":false},{"pmid":"40983152","id":"PMC_40983152","title":"ETV5 transcriptionally inhibits KIF23 to repress pyroptosis in aged mice with perioperative neurocognitive disorders.","date":"2025","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/40983152","citation_count":1,"is_preprint":false},{"pmid":"39725112","id":"PMC_39725112","title":"Molecular structure of polysaccharide mediated autophagy markers KIF23 and PRC1 proteins and their regulatory role in triple negative cancer through the p53 signaling pathway.","date":"2024","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39725112","citation_count":1,"is_preprint":false},{"pmid":"40902449","id":"PMC_40902449","title":"Assessment of anti-cancer activity of cyclovirobuxine D in nasopharyngeal carcinoma cells: Involvement of KIF23-mediated Akt/mTOR pathway.","date":"2025","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/40902449","citation_count":1,"is_preprint":false},{"pmid":"42178466","id":"PMC_42178466","title":"KIF23 in disease pathogenesis and its therapeutic and diagnostic potential.","date":"2026","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/42178466","citation_count":0,"is_preprint":false},{"pmid":"41940421","id":"PMC_41940421","title":"Targeting KIF23 inhibits cell proliferation and primary chemoresistance in cervical cancer by inactivating the MYH9/MCM2/PCNA pathway.","date":"2026","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41940421","citation_count":0,"is_preprint":false},{"pmid":"41373021","id":"PMC_41373021","title":"A core stemness-associated module reveals PLK1, NUF2, KIF23, CDCA8, TOP2A, CENPF, AURKA, and ASPM as key genes in rectal cancer.","date":"2025","source":"European journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/41373021","citation_count":0,"is_preprint":false},{"pmid":"41138746","id":"PMC_41138746","title":"KIF23 silencing suppresses papillary thyroid carcinoma metastasis by regulating mitophagy via Wnt/β-catenin pathway.","date":"2025","source":"Endocrine connections","url":"https://pubmed.ncbi.nlm.nih.gov/41138746","citation_count":0,"is_preprint":false},{"pmid":"41675939","id":"PMC_41675939","title":"KIF23 Overexpression Promotes Cell Viability, Migration, and Invasion via the Wnt/β-Catenin Signaling Pathway in Anaplastic Thyroid Carcinoma.","date":"2026","source":"International journal of endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/41675939","citation_count":0,"is_preprint":false},{"pmid":"39155879","id":"PMC_39155879","title":"[Corrigendum] Knockdown of circ_0067934 inhibits gastric cancer cell proliferation, migration and invasion via the miR‑1301‑3p/KIF23 axis.","date":"2024","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/39155879","citation_count":0,"is_preprint":false},{"pmid":"40726601","id":"PMC_40726601","title":"RETRACTION: KIF23 Promotes Gastric Cancer by Stimulating Cell Proliferation.","date":"2025","source":"Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/40726601","citation_count":0,"is_preprint":false},{"pmid":"40927401","id":"PMC_40927401","title":"Congenital Dyserythropoietic Anemia Type III Associated With a Novel KIF23 Variant (c.2132A>G; p.Gln711Arg): A Case Report.","date":"2025","source":"Clinical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/40927401","citation_count":0,"is_preprint":false},{"pmid":"41874817","id":"PMC_41874817","title":"NCBP2 Regulates PGAM5-Mediated Mitophagy Via KIF23 Alternative Splicing To Promote Cervical Cancer ProgressionRun Title: NCBP2 Promotes Cervical Cancer Via Mitophagy.","date":"2026","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/41874817","citation_count":0,"is_preprint":false},{"pmid":"42154117","id":"PMC_42154117","title":"DLX6-AS1 promotes the progression of Wilms tumor by sponging miR-195-5p to upregulate KIF23 in Wilms tumor cells.","date":"2026","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/42154117","citation_count":0,"is_preprint":false},{"pmid":"38550036","id":"PMC_38550036","title":"Retracted: Revealing PAK2's Function in the Cell Division through MKLP1's Interactome.","date":"2024","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/38550036","citation_count":0,"is_preprint":false},{"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},{"pmid":null,"id":"bio_10.1101_2025.02.19.639158","title":"Examination of germline and somatic intercellular bridges in  <i>Hydra vulgaris</i>  reveals insights into the evolutionarily conserved mechanism of intercellular bridge formation","date":"2025-02-20","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.19.639158","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.09.18.613761","title":"Centralspindlin promotes  <i>C. elegans</i>  anchor cell specification, vulva induction and morphogenesis","date":"2024-09-19","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.18.613761","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.08.21.609070","title":"Identification and Functional Characterization of Up-Regulated Hub Genes in Adenocarcinoma Across Multiple Organ Sites","date":"2024-08-22","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.21.609070","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.08.16.607330","title":"Phylogenetic analysis of Centralspindlin and Ect2 provides mechanistic insights into the emergence of Metazoa and multicellularity","date":"2024-08-17","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.16.607330","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":43814,"output_tokens":8854,"usd":0.132126,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":18580,"output_tokens":4610,"usd":0.104075,"stage2_stop_reason":"end_turn"},"total_usd":0.236201,"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\": 1995,\n      \"finding\": \"PLK (Plk1) physically interacts with CHO1/MKLP-1 in vivo, co-localizes with it at the midbody during telophase/cytokinesis, and phosphorylates CHO1/MKLP-1 in vitro via Plk-associated kinase activity.\",\n      \"method\": \"Co-immunoprecipitation, co-localization by immunofluorescence, in vitro kinase assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and in vitro kinase assay in single lab; later confirmed by Liu et al. 2004\",\n      \"pmids\": [\"8524282\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Plk1 binds CHO1/MKLP-1 through its Polo-box domain, while the stalk domain of CHO1/MKLP-1 mediates binding to Plk1. Ser904 and Ser905 are the two major Plk1 phosphorylation sites on CHO1/MKLP-1. Depletion of CHO1/MKLP-1 mislocalizes Plk1 during late mitosis. A non-phosphorylatable CHO1 mutant causes cytokinesis defects, and rescue of CHO1-depletion-induced multinucleation requires the phosphorylatable form.\",\n      \"method\": \"Transient transfection, domain-deletion analysis, vector-based RNAi, site-directed mutagenesis, rescue experiments\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (domain mapping, mutagenesis of phosphosites, RNAi depletion, rescue) in single lab; replicates and extends earlier Plk1/MKLP1 interaction finding\",\n      \"pmids\": [\"15199097\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Aurora B phosphorylates ZEN-4/MKLP1 in vitro and in vivo on conserved C-terminal serine residues. A non-phosphorylatable ZEN-4 mutant localizes properly but fails to support completion of cytokinesis in C. elegans embryos. Inhibition of aurora B in late anaphase in mammalian cells attenuates MKLP1 phosphorylation and causes cytokinesis defects without disrupting the central spindle.\",\n      \"method\": \"In vitro kinase assay, in vivo phosphorylation (C. elegans and human cells), phospho-mutant analysis, aurora kinase inhibitor treatment\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro kinase assay plus in vivo validation plus phospho-mutant functional analysis across two species\",\n      \"pmids\": [\"15854913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"INCENP is required for recruiting MKLP1 to the spindle midzone/midbody. Depletion of MKLP1 by siRNA does not cause chromosome segregation or midzone formation defects, but abrogates midbody formation and completion of cytokinesis. INCENP-mediated recruitment of MKLP1 to the midzone/midbody is a crucial step for midbody formation.\",\n      \"method\": \"RNAi/siRNA knockdown, immunofluorescence, 3D live-cell imaging reconstruction\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal imaging methods plus functional RNAi depletion in single lab\",\n      \"pmids\": [\"15796717\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Centralspindlin is a heterotetrameric complex consisting of two CYK-4/MgcRacGAP homodimers and two ZEN-4/MKLP1 homodimers (each subunit dimerizing via parallel coiled coils) assembled through two low-affinity interactions. The assembled centralspindlin complex, but not individual subunits alone, is sufficient to bundle microtubules in vitro.\",\n      \"method\": \"Biochemical reconstitution, in vitro microtubule bundling assay, genetic epistasis (suppressor screen with second-site mutations), co-immunoprecipitation\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution in vitro plus mutagenesis plus genetic suppressor analysis; replicated across species contexts\",\n      \"pmids\": [\"17942600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Activated (GTP-bound) Arf proteins bind directly to an 88-amino-acid domain in the C-terminal tail of MKLP1. This interaction is GTP-dependent and maps to the switch I and switch II regions of Arf3. All human Arf isoforms interact with the MKLP1 C-terminal domain.\",\n      \"method\": \"Yeast two-hybrid screen, GST pulldown assay, deletion mapping, Arf3 point-mutation screen\",\n      \"journal\": \"Cell motility and the cytoskeleton\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus GST pulldown plus mutagenesis in single lab\",\n      \"pmids\": [\"10506747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Arf6 directly interacts with MKLP1 to form a 2:2 heterotetramer. Crystal structure reveals an extended β-sheet spanning the entire heterotetramer, suitable for interaction with concave membrane surfaces at the cleavage furrow. Arf6 first accumulates around the cleavage furrow, then is recruited to the Flemming body via MKLP1. Structure-based mutagenesis and siRNA knockdown show complex formation is required for completion of cytokinesis.\",\n      \"method\": \"Crystal structure determination, structure-based mutagenesis, siRNA knockdown, live-cell imaging\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus functional mutagenesis plus siRNA validation in single rigorous study\",\n      \"pmids\": [\"22522702\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TRAF6 mediates K63-linked ubiquitination of the midbody ring-localized protein KIF23/MKLP1. This ubiquitination is important for recognition by ubiquitin-binding autophagy receptors SQSTM1/p62 and NBR1 (together with WDFY3/ALFY) and subsequent degradation of midbody ring derivatives by selective autophagy.\",\n      \"method\": \"siRNA depletion, ubiquitination assay, co-immunoprecipitation, immunofluorescence\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus ubiquitination assay plus functional depletion in single lab\",\n      \"pmids\": [\"24128730\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"A missense mutation c.2747C>G (p.P916R) in KIF23 causes autosomal dominant congenital dyserythropoietic anemia type III (CDA III). RNAi knockdown and rescue experiments in HeLa cells demonstrated that the p.P916R mutation causes cytokinesis failure, consistent with the large multinucleated erythroblasts observed in CDA III patients.\",\n      \"method\": \"Next-generation resequencing, haplotype analysis, RNAi knockdown and rescue in HeLa cells, functional cytokinesis assay\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic identification plus functional rescue experiment; segregation confirmed in two independent families\",\n      \"pmids\": [\"23570799\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"CHO1/MKLP1 is associated with microtubules in podocytes and is required for establishing nonuniform (mixed) microtubule polarity. Antisense oligonucleotide-mediated depletion of CHO1/MKLP1 in differentiating podocytes abolished process formation and the nonuniform polarity of microtubules, demonstrating that MKLP1-dependent microtubule polarity is necessary for process formation.\",\n      \"method\": \"Antisense oligonucleotide treatment, hook-decoration of microtubules (polarity assay), taxol/nocodazole recovery experiments, immunolocalization\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — antisense depletion with specific phenotypic readout plus MT polarity assay in single lab\",\n      \"pmids\": [\"9864367\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"CHO1/MKLP1 is expressed in postmitotic neurons including hippocampal, cortical, and cerebellar neurons. Expression peaks prior to dendritic development and decreases afterward. Dorsal root ganglion neurons that form axons but not dendrites express significantly lower levels, consistent with a role for MKLP1 in establishing the nonuniform microtubule polarity characteristic of dendrites.\",\n      \"method\": \"In situ hybridization (rodent brain sections), mRNA expression analysis in cultured neurons\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — expression/localization only, no direct functional manipulation in this paper\",\n      \"pmids\": [\"9749792\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"ZEN-4/MKLP1 functions postmitotically to establish foregut epithelium polarity in C. elegans. zen-4 mutants express polarity markers but fail to target PAR-3/Bazooka, PKC-3/aPKC, HMR-1/cadherin, and AJM-1 to correct cortical domains, and show disorganized microtubules and actin, indicating MKLP1 regulates an early step in epithelial polarization.\",\n      \"method\": \"Genetic mutant analysis, immunofluorescence of polarity markers, confocal microscopy in C. elegans\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with multiple defined molecular readouts in C. elegans model\",\n      \"pmids\": [\"15182666\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Two nuclear localization signals (NLSs) in the tail domain of Mklp-1 were mapped to residues 899SRKRRSST906 and 949KRKKP953. Ectopic expression of an NLS-deleted mutant causes cell cycle arrest at cytokinesis. Phosphomimetic mutation of two serine residues in the first NLS (S→D) attenuates nuclear localization, suggesting NLS activity is regulated by phosphorylation.\",\n      \"method\": \"Deletion/mutation mapping, ectopic expression, fluorescence microscopy, cell cycle analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mapping plus functional mutant analysis with specific cytokinesis arrest readout in single lab\",\n      \"pmids\": [\"17198681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"The C-terminal domain of MKLP-1 contains at least one nuclear localization sequence; C-terminal constructs fused to GFP localize to the nucleus in HeLa cells and remain tightly associated with the nucleus following detergent and salt extraction, indicating stable interaction with a nuclear component.\",\n      \"method\": \"GFP-fusion expression in HeLa cells, subcellular fractionation, fluorescence microscopy\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization method, no functional manipulation\",\n      \"pmids\": [\"10403813\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The motor domain and tail domain of MKLP1 are both required for dendritic targeting in hippocampal neurons. Deletion of the motor domain prevents dendritic distribution; deletion of the tail domain causes axonal mis-targeting; deletion of the stalk domain does not affect dendritic specificity.\",\n      \"method\": \"GFP-tagged domain deletion constructs expressed in primary hippocampal neurons, fluorescence microscopy\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic domain-deletion mapping with clear localization readouts in primary neurons\",\n      \"pmids\": [\"16418225\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"p53 transcriptionally represses KIF23 mRNA and protein expression. This repression is mediated through the CDK inhibitor p21(WAF1/CIP1) and requires a cell cycle genes homology region (CHR) element in the KIF23 promoter. Cell cycle- and p53-dependent regulation of KIF23 involves differential binding of DREAM and MMB complexes to the CHR element.\",\n      \"method\": \"Promoter-reporter assays, chromatin immunoprecipitation (DREAM/MMB binding to CHR), siRNA knockdown of p21, RT-PCR and western blot\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (ChIP, reporter assays, siRNA) in single lab\",\n      \"pmids\": [\"23650552\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CUX1 and E2F1 cooperatively regulate KIF23/MKLP1 transcription at S-phase entry. Both transcription factors bind the MKLP1 promoter (demonstrated by ChIP) upon S-phase entry via CHR elements and E2F binding elements. Overexpression of either E2F1 or CUX1 increases endogenous MKLP1 levels; siRNA knockdown or dominant-negative E2F1 reduces expression.\",\n      \"method\": \"Chromatin immunoprecipitation, promoter-luciferase reporter assays, siRNA knockdown, overexpression\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus reporter assays plus functional knockdown/overexpression in single lab\",\n      \"pmids\": [\"19015243\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The two LATS/NDR kinase consensus sites (S716 and S814) in the long Kif23/CHO1 isoform are phosphorylated by NDR and LATS kinases in vitro. LATS1/2 contribute to S814 phosphorylation in vivo. Phosphorylation of the upstream S716 site is required for efficient phosphorylation at S814, revealing sequential phosphorylation. S814 phosphorylation constitutes a 14-3-3 binding site involved in Kif23 clustering during cytokinesis, and this modification is absent in post-abscission midbodies.\",\n      \"method\": \"In vitro kinase assay, site-directed mutagenesis, in vivo phosphorylation assay, 14-3-3 binding assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase reconstitution plus mutagenesis plus in vivo validation; single lab\",\n      \"pmids\": [\"25658096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In Drosophila motoneurons, the Toll-6 receptor–dSARM–FoxO signaling pathway represses expression of Pavarotti/MKLP1 (the Drosophila ortholog). Elevated Pavarotti/MKLP1 attenuates microtubule dynamics. Toll-6-FoxO signaling promotes MT dynamics by limiting Pav-KLP expression, and this pathway is essential for axon transport and activity-dependent structural plasticity in motoneurons.\",\n      \"method\": \"Genetic epistasis (Drosophila pathway mutants), genetic suppression, in vivo imaging of MT dynamics, overexpression of Pav-KLP\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis plus in vivo imaging plus rescue experiment in Drosophila model\",\n      \"pmids\": [\"27502486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"v-Src induces cytokinesis failure by delocalizing Mklp1 from the spindle midzone. Aurora B, which regulates Mklp1 localization, and Mklp2 (responsible for Aurora B relocation from chromosomes to midzone) are also delocalized from the spindle midzone upon v-Src expression, placing Mklp1 downstream of the v-Src-Aurora B-Mklp2 axis.\",\n      \"method\": \"Inducible v-Src expression, flow cytometry, time-lapse microscopy, immunofluorescence localization\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — inducible expression system with multiple localization and cell division readouts in single lab\",\n      \"pmids\": [\"23562843\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"p120-catenin (p120) binds directly to MKLP1 and to RhoA at the cleavage furrow during anaphase. The N-terminal coiled-coil domain of p120 isoform 1A is required for MKLP1 binding. p120 spatially controls RhoA GTPase cycling through concomitant binding to RhoA and MKLP1, and loss of p120 leads to multinucleation.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence (cleavage furrow enrichment), domain deletion analysis, siRNA knockdown\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP plus domain mapping plus functional knockdown in single lab\",\n      \"pmids\": [\"28004812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The tail domain of MKLP1 exhibits an autoinhibitory effect on its motor activity. Overexpression of the tail domain alone blocks cytokinesis and causes bi-/multinucleation. PAK2 (p21-activated kinase 2) binds to the MKLP1 tail domain (confirmed by GST pulldown, LC-MS/MS, co-IP, and FRET). PAK2 knockdown by siRNA mislocalizes MKLP1 from the midbody and impedes cytokinesis, suggesting PAK2 relieves MKLP1 autoinhibition to promote cytokinesis.\",\n      \"method\": \"GST pulldown followed by LC-MS/MS, co-immunoprecipitation, FRET, siRNA knockdown, overexpression\",\n      \"journal\": \"BioMed research international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — paper subsequently retracted (PMID 38550036); findings are unreliable\",\n      \"pmids\": [\"33204722\", \"38550036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The centralspindlin complex (Cyk4/Mklp1) and its interacting partner RhoGEF Ect2 are required for exclusion of NuMA/dynein/dynactin from the equatorial cell membrane during anaphase. The equatorial membrane enrichment of the Ect2/Cyk4/Mklp1 complex is essential for NuMA/dynein/dynactin exclusion and proper spindle elongation, linking centralspindlin to coordination of spindle elongation with cleavage furrow formation.\",\n      \"method\": \"siRNA depletion, live-cell imaging (membrane compartmentalization), immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple depletions with quantitative imaging readouts in single lab\",\n      \"pmids\": [\"36197340\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF23 directly interacts with APC membrane recruitment 1 (Amer1) protein. This interaction displaces Amer1 from the membrane/cytoplasm to the nucleus and blocks Amer1's association with APC, thereby attenuating Amer1's negative regulation of Wnt/β-catenin signaling and promoting nuclear β-catenin accumulation.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence (subcellular localization of Amer1), functional rescue experiments, western blot\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP demonstrating direct binding plus localization shift plus functional consequences in single lab\",\n      \"pmids\": [\"32365332\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SIRT7 interacts with KIF23 and inhibits succinylation of KIF23 at lysine K537. SIRT7-mediated desuccinylation enhances the protein stability of KIF23, and SIRT7 overexpression promotes anaplastic thyroid cancer cell viability and migration partly via KIF23.\",\n      \"method\": \"Co-immunoprecipitation, western blot for succinylation, overexpression/silencing in HEK-293T and ATC cells, cell viability/migration assays\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus site-specific PTM assay plus functional rescue in single lab\",\n      \"pmids\": [\"38360598\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FOXM1 epigenetically activates KIF23 expression by increasing RNA polymerase II and histone H3K27 acetylation at the KIF23 promoter. Downregulation of FOXM1 reduces KIF23 levels and alleviates sorafenib resistance in hepatocellular carcinoma cells.\",\n      \"method\": \"ChIP for RNA pol II and H3K27ac at KIF23 promoter, siRNA knockdown, western blot, drug resistance assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP plus functional knockdown with defined epigenetic mechanism in single lab\",\n      \"pmids\": [\"36940637\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIF23 knockdown in embryonic mouse cortex causes precocious neurogenesis and neuronal apoptosis, attributed to accelerated cell cycle exit from disrupted mitotic spindle orientation and impaired cytokinesis. KIF23 depletion also perturbs apical surface structure of neural stem and progenitor cells by affecting localization of apical junction proteins. Wild-type human KIF23 rescues these phenotypes, but a microcephaly-associated KIF23 variant does not.\",\n      \"method\": \"In utero electroporation knockdown in mice, immunofluorescence, live imaging, rescue with wild-type vs. variant human KIF23\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo loss-of-function with multiple cellular phenotype readouts plus allele-specific rescue experiment\",\n      \"pmids\": [\"39632980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Zebrafish Mklp1 redistributes from spindle microtubules at metaphase to the spindle midzone during anaphase and concentrates in the midbody during telophase/cytokinesis. Nuclear targeting is conferred by two basic motifs in the COOH terminus. Dominant-negative Mklp1 variants in one- or two-cell zebrafish embryos cause failure to complete cytokinesis, resulting in multinucleated blastomeres.\",\n      \"method\": \"GFP-tagging and live imaging in zebrafish embryos, dominant-negative mRNA injection, fractionation\",\n      \"journal\": \"Physiological genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging plus dominant-negative functional experiment in vertebrate model\",\n      \"pmids\": [\"11842131\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NAT10-mediated ac4C modification of KIF23 mRNA at its 3'UTR region stabilizes KIF23 mRNA and elevates KIF23 protein levels, which in turn activates the Wnt/β-catenin pathway to promote colorectal cancer progression. GSK-3β negatively regulates NAT10 forming a feedback loop.\",\n      \"method\": \"RIP-seq, acRIP-seq, RNA immunoprecipitation, luciferase reporter assay, siRNA knockdown, xenograft models\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple RNA biochemistry methods plus functional in vivo validation in single lab\",\n      \"pmids\": [\"36522719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Neddylation inhibition by MLN4924 causes premature accumulation of MKLP1 at the cleavage furrow during mitosis, which is associated with increased abscission delay and failure. NEDD8 and CSN subunits localize to the midbody and cleavage furrow, indicating neddylation/deneddylation regulation at the midbody controls MKLP1 timing.\",\n      \"method\": \"MLN4924 drug treatment in synchronized cells, fixed and live-cell microscopy, immunofluorescence\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — pharmacological inhibition with localization readout, no direct mechanistic link established between neddylation and MKLP1\",\n      \"pmids\": [\"31057046\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The C-terminal domain of KIF23 directly binds to the myosin tail domain of MYH9. This interaction stabilizes MYH9 by recruiting deubiquitinase USP7, which removes K48-linked ubiquitin chains from MYH9. Elevated MYH9 then promotes recruitment of USP15 to deubiquitinate MCM2 at K469, preventing MCM2 degradation and enabling MCM2-PCNA interaction to promote cell cycle progression and cisplatin resistance in cervical cancer.\",\n      \"method\": \"Co-immunoprecipitation, protein half-life assays, ubiquitination assays, CRISPR/Cas9 knockout, site-directed mutagenesis\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus ubiquitination assays plus site-specific mutagenesis in single lab\",\n      \"pmids\": [\"41940421\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In cardiac fibroblasts, Kif23 promotes fibrosis by activating the RhoA/ROCK1 signaling axis, which suppresses Ces1d-mediated fatty acid β-oxidation, leading to lipid accumulation and myofibroblast transdifferentiation. Kif23 knockdown in vivo (post-MI mouse model) improved cardiac function and attenuated fibrosis.\",\n      \"method\": \"Proteomic profiling of knockdown vs. overexpression fibroblasts, adeno-associated virus shRNA knockdown in vivo, western blot, lipid droplet analysis, echocardiography\",\n      \"journal\": \"Hypertension\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomics plus in vivo loss-of-function with defined downstream effector (Ces1d) in single lab\",\n      \"pmids\": [\"41078122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ETV5 transcription factor directly binds to the KIF23 promoter region (within 1–700 bp upstream of the transcription start site) and represses KIF23 transcription. ETV5 overexpression suppresses caspase-3/GSDME-mediated pyroptosis and cognitive impairment in a perioperative neurocognitive disorder model, and this protective effect is neutralized by KIF23 overexpression.\",\n      \"method\": \"Chromatin immunoprecipitation (ETV5 binding to KIF23 promoter), AAV9-mediated overexpression/knockdown in mice, western blot, cognitive behavior assays\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP demonstrating direct promoter binding plus in vivo functional rescue/reversal in single lab\",\n      \"pmids\": [\"40983152\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SHCBP1 interacts with KIF23 via its Nesd homology domain (NHD) and this interaction is important for KIF23's nuclear localization. SHCBP1 positively modulates KIF23 expression. KIF23 knockdown abrogates cisplatin resistance induced by SHCBP1 overexpression, placing KIF23 downstream of SHCBP1 in modulating cisplatin resistance.\",\n      \"method\": \"Co-immunoprecipitation (domain mapping), siRNA knockdown, overexpression, drug sensitivity assays\",\n      \"journal\": \"Head & neck\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP plus functional knockdown without in vitro reconstitution\",\n      \"pmids\": [\"34918847\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CDK1 and Aurora B phosphorylate two serine residues (S440 and S699) on Citron kinase (CIT-K), and phosphorylation at either residue reduces the ability of CIT-K to interact with its midbody partners including KIF23/MKLP1, thereby regulating midbody formation and stability.\",\n      \"method\": \"In vitro kinase assay, phospho-mutant analysis, co-immunoprecipitation, live-cell imaging\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — rigorous preprint with in vitro assay and mutagenesis but not yet peer-reviewed; KIF23 is one of multiple partners, not the primary subject\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"KIF23/MKLP1 is a kinesin-6 motor protein that forms the centralspindlin heterotetrameric complex with CYK-4/MgcRacGAP; this complex bundles antiparallel midzone microtubules during anaphase, is recruited to the midbody via INCENP, and drives cytokinesis completion through regulation by Aurora B phosphorylation (on conserved C-terminal serines), Plk1 phosphorylation (on Ser904/905 via a Polo-box–stalk domain interaction), LATS/NDR-mediated sequential phosphorylation (S716→S814) creating a 14-3-3 binding site, and Arf6 binding to its C-terminal tail; TRAF6-mediated ubiquitination of MKLP1 at the post-abscission midbody ring marks it for selective autophagy; in neurons, MKLP1 establishes nonuniform microtubule polarity in dendrites via its motor and tail domains; loss-of-function mutations cause cytokinesis failure manifesting as congenital dyserythropoietic anemia type III and microcephaly; and in cancer contexts KIF23 activates oncogenic signaling (Wnt/β-catenin, PI3K/AKT, RhoA/ROCK1) through direct protein interactions (Amer1, MYH9) and is transcriptionally regulated by p53/DREAM, MMB/FOXM1, and epigenetic mechanisms.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF23/MKLP1 is a kinesin-6 motor protein that drives the completion of cytokinesis by organizing the antiparallel microtubules of the anaphase central spindle and midbody [#4]. It assembles into the heterotetrameric centralspindlin complex with CYK-4/MgcRacGAP, and only the intact complex—not the individual subunits—bundles microtubules in vitro [#4]; this complex also coordinates spindle elongation with furrow ingression by excluding NuMA/dynein/dynactin from the equatorial membrane together with the RhoGEF Ect2 [#22]. MKLP1 is recruited to the spindle midzone and midbody via INCENP, a step required for midbody formation but not for chromosome segregation [#3]. Its activity is gated by a layered phosphoregulatory program: Aurora B phosphorylates conserved C-terminal serines to license cytokinesis completion [#2], Plk1 binds through its Polo-box to the MKLP1 stalk and phosphorylates Ser904/Ser905, with MKLP1 in turn governing Plk1 localization in late mitosis [#0, #1], and sequential LATS/NDR phosphorylation at S716 then S814 creates a 14-3-3 binding site controlling MKLP1 clustering [#17]. The C-terminal tail mediates additional regulatory contacts, binding GTP-loaded Arf6 to form a membrane-apposed 2:2 heterotetramer required for abscission [#5, #6] and p120-catenin to spatially control RhoA cycling at the furrow [#20]; after abscission, TRAF6-mediated K63 ubiquitination marks the midbody-ring pool for clearance by selective autophagy [#7]. Beyond division, MKLP1 acts postmitotically to establish the nonuniform microtubule polarity of dendrites through its motor and tail domains [#14] and to organize epithelial polarity [#11], and it is required in the developing cortex for proper spindle orientation and progenitor cytokinesis [#26]. A missense KIF23 mutation (p.P916R) causes autosomal dominant congenital dyserythropoietic anemia type III through cytokinesis failure [#8], and a microcephaly-associated variant fails to rescue cortical neurogenesis defects [#26]. In cancer, KIF23 is induced by FOXM1 and CUX1/E2F1 and repressed by the p53/p21/DREAM axis [#15, #16, #25], and it promotes oncogenic Wnt/β-catenin signaling by sequestering Amer1 and stabilizing MYH9 to drive proliferation and drug resistance [#23, #30].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Established that MKLP1 is a physical and enzymatic target of a mitotic kinase, opening the question of how its cytokinetic function is regulated.\",\n      \"evidence\": \"Co-IP, co-localization, and in vitro kinase assay with Plk1 in mammalian cells\",\n      \"pmids\": [\"8524282\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphosites not mapped\", \"Functional consequence of phosphorylation undefined\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Showed MKLP1 has a postmitotic function in establishing mixed microtubule polarity, separating its role from cell division.\",\n      \"evidence\": \"Antisense depletion plus hook-decoration MT polarity assay in podocytes; expression profiling in neurons\",\n      \"pmids\": [\"9864367\", \"9749792\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of polarity establishment unresolved\", \"Neuronal expression data correlative only\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identified the C-terminal tail as a regulatory/interaction module by mapping Arf binding and nuclear localization activity.\",\n      \"evidence\": \"Yeast two-hybrid, GST pulldown, Arf3 mutagenesis; GFP-fusion fractionation in HeLa\",\n      \"pmids\": [\"10506747\", \"10403813\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological role of Arf binding not established here\", \"Nuclear component bound by NLS unidentified\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Defined the Plk1-MKLP1 interaction at domain and residue resolution and showed reciprocal dependence for cytokinesis, establishing MKLP1 as both Plk1 substrate and localization scaffold.\",\n      \"evidence\": \"Domain mapping, phosphosite mutagenesis (Ser904/905), RNAi depletion and rescue; C. elegans epithelial polarity genetics\",\n      \"pmids\": [\"15199097\", \"15182666\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How Ser904/905 phosphorylation alters molecular activity unclear\", \"Link between Plk1 mislocalization and abscission failure mechanistic detail missing\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified Aurora B as a cytokinesis-licensing kinase for MKLP1 and INCENP as its midzone/midbody recruitment factor, defining the recruitment-and-activation logic.\",\n      \"evidence\": \"In vitro kinase assay plus phospho-mutant analysis in C. elegans and human cells; RNAi plus 3D imaging for INCENP dependence\",\n      \"pmids\": [\"15854913\", \"15796717\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise C-terminal serines not all enumerated\", \"How phosphorylation drives abscission completion not mechanistically resolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Established the heterotetrameric architecture of centralspindlin and showed that complex assembly, not isolated subunits, confers microtubule-bundling, defining the minimal functional unit.\",\n      \"evidence\": \"Biochemical reconstitution, in vitro bundling assay, genetic suppressor screen, co-IP\",\n      \"pmids\": [\"17942600\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of bundling not determined\", \"Regulation of assembly in cells incomplete\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Provided a structural mechanism for membrane engagement at the cleavage furrow through the MKLP1-Arf6 heterotetramer.\",\n      \"evidence\": \"Crystal structure, structure-based mutagenesis, siRNA, live imaging\",\n      \"pmids\": [\"22522702\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Coordination of Arf6 binding with motor activity unresolved\", \"Upstream control of Arf6 GTP loading at furrow undefined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Connected MKLP1 to human disease and post-abscission turnover, showing a point mutation causes CDA III via cytokinesis failure and that TRAF6 ubiquitination targets the midbody ring for autophagy.\",\n      \"evidence\": \"Genetic identification plus RNAi rescue in HeLa (p.P916R); ubiquitination assay, co-IP, autophagy receptor analysis; p53/p21/DREAM transcriptional regulation; v-Src delocalization\",\n      \"pmids\": [\"23570799\", \"24128730\", \"23650552\", \"23562843\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How p.P916R perturbs molecular function unclear\", \"Trigger for midbody-ring ubiquitination in normal cells undefined\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed a sequential LATS/NDR phosphorylation switch that creates a 14-3-3 binding site controlling MKLP1 clustering during cytokinesis.\",\n      \"evidence\": \"In vitro kinase assay, S716/S814 mutagenesis, in vivo phosphorylation, 14-3-3 binding assay\",\n      \"pmids\": [\"25658096\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How clustering relates to bundling/abscission unresolved\", \"Isoform-specificity of long CHO1 form in vivo unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrated MKLP1 partners with p120-catenin to spatially control RhoA cycling at the furrow and is transcriptionally limited in neurons by Toll-6/dSARM/FoxO signaling.\",\n      \"evidence\": \"Reciprocal co-IP, domain mapping, siRNA (p120); Drosophila genetic epistasis and MT-dynamics imaging (Toll-6/FoxO)\",\n      \"pmids\": [\"28004812\", \"27502486\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which MKLP1 modulates RhoA GAP/GEF activity unclear\", \"Direct vs. indirect transcriptional control of MKLP1 by FoxO undefined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended centralspindlin function to membrane compartmentalization, showing it excludes NuMA/dynein/dynactin from the equatorial membrane to coordinate spindle elongation with furrowing; cancer studies linked KIF23 mRNA stability to oncogenic Wnt signaling.\",\n      \"evidence\": \"siRNA depletion plus live imaging (membrane exclusion); RIP-seq/acRIP-seq and xenografts for NAT10-mediated ac4C modification\",\n      \"pmids\": [\"36197340\", \"36522719\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular basis of NuMA exclusion unresolved\", \"Relationship between cytokinetic and oncogenic functions unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established a developmental cortical requirement for KIF23 with allele-specific causality for microcephaly, and identified PTM-mediated stability control via SIRT7 desuccinylation.\",\n      \"evidence\": \"In utero electroporation knockdown plus rescue with WT vs. microcephaly variant; co-IP and site-specific succinylation assays (SIRT7/K537)\",\n      \"pmids\": [\"39632980\", \"38360598\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether cortical phenotype reflects cytokinesis vs. spindle orientation defects not fully separated\", \"Generality of K537 succinylation across tissues unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Expanded KIF23 oncogenic and fibrotic signaling, linking it to MYH9 stabilization, RhoA/ROCK1-driven fibrosis, and transcriptional repression by ETV5.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, CRISPR knockout (MYH9/USP7/MCM2); proteomics and in vivo shRNA (cardiac fibrosis); ChIP and AAV9 rescue (ETV5)\",\n      \"pmids\": [\"41940421\", \"41078122\", \"40983152\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether motor activity is required for signaling functions unclear\", \"Direct vs. scaffold roles in deubiquitinase recruitment not separated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the layered phosphorylation, ubiquitination, and PTM inputs are integrated to time MKLP1 motor activity and centralspindlin assembly during abscission, and how its cytokinetic versus signaling roles are mechanistically partitioned, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified structural model of regulated MKLP1 motor activation\", \"Tail autoinhibition mechanism unestablished in reliable literature\", \"Causal separation of cytokinetic and oncogenic signaling functions lacking\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [4, 14]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [4, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 20, 23]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [4, 9]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [12, 13, 27]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [6, 20]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2, 3, 4, 8]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [23, 31]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [14, 26]}\n    ],\n    \"complexes\": [\"centralspindlin\"],\n    \"partners\": [\"RACGAP1\", \"PLK1\", \"AURKB\", \"INCENP\", \"ARF6\", \"CTNND1\", \"AMER1\", \"MYH9\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}