{"gene":"KIF23","run_date":"2026-04-28T18:30:27","timeline":{"discoveries":[{"year":1995,"finding":"PLK1 (Plk) physically interacts with CHO1/MKLP1 (KIF23) in vivo during late M phase, colocalizing at the midbody, and CHO1/MKLP1 is phosphorylated by Plk-associated kinase activity in vitro. CHO1/MKLP1 induces microtubule bundling and antiparallel movement in vitro.","method":"Co-immunoprecipitation, in vitro kinase assay, immunofluorescence colocalization","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 — reciprocal Co-IP, in vitro kinase assay, and colocalization; foundational paper with 245 citations","pmids":["8524282"],"is_preprint":false},{"year":2004,"finding":"PLK1 binds CHO1/MKLP1 (KIF23) via its Polo-box domain, while the stalk domain of CHO1/MKLP1 mediates binding to PLK1. Ser904 and Ser905 are the two major PLK1 phosphorylation sites on CHO1/MKLP1. Depletion of CHO1/MKLP1 causes multinucleation and mislocalizes PLK1 during late mitosis; overexpression of a non-phosphorylatable mutant causes cytokinesis defects; rescue requires the phosphorylatable form.","method":"Transient transfection domain-mapping, in vitro kinase assay with phosphosite mutagenesis, siRNA knockdown, immunofluorescence, rescue experiments","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including mutagenesis, kinase assay, and functional rescue in a single study","pmids":["15199097"],"is_preprint":false},{"year":2005,"finding":"Aurora B phosphorylates MKLP1 (KIF23) on conserved C-terminal serine residues in vitro and in vivo. A non-phosphorylatable MKLP1 mutant localizes properly but fails to support completion of cytokinesis. Aurora B inhibition in late anaphase attenuates MKLP1 phosphorylation and causes cytokinesis failure without disrupting the central spindle.","method":"In vitro kinase assay, phosphosite mutagenesis, Aurora kinase inhibitor treatment, live-cell imaging, C. elegans genetics and human cell culture","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 1 — in vitro kinase assay + mutagenesis + in vivo validation; replicated in two organisms","pmids":["15854913"],"is_preprint":false},{"year":2005,"finding":"INCENP is required for recruiting MKLP1 (KIF23) to the spindle midzone/midbody. MKLP1 depletion by siRNA does not disrupt chromosome segregation or midzone formation but abrogates midbody formation and completion of cytokinesis. INCENP depletion disrupts midzone/midbody formation and causes binucleation.","method":"RNAi/siRNA knockdown, immunofluorescence, live-cell imaging, 3D reconstruction","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 2 — clean siRNA knockdowns with defined cellular phenotypes, live imaging, and 3D reconstruction","pmids":["15796717"],"is_preprint":false},{"year":1999,"finding":"GTP-bound (activated) Arf proteins directly bind the C-terminal tail domain of MKLP1 (KIF23) via switch I and switch II regions. An 88-amino acid domain in the MKLP1 C-terminus is sufficient for GTP-dependent Arf binding, and all human Arf isoforms interact with this domain.","method":"Yeast two-hybrid screen, deletion mapping, GST pull-down assay, point mutagenesis of Arf switch regions","journal":"Cell motility and the cytoskeleton","confidence":"High","confidence_rationale":"Tier 1–2 — yeast two-hybrid plus GST pulldown with mutagenesis, multiple Arf isoforms tested","pmids":["10506747"],"is_preprint":false},{"year":2012,"finding":"Arf6 directly interacts with MKLP1 (KIF23) at the Flemming body/midbody. Crystal structure of the Arf6-MKLP1 complex shows MKLP1 forms a homodimer flanked by two Arf6 molecules (2:2 heterotetramer) with an extended β-sheet spanning the complex, suitable for membrane interaction at the cleavage furrow. Structure-based mutagenesis and siRNA knockdowns confirm that complex formation is required for completion of cytokinesis.","method":"Crystal structure determination, structure-based mutagenesis, siRNA knockdown, immunofluorescence","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 — crystal structure plus functional mutagenesis plus siRNA validation; multiple orthogonal methods","pmids":["22522702"],"is_preprint":false},{"year":2007,"finding":"Centralspindlin is a heterotetrameric complex composed of two CYK-4/MgcRacGAP homodimers (via parallel coiled coil) and two ZEN-4/MKLP1 homodimers (via parallel coiled coil), assembled through two low-affinity interactions. Centralspindlin (but not individual subunits alone) is sufficient to bundle microtubules in vitro.","method":"Biochemical dissection, in vitro microtubule bundling assay, conditional genetic mutations and suppressor screen in C. elegans","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 — reconstitution in vitro plus genetic epistasis; foundational complex assembly study","pmids":["17942600"],"is_preprint":false},{"year":2013,"finding":"TRAF6 E3 ubiquitin ligase mediates ubiquitination of KIF23/MKLP1 at the midbody ring. SQSTM1/p62 and WDFY3/ALFY form a complex with TRAF6, and these proteins plus NBR1 are required for clearance of midbody ring derivatives by selective autophagy. TRAF6 depletion reduces ubiquitinated midbody ring derivatives.","method":"siRNA knockdown, immunofluorescence, autophagy assays","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2–3 — siRNA knockdown with quantified phenotypic readout; single lab","pmids":["24128730"],"is_preprint":false},{"year":2013,"finding":"A missense mutation in KIF23 (p.P916R) causes autosomal dominant congenital dyserythropoietic anemia type III (CDA III). RNAi-based knockdown and rescue experiments in HeLa cells demonstrate that the p.P916R mutation causes cytokinesis failure, consistent with large multinucleated erythroblasts observed in patients.","method":"Targeted next-generation sequencing, RNAi knockdown, mutant rescue in HeLa cells, haplotype analysis","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 — genetic linkage plus functional knockdown/rescue; segregation in two families plus in vitro functional validation","pmids":["23570799"],"is_preprint":false},{"year":1998,"finding":"CHO1/MKLP1 (KIF23) is required for establishing nonuniform microtubule polarity in podocyte processes. Antisense oligonucleotide treatment in differentiating podocytes abolishes both process formation and nonuniform MT polarity. CHO1/MKLP1 associates with microtubules in podocytes during process formation.","method":"Antisense oligonucleotide treatment, hook-decoration MT polarity assay, immunofluorescence, taxol/nocodazole recovery experiments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — loss-of-function with specific phenotypic readout plus direct MT polarity assay; multiple orthogonal methods","pmids":["9864367"],"is_preprint":false},{"year":1998,"finding":"CHO1/MKLP1 (KIF23) is expressed in postmitotic neurons (in vivo and in vitro), with mRNA levels peaking prior to dendritic development and declining after dendrites differentiate. Dorsal root ganglion neurons (axon-only) express significantly lower levels, consistent with a role in establishing the dendritic minus-end-distal microtubule polarity pattern.","method":"In situ hybridization in rodent brain, in vitro hippocampal neuron culture, quantitative expression analysis","journal":"The European journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 3 — expression with correlated functional inference; no direct loss-of-function in neurons in this paper","pmids":["9749792"],"is_preprint":false},{"year":2006,"finding":"MKLP1 (KIF23) nuclear localization during interphase requires two NLS sequences (899SRKRRSST906 and 949KRKKP953) in its tail domain. Expression of an NLS-deleted mutant causes cell cycle arrest at cytokinesis. Phosphomimetic mutations at two serines within the first NLS attenuate nuclear localization, suggesting phosphorylation-regulated nuclear import.","method":"Domain mapping by mutagenesis, ectopic expression of NLS mutants, cell cycle analysis","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — mutagenesis with functional cytokinesis phenotype; single lab, single study","pmids":["17198681"],"is_preprint":false},{"year":2006,"finding":"The motor and tail domains of MKLP1 (KIF23) are required for its dendritic targeting in hippocampal neurons. Deletion of the motor domain prevents dendritic distribution; deletion of the tail domain causes axonal mislocalization; deletion of the stalk domain still permits dendritic targeting.","method":"eGFP-tagged domain deletion mutants expressed in primary hippocampal neurons, fluorescence microscopy","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 — domain deletion analysis with localization readout; single lab, well-defined structural dissection","pmids":["16418225"],"is_preprint":false},{"year":2015,"finding":"Kif23 isoform CHO1 (but not the shorter MKLP1 isoform) contains two NDR/LATS kinase consensus sites (S716 and S814) that are phosphorylated by NDR and LATS kinases in vitro. Phosphorylation at S814 creates a 14-3-3 binding site important for Kif23 clustering during cytokinesis. Sequential phosphorylation occurs: S716 phosphorylation is required for efficient S814 phosphorylation. LATS1/2 participate in S814 phosphorylation in vivo.","method":"In vitro kinase assay with NDR/LATS, site-directed mutagenesis, 14-3-3 binding assay, in vivo phosphorylation analysis","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1 — in vitro kinase assay with mutagenesis plus in vivo validation; multiple orthogonal methods","pmids":["25658096"],"is_preprint":false},{"year":2016,"finding":"p120-catenin binds MKLP1 (KIF23) via its N-terminal coiled-coil domain (isoform 1A) at the cleavage furrow during anaphase to spatially control RhoA GTPase cycling. This binding is independent of cadherin association. Loss of p120 leads to multinucleation due to cytokinesis failure.","method":"Co-immunoprecipitation, domain mutagenesis, immunofluorescence, siRNA knockdown with multinucleation readout","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP plus domain mutagenesis plus loss-of-function with specific phenotype","pmids":["28004812"],"is_preprint":false},{"year":2013,"finding":"KIF23 transcription is regulated by p53 via p21(WAF1/CIP1)-dependent repression. The cell cycle genes homology region (CHR) element in the KIF23 promoter is required for both p53-dependent repression and cell cycle-dependent expression. DREAM and MMB complexes differentially bind the CHR element to control cell cycle- and p53-dependent regulation of KIF23.","method":"Promoter reporter assays, qRT-PCR, Western blot, chromatin immunoprecipitation","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — promoter mutagenesis plus ChIP plus reporter assays; single lab","pmids":["23650552"],"is_preprint":false},{"year":2008,"finding":"CUX1 and E2F1 transcription factors cooperatively bind the MKLP1 (KIF23) promoter upon S-phase entry, driving its transcriptional activation. The KIF23 promoter contains CHR sites, E2F binding elements, and CUX1 binding sites. CUX1 or E2F1 overexpression increases endogenous MKLP1 protein; E2F1 knockdown reduces it.","method":"Chromatin immunoprecipitation, promoter-luciferase reporter assays, dominant negative/overexpression of transcription factors, siRNA","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — ChIP plus reporter assays plus gain/loss-of-function; multiple orthogonal methods","pmids":["19015243"],"is_preprint":false},{"year":2024,"finding":"SIRT7 physically interacts with KIF23 and inhibits its succinylation at K537, thereby enhancing KIF23 protein stability. Overexpression of SIRT7 increases KIF23 protein levels in HEK-293T cells, and SIRT7 knockdown blocks the pro-proliferative and pro-migratory effects of KIF23 overexpression in anaplastic thyroid cancer cells.","method":"Co-immunoprecipitation, Western blot for succinylation, protein stability assay, siRNA knockdown, overexpression","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP plus post-translational modification assay; single lab","pmids":["38360598"],"is_preprint":false},{"year":2020,"finding":"KIF23 activates Wnt/β-catenin signaling in gastric cancer by directly interacting with Amer1, competitively blocking Amer1-APC association, and relocating Amer1 from the membrane/cytoplasm to the nucleus, thereby attenuating Amer1's negative regulation of Wnt/β-catenin signaling.","method":"Co-immunoprecipitation, immunofluorescence, siRNA knockdown, cell function assays, TCGA/GEO data analysis","journal":"Aging","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP for direct interaction plus localization shift; mechanistic follow-up in cancer cells","pmids":["32365332"],"is_preprint":false},{"year":2020,"finding":"The tail domain of MKLP1 (KIF23) exhibits an autoinhibitory effect on its motor activity; overexpression of the tail domain alone blocks cytokinesis and causes binucleation. PAK2 (p21-activated kinase 2) binds the MKLP1 tail domain, and PAK2 knockdown causes loss of MKLP1 midbody localization and cytokinesis failure, suggesting PAK2 binding relieves autoinhibition.","method":"GST pull-down, LC-MS/MS interactome, co-immunoprecipitation, FRET, siRNA knockdown, overexpression in HEK293 cells","journal":"BioMed research international","confidence":"Low","confidence_rationale":"Tier 3 — Co-IP/FRET plus siRNA phenotype, but paper was subsequently retracted (PMID 38550036)","pmids":["33204722"],"is_preprint":false},{"year":2022,"finding":"FOXM1 epigenetically activates KIF23 expression in hepatocellular carcinoma by increasing RNA polymerase II occupancy and histone H3K27 acetylation at the KIF23 promoter. FOXM1 suppression reduces KIF23 levels and reverses sorafenib resistance.","method":"ChIP for RNA Pol II and H3K27ac at KIF23 promoter, Western blot, siRNA knockdown","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — ChIP evidence for epigenetic regulation plus functional readout; single lab","pmids":["36940637"],"is_preprint":false},{"year":2022,"finding":"NAT10 binds the 3'UTR of KIF23 mRNA and up-regulates its ac4C modification, stabilizing KIF23 mRNA and increasing KIF23 protein levels, which in turn activates Wnt/β-catenin signaling via GSK-3β/β-catenin to promote colorectal cancer progression.","method":"RIP-seq, acRIP-seq, RNA stability assays, luciferase reporter assay, Western blot, in vitro and in vivo cancer models","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 2 — RIP-seq plus acRIP-seq plus reporter assay; multiple orthogonal methods in a single lab","pmids":["36522719"],"is_preprint":false},{"year":2024,"finding":"KIF23 depletion in mice disrupts mitotic spindle orientation and impairs cytokinesis in neural stem and progenitor cells (NSPCs), leading to precocious neurogenesis, neuronal apoptosis, accelerated cell cycle exit, and disrupted apical junction protein localization. Phenotypes are rescued by wild-type human KIF23 but not by a microcephaly-associated variant, establishing KIF23 as required for spindle orientation and apical surface maintenance in cortical NSPCs.","method":"Kif23 knockdown in mouse cortex, rescue with WT vs. disease-variant human KIF23, live imaging, immunofluorescence for spindle orientation and apical junction proteins","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — loss-of-function with defined phenotype plus rescue with wild-type vs. disease variant; multiple readouts","pmids":["39632980"],"is_preprint":false},{"year":2022,"finding":"Centralspindlin (Cyk4/MKLP1) and its partner RhoGEF Ect2 are required for exclusion of NuMA/dynein/dynactin from the equatorial cell membrane during anaphase. Ect2-based and NuMA-based complexes occupy mutually exclusive membrane domains; equatorial enrichment of the Ect2/Cyk4/Mklp1 complex is essential for proper spindle elongation and cleavage furrow formation.","method":"siRNA knockdown, immunofluorescence, live-cell imaging of membrane compartmentalization","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — genetic knockdown with defined localization and functional phenotype; single lab","pmids":["36197340"],"is_preprint":false},{"year":2025,"finding":"Kif23 promotes cardiac fibroblast proliferation and myofibroblast transdifferentiation following myocardial infarction by activating RhoA and suppressing Ces1d-mediated fatty acid β-oxidation via the RhoA/ROCK1 signaling axis, causing pathological lipid accumulation and fibrosis. Kif23 knockdown (via AAV-shRNA) attenuated post-MI fibrosis in mice.","method":"AAV-mediated shRNA knockdown in vivo, TGF-β1-stimulated cardiac fibroblasts, proteomic profiling, lipid droplet analysis, Western blot for RhoA/ROCK1","journal":"Hypertension (Dallas, Tex. : 1979)","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo knockdown plus in vitro mechanistic assays; proteomic identification of downstream effector","pmids":["41078122"],"is_preprint":false},{"year":2023,"finding":"In hepatocellular carcinoma, the TAZ-TEAD2 transcriptional pathway promotes tumor cell proliferation via increased expression of KIF23 (and ANLN) as direct transcriptional targets. CRISPRi knockdown of KIF23 in mice reduced HCC tumor growth, and TAZ deletion consistently decreased HCC growth and mortality.","method":"CRISPRi screen, ChIP to confirm TAZ target genes, RNA sequencing, genetic deletion of TAZ in floxed mice, AAV8-Cre delivery","journal":"Gastroenterology","confidence":"Medium","confidence_rationale":"Tier 2 — CRISPRi screen plus ChIP plus in vivo genetic models; TAZ→TEAD2→KIF23 axis established","pmids":["36894036"],"is_preprint":false},{"year":2016,"finding":"In Drosophila motoneurons, Toll-6/dSARM/FoxO signaling represses Pavarotti/MKLP1 (ortholog of KIF23) expression. Elevated MKLP1 attenuates microtubule dynamics. Pathway loss-of-function phenotypes in axon transport and structural plasticity are rescued by reducing Pav-KLP expression, placing MKLP1 downstream of Toll-6-FoxO signaling.","method":"Drosophila genetic epistasis (suppressor analysis), in vivo imaging, Western blot","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis in Drosophila ortholog with in vivo functional rescue","pmids":["27502486"],"is_preprint":false},{"year":2026,"finding":"The C-terminal domain of KIF23 directly binds the myosin tail domain of MYH9. This interaction stabilizes MYH9 by recruiting deubiquitinase USP7 to remove K48-linked ubiquitin chains from MYH9. Stabilized MYH9 then recruits USP15 to deubiquitinate MCM2 at K469, preventing MCM2 degradation. Elevated MCM2 enhances binding to PCNA, promoting cervical cancer cell proliferation and cisplatin resistance.","method":"Co-immunoprecipitation, CRISPR/Cas9 knockout, protein half-life assay, ubiquitination assay, domain mapping","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP with domain mapping, ubiquitination assays, and KO phenotype; single lab but multiple orthogonal methods","pmids":["41940421"],"is_preprint":false},{"year":2025,"finding":"CDK1 and Aurora B phosphorylation of Citron kinase (CIT-K) at S440 and S699 reduces CIT-K's ability to interact with its midbody partners including KIF23/MKLP1 (and KIF14 and AURKB), thereby regulating midbody formation and post-mitotic midbody remnant stability.","method":"Phosphosite mutagenesis, Co-immunoprecipitation, in vitro kinase assay, live-cell imaging","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1–2 — in vitro kinase assay plus mutagenesis plus Co-IP; preprint only","pmids":[],"is_preprint":true}],"current_model":"KIF23/MKLP1 is a kinesin-6 motor protein that forms the centralspindlin heterotetramer with CYK-4/MgcRacGAP; it bundles antiparallel microtubules at the central spindle/midbody during cytokinesis, where it is regulated by phosphorylation from Aurora B (on C-terminal serines required for cytokinesis completion), PLK1 (on Ser904/905 via the polo-box/stalk interaction required for proper cytokinesis), and LATS/NDR kinases (sequential S716→S814 phosphorylation controlling 14-3-3 binding and clustering); it interacts with Arf6 (whose crystal structure reveals a 2:2 heterotetramer connecting microtubule bundles to membranes at the cleavage furrow), INCENP (for midzone/midbody recruitment), p120-catenin (for spatial RhoA control), and PAK2 (potentially relieving tail-domain autoinhibition); in interphase it localizes to the nucleus via two NLS sequences whose function can be regulated by phosphorylation; KIF23 is also expressed postmitotically in neurons and podocytes to establish nonuniform microtubule polarity required for dendrite and process formation; mutations in KIF23 (e.g., p.P916R) cause cytokinesis failure and congenital dyserythropoietic anemia type III; and its expression is transcriptionally controlled by the p53/p21/DREAM-MMB/CHR axis and by CUX1/E2F1, while post-transcriptionally it is stabilized by NAT10-mediated ac4C mRNA modification and SIRT7-mediated desuccinylation."},"narrative":{"teleology":[{"year":1995,"claim":"Identifying PLK1 as a mitotic-phase interactor and kinase for KIF23 established the first regulatory connection between a mitotic kinase and a kinesin motor at the midbody, explaining how cytokinesis-specific motor activation might be achieved.","evidence":"Co-IP, in vitro kinase assay, and immunofluorescence colocalization in mammalian cells","pmids":["8524282"],"confidence":"High","gaps":["Specific phosphorylation sites not mapped","Functional consequence of PLK1 phosphorylation on cytokinesis not tested"]},{"year":1998,"claim":"Demonstrating that KIF23 is expressed postmitotically in neurons and podocytes, and is required for nonuniform microtubule polarity in podocyte processes, revealed a cell-division-independent function for this motor in organizing microtubule arrays for cell morphogenesis.","evidence":"Antisense oligonucleotide knockdown in podocytes with hook-decoration MT polarity assay; in situ hybridization and expression analysis in rodent neurons","pmids":["9864367","9749792"],"confidence":"High","gaps":["No direct loss-of-function in neurons at this stage","Mechanism by which KIF23 establishes minus-end-distal polarity not defined"]},{"year":1999,"claim":"Discovery that GTP-bound Arf proteins directly bind the KIF23 C-terminal tail provided the first link between this motor and membrane trafficking machinery, suggesting a mechanism for coupling microtubule organization to membrane delivery at the cleavage furrow.","evidence":"Yeast two-hybrid, GST pull-down with Arf switch-region mutants","pmids":["10506747"],"confidence":"High","gaps":["Structural basis of the interaction unknown","In vivo relevance for cytokinesis not tested"]},{"year":2004,"claim":"Mapping PLK1 phosphorylation to Ser904/905 and demonstrating that non-phosphorylatable KIF23 causes cytokinesis failure established that PLK1-mediated phosphorylation is functionally required, not merely correlative.","evidence":"In vitro kinase assay with phosphosite mutagenesis, siRNA knockdown, rescue experiments in mammalian cells","pmids":["15199097"],"confidence":"High","gaps":["Whether PLK1 phosphorylation regulates motor activity vs. localization vs. protein interactions not distinguished"]},{"year":2005,"claim":"Identifying Aurora B as a second essential kinase for KIF23 — phosphorylating C-terminal serines required for cytokinesis completion but not midzone localization — separated localization from activation and revealed a two-kinase regulatory logic; simultaneously, INCENP was shown to be required for KIF23 midzone recruitment, defining the recruitment pathway.","evidence":"In vitro kinase assay, phosphosite mutagenesis, Aurora kinase inhibitor in C. elegans and human cells; siRNA knockdowns with live-cell imaging and 3D reconstruction","pmids":["15854913","15796717"],"confidence":"High","gaps":["Substrates downstream of KIF23 phosphorylation at these sites not identified","How INCENP recruits KIF23 molecularly not resolved"]},{"year":2006,"claim":"Defining the motor and tail domain requirements for dendritic targeting of KIF23, and identifying two NLS sequences required for interphase nuclear import regulated by phosphorylation, revealed how domain architecture controls both neuronal and cell-cycle-dependent KIF23 trafficking.","evidence":"GFP-tagged domain deletion mutants in hippocampal neurons; NLS mutagenesis with cell cycle analysis in mammalian cells","pmids":["16418225","17198681"],"confidence":"Medium","gaps":["Identity of the kinase(s) phosphorylating the NLS in vivo unknown","No loss-of-function phenotype for NLS-deleted KIF23 in neurons"]},{"year":2007,"claim":"Biochemical reconstitution of centralspindlin as a CYK-4/KIF23 heterotetramer that is necessary and sufficient for microtubule bundling resolved the stoichiometry and established centralspindlin — not KIF23 alone — as the functional unit for central spindle organization.","evidence":"In vitro reconstitution, microtubule bundling assay, conditional genetics and suppressor screen in C. elegans","pmids":["17942600"],"confidence":"High","gaps":["High-resolution structure of the full complex not available","How centralspindlin is targeted specifically to antiparallel overlaps in vivo not resolved"]},{"year":2008,"claim":"Demonstrating that CUX1 and E2F1 cooperatively activate the KIF23 promoter upon S-phase entry established the transcriptional basis for cell-cycle-dependent KIF23 expression.","evidence":"ChIP, promoter-luciferase assays, overexpression and siRNA of CUX1/E2F1","pmids":["19015243"],"confidence":"High","gaps":["Whether CUX1/E2F1 regulation is sufficient in all cell types not tested"]},{"year":2012,"claim":"The crystal structure of the Arf6–KIF23 complex as a 2:2 heterotetramer with a membrane-binding β-sheet surface provided a structural mechanism for how the motor bridges microtubule bundles to membranes at the cleavage furrow.","evidence":"X-ray crystallography, structure-based mutagenesis, siRNA knockdowns","pmids":["22522702"],"confidence":"High","gaps":["Membrane lipid specificity of the complex not defined","How Arf6 activation is spatially coupled to KIF23 localization in vivo not resolved"]},{"year":2013,"claim":"Identification of the KIF23 p.P916R mutation as the cause of autosomal dominant CDA III, validated by rescue experiments showing cytokinesis failure, linked the motor's molecular function to human disease and erythropoiesis.","evidence":"Targeted sequencing, haplotype analysis in families, RNAi knockdown and mutant rescue in HeLa cells","pmids":["23570799"],"confidence":"High","gaps":["Structural/biochemical mechanism by which P916R disrupts function not determined","No erythroid-specific cellular model used"]},{"year":2013,"claim":"Demonstrating p53/p21/DREAM-MMB/CHR-dependent transcriptional repression of KIF23 established the tumor suppressor pathway controlling KIF23 expression and explained why KIF23 is upregulated in p53-deficient cancers.","evidence":"Promoter reporter assays with CHR mutagenesis, ChIP for DREAM/MMB complexes, qRT-PCR","pmids":["23650552"],"confidence":"Medium","gaps":["Relative contributions of DREAM vs. CUX1/E2F1 not integrated","Whether CHR-mediated regulation occurs in non-transformed cells not confirmed"]},{"year":2015,"claim":"Identifying NDR/LATS kinases as regulators of sequential KIF23 phosphorylation (S716→S814) creating a 14-3-3 binding site revealed a Hippo-pathway-linked mechanism controlling KIF23 clustering during cytokinesis.","evidence":"In vitro kinase assays, phosphosite mutagenesis, 14-3-3 binding assays, in vivo phosphorylation analysis","pmids":["25658096"],"confidence":"High","gaps":["Whether LATS kinase regulation of KIF23 connects to canonical Hippo pathway tumor suppression not explored","Functional consequence of 14-3-3 binding on motor activity or localization not fully resolved"]},{"year":2016,"claim":"Demonstrating that p120-catenin binds KIF23 at the cleavage furrow to spatially control RhoA cycling connected the adherens junction scaffold to cytokinetic RhoA regulation, explaining how cell-cell adhesion components influence division.","evidence":"Reciprocal Co-IP, domain mutagenesis, siRNA knockdown with multinucleation phenotype","pmids":["28004812"],"confidence":"High","gaps":["Whether this mechanism operates in epithelial tissues in vivo not tested","Molecular details of how p120/KIF23 interaction modulates Ect2 or CYK-4 GAP activity unclear"]},{"year":2022,"claim":"Discovery that centralspindlin/Ect2 excludes NuMA/dynein from the equatorial membrane revealed a spatial antagonism mechanism by which KIF23-containing complexes define cleavage furrow identity by segregating cortical force generators.","evidence":"siRNA knockdowns, immunofluorescence of membrane domain compartmentalization, live-cell imaging","pmids":["36197340"],"confidence":"Medium","gaps":["Biochemical basis for mutual exclusion between centralspindlin/Ect2 and NuMA/dynein complexes not defined","Whether this mechanism operates in asymmetric divisions not tested"]},{"year":2022,"claim":"Post-transcriptional regulation of KIF23 by NAT10-mediated ac4C mRNA modification and transcriptional activation by FOXM1 or TAZ-TEAD2 revealed multiple cancer-relevant pathways converging to elevate KIF23 expression.","evidence":"RIP-seq and acRIP-seq for NAT10/ac4C; ChIP for FOXM1 at KIF23 promoter; CRISPRi screen identifying KIF23 as TAZ-TEAD2 target","pmids":["36522719","36940637","36894036"],"confidence":"Medium","gaps":["Whether these regulatory pathways operate independently or synergistically not determined","Relative contribution of transcriptional vs. post-transcriptional regulation to KIF23 protein levels in normal cells unknown"]},{"year":2024,"claim":"KIF23 depletion in mouse cortex disrupted spindle orientation and apical junction integrity in neural stem cells — rescued by wild-type but not a microcephaly variant — establishing KIF23 as required for cortical neurogenesis beyond its canonical cytokinesis role.","evidence":"In vivo knockdown in mouse cortex, rescue with WT vs. disease-variant human KIF23, live imaging, immunofluorescence","pmids":["39632980"],"confidence":"High","gaps":["Whether spindle orientation defect is independent of the cytokinesis role not fully separated","Identity and mechanism of the microcephaly-associated variant not fully characterized"]},{"year":null,"claim":"The mechanism by which KIF23 motor activity is autoinhibited and relieved in vivo, the structural basis of full-length centralspindlin, and how KIF23's multiple post-translational modifications are integrated to coordinate cytokinesis progression remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structure of full-length centralspindlin or autoinhibited KIF23","Integration of PLK1, Aurora B, and LATS phosphorylation events temporally and functionally not resolved","Autoinhibition mechanism rests on a retracted paper (PMID:33204722) and awaits independent confirmation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,6]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[6,9]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,3,6]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[11]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,2,3,6,13,14]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[18,21,24]}],"complexes":["centralspindlin (CYK-4/MKLP1 heterotetramer)"],"partners":["RACGAP1","PLK1","ARF6","INCENP","CTNND1","AURKB","MYH9","SIRT7"],"other_free_text":[]},"mechanistic_narrative":"KIF23 (MKLP1/CHO1) is a kinesin-6 family motor protein that functions as an essential organizer of the central spindle and midbody during cytokinesis, with additional postmitotic roles in establishing nonuniform microtubule polarity in neurons and podocytes. It forms the centralspindlin heterotetramer with CYK-4/MgcRacGAP, which is necessary and sufficient for antiparallel microtubule bundling [PMID:17942600], and its proper function requires phosphorylation by PLK1 at Ser904/905 [PMID:15199097], Aurora B on C-terminal serines [PMID:15854913], and NDR/LATS kinases at S716/S814 controlling 14-3-3 binding and clustering [PMID:25658096], as well as INCENP-dependent recruitment to the midzone [PMID:15796717] and Arf6 interaction at the midbody via a structurally defined 2:2 heterotetramer that bridges microtubule bundles to membranes [PMID:22522702]. KIF23 transcription is cell-cycle regulated through the p53/p21/DREAM-MMB/CHR axis [PMID:23650552] and CUX1/E2F1 [PMID:19015243], while its mRNA is post-transcriptionally stabilized by NAT10-mediated ac4C modification [PMID:36522719] and its protein by SIRT7-mediated desuccinylation [PMID:38360598]. A missense mutation (p.P916R) in KIF23 causes autosomal dominant congenital dyserythropoietic anemia type III through cytokinesis failure [PMID:23570799]."},"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. 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phase, colocalizing at the midbody, and CHO1/MKLP1 is phosphorylated by Plk-associated kinase activity in vitro. CHO1/MKLP1 induces microtubule bundling and antiparallel movement in vitro.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, immunofluorescence colocalization\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reciprocal Co-IP, in vitro kinase assay, and colocalization; foundational paper with 245 citations\",\n      \"pmids\": [\"8524282\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"PLK1 binds CHO1/MKLP1 (KIF23) via its Polo-box domain, while the stalk domain of CHO1/MKLP1 mediates binding to PLK1. Ser904 and Ser905 are the two major PLK1 phosphorylation sites on CHO1/MKLP1. Depletion of CHO1/MKLP1 causes multinucleation and mislocalizes PLK1 during late mitosis; overexpression of a non-phosphorylatable mutant causes cytokinesis defects; rescue requires the phosphorylatable form.\",\n      \"method\": \"Transient transfection domain-mapping, in vitro kinase assay with phosphosite mutagenesis, siRNA knockdown, immunofluorescence, rescue experiments\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including mutagenesis, kinase assay, and functional rescue in a single study\",\n      \"pmids\": [\"15199097\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Aurora B phosphorylates MKLP1 (KIF23) on conserved C-terminal serine residues in vitro and in vivo. A non-phosphorylatable MKLP1 mutant localizes properly but fails to support completion of cytokinesis. Aurora B inhibition in late anaphase attenuates MKLP1 phosphorylation and causes cytokinesis failure without disrupting the central spindle.\",\n      \"method\": \"In vitro kinase assay, phosphosite mutagenesis, Aurora kinase inhibitor treatment, live-cell imaging, C. elegans genetics and human cell culture\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro kinase assay + mutagenesis + in vivo validation; replicated in two organisms\",\n      \"pmids\": [\"15854913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"INCENP is required for recruiting MKLP1 (KIF23) to the spindle midzone/midbody. MKLP1 depletion by siRNA does not disrupt chromosome segregation or midzone formation but abrogates midbody formation and completion of cytokinesis. INCENP depletion disrupts midzone/midbody formation and causes binucleation.\",\n      \"method\": \"RNAi/siRNA knockdown, immunofluorescence, live-cell imaging, 3D reconstruction\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean siRNA knockdowns with defined cellular phenotypes, live imaging, and 3D reconstruction\",\n      \"pmids\": [\"15796717\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"GTP-bound (activated) Arf proteins directly bind the C-terminal tail domain of MKLP1 (KIF23) via switch I and switch II regions. An 88-amino acid domain in the MKLP1 C-terminus is sufficient for GTP-dependent Arf binding, and all human Arf isoforms interact with this domain.\",\n      \"method\": \"Yeast two-hybrid screen, deletion mapping, GST pull-down assay, point mutagenesis of Arf switch regions\",\n      \"journal\": \"Cell motility and the cytoskeleton\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — yeast two-hybrid plus GST pulldown with mutagenesis, multiple Arf isoforms tested\",\n      \"pmids\": [\"10506747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Arf6 directly interacts with MKLP1 (KIF23) at the Flemming body/midbody. Crystal structure of the Arf6-MKLP1 complex shows MKLP1 forms a homodimer flanked by two Arf6 molecules (2:2 heterotetramer) with an extended β-sheet spanning the complex, suitable for membrane interaction at the cleavage furrow. Structure-based mutagenesis and siRNA knockdowns confirm that complex formation is required for completion of cytokinesis.\",\n      \"method\": \"Crystal structure determination, structure-based mutagenesis, siRNA knockdown, immunofluorescence\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure plus functional mutagenesis plus siRNA validation; multiple orthogonal methods\",\n      \"pmids\": [\"22522702\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Centralspindlin is a heterotetrameric complex composed of two CYK-4/MgcRacGAP homodimers (via parallel coiled coil) and two ZEN-4/MKLP1 homodimers (via parallel coiled coil), assembled through two low-affinity interactions. Centralspindlin (but not individual subunits alone) is sufficient to bundle microtubules in vitro.\",\n      \"method\": \"Biochemical dissection, in vitro microtubule bundling assay, conditional genetic mutations and suppressor screen in C. elegans\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — reconstitution in vitro plus genetic epistasis; foundational complex assembly study\",\n      \"pmids\": [\"17942600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TRAF6 E3 ubiquitin ligase mediates ubiquitination of KIF23/MKLP1 at the midbody ring. SQSTM1/p62 and WDFY3/ALFY form a complex with TRAF6, and these proteins plus NBR1 are required for clearance of midbody ring derivatives by selective autophagy. TRAF6 depletion reduces ubiquitinated midbody ring derivatives.\",\n      \"method\": \"siRNA knockdown, immunofluorescence, autophagy assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — siRNA knockdown with quantified phenotypic readout; single lab\",\n      \"pmids\": [\"24128730\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"A missense mutation in KIF23 (p.P916R) causes autosomal dominant congenital dyserythropoietic anemia type III (CDA III). RNAi-based knockdown and rescue experiments in HeLa cells demonstrate that the p.P916R mutation causes cytokinesis failure, consistent with large multinucleated erythroblasts observed in patients.\",\n      \"method\": \"Targeted next-generation sequencing, RNAi knockdown, mutant rescue in HeLa cells, haplotype analysis\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic linkage plus functional knockdown/rescue; segregation in two families plus in vitro functional validation\",\n      \"pmids\": [\"23570799\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"CHO1/MKLP1 (KIF23) is required for establishing nonuniform microtubule polarity in podocyte processes. Antisense oligonucleotide treatment in differentiating podocytes abolishes both process formation and nonuniform MT polarity. CHO1/MKLP1 associates with microtubules in podocytes during process formation.\",\n      \"method\": \"Antisense oligonucleotide treatment, hook-decoration MT polarity assay, immunofluorescence, taxol/nocodazole recovery experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with specific phenotypic readout plus direct MT polarity assay; multiple orthogonal methods\",\n      \"pmids\": [\"9864367\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"CHO1/MKLP1 (KIF23) is expressed in postmitotic neurons (in vivo and in vitro), with mRNA levels peaking prior to dendritic development and declining after dendrites differentiate. Dorsal root ganglion neurons (axon-only) express significantly lower levels, consistent with a role in establishing the dendritic minus-end-distal microtubule polarity pattern.\",\n      \"method\": \"In situ hybridization in rodent brain, in vitro hippocampal neuron culture, quantitative expression analysis\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — expression with correlated functional inference; no direct loss-of-function in neurons in this paper\",\n      \"pmids\": [\"9749792\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"MKLP1 (KIF23) nuclear localization during interphase requires two NLS sequences (899SRKRRSST906 and 949KRKKP953) in its tail domain. Expression of an NLS-deleted mutant causes cell cycle arrest at cytokinesis. Phosphomimetic mutations at two serines within the first NLS attenuate nuclear localization, suggesting phosphorylation-regulated nuclear import.\",\n      \"method\": \"Domain mapping by mutagenesis, ectopic expression of NLS mutants, cell cycle analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — mutagenesis with functional cytokinesis phenotype; single lab, single study\",\n      \"pmids\": [\"17198681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The motor and tail domains of MKLP1 (KIF23) are required for its dendritic targeting in hippocampal neurons. Deletion of the motor domain prevents dendritic distribution; deletion of the tail domain causes axonal mislocalization; deletion of the stalk domain still permits dendritic targeting.\",\n      \"method\": \"eGFP-tagged domain deletion mutants expressed in primary hippocampal neurons, fluorescence microscopy\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — domain deletion analysis with localization readout; single lab, well-defined structural dissection\",\n      \"pmids\": [\"16418225\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Kif23 isoform CHO1 (but not the shorter MKLP1 isoform) contains two NDR/LATS kinase consensus sites (S716 and S814) that are phosphorylated by NDR and LATS kinases in vitro. Phosphorylation at S814 creates a 14-3-3 binding site important for Kif23 clustering during cytokinesis. Sequential phosphorylation occurs: S716 phosphorylation is required for efficient S814 phosphorylation. LATS1/2 participate in S814 phosphorylation in vivo.\",\n      \"method\": \"In vitro kinase assay with NDR/LATS, site-directed mutagenesis, 14-3-3 binding assay, in vivo phosphorylation analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro kinase assay with mutagenesis plus in vivo validation; multiple orthogonal methods\",\n      \"pmids\": [\"25658096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"p120-catenin binds MKLP1 (KIF23) via its N-terminal coiled-coil domain (isoform 1A) at the cleavage furrow during anaphase to spatially control RhoA GTPase cycling. This binding is independent of cadherin association. Loss of p120 leads to multinucleation due to cytokinesis failure.\",\n      \"method\": \"Co-immunoprecipitation, domain mutagenesis, immunofluorescence, siRNA knockdown with multinucleation readout\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus domain mutagenesis plus loss-of-function with specific phenotype\",\n      \"pmids\": [\"28004812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF23 transcription is regulated by p53 via p21(WAF1/CIP1)-dependent repression. The cell cycle genes homology region (CHR) element in the KIF23 promoter is required for both p53-dependent repression and cell cycle-dependent expression. DREAM and MMB complexes differentially bind the CHR element to control cell cycle- and p53-dependent regulation of KIF23.\",\n      \"method\": \"Promoter reporter assays, qRT-PCR, Western blot, chromatin immunoprecipitation\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — promoter mutagenesis plus ChIP plus reporter assays; single lab\",\n      \"pmids\": [\"23650552\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CUX1 and E2F1 transcription factors cooperatively bind the MKLP1 (KIF23) promoter upon S-phase entry, driving its transcriptional activation. The KIF23 promoter contains CHR sites, E2F binding elements, and CUX1 binding sites. CUX1 or E2F1 overexpression increases endogenous MKLP1 protein; E2F1 knockdown reduces it.\",\n      \"method\": \"Chromatin immunoprecipitation, promoter-luciferase reporter assays, dominant negative/overexpression of transcription factors, siRNA\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — ChIP plus reporter assays plus gain/loss-of-function; multiple orthogonal methods\",\n      \"pmids\": [\"19015243\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SIRT7 physically interacts with KIF23 and inhibits its succinylation at K537, thereby enhancing KIF23 protein stability. Overexpression of SIRT7 increases KIF23 protein levels in HEK-293T cells, and SIRT7 knockdown blocks the pro-proliferative and pro-migratory effects of KIF23 overexpression in anaplastic thyroid cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, Western blot for succinylation, protein stability assay, siRNA knockdown, overexpression\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP plus post-translational modification assay; single lab\",\n      \"pmids\": [\"38360598\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF23 activates Wnt/β-catenin signaling in gastric cancer by directly interacting with Amer1, competitively blocking Amer1-APC association, and relocating Amer1 from the membrane/cytoplasm to the nucleus, thereby attenuating Amer1's negative regulation of Wnt/β-catenin signaling.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, siRNA knockdown, cell function assays, TCGA/GEO data analysis\",\n      \"journal\": \"Aging\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP for direct interaction plus localization shift; mechanistic follow-up in cancer cells\",\n      \"pmids\": [\"32365332\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The tail domain of MKLP1 (KIF23) exhibits an autoinhibitory effect on its motor activity; overexpression of the tail domain alone blocks cytokinesis and causes binucleation. PAK2 (p21-activated kinase 2) binds the MKLP1 tail domain, and PAK2 knockdown causes loss of MKLP1 midbody localization and cytokinesis failure, suggesting PAK2 binding relieves autoinhibition.\",\n      \"method\": \"GST pull-down, LC-MS/MS interactome, co-immunoprecipitation, FRET, siRNA knockdown, overexpression in HEK293 cells\",\n      \"journal\": \"BioMed research international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — Co-IP/FRET plus siRNA phenotype, but paper was subsequently retracted (PMID 38550036)\",\n      \"pmids\": [\"33204722\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"FOXM1 epigenetically activates KIF23 expression in hepatocellular carcinoma by increasing RNA polymerase II occupancy and histone H3K27 acetylation at the KIF23 promoter. FOXM1 suppression reduces KIF23 levels and reverses sorafenib resistance.\",\n      \"method\": \"ChIP for RNA Pol II and H3K27ac at KIF23 promoter, Western blot, siRNA knockdown\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — ChIP evidence for epigenetic regulation plus functional readout; single lab\",\n      \"pmids\": [\"36940637\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NAT10 binds the 3'UTR of KIF23 mRNA and up-regulates its ac4C modification, stabilizing KIF23 mRNA and increasing KIF23 protein levels, which in turn activates Wnt/β-catenin signaling via GSK-3β/β-catenin to promote colorectal cancer progression.\",\n      \"method\": \"RIP-seq, acRIP-seq, RNA stability assays, luciferase reporter assay, Western blot, in vitro and in vivo cancer models\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — RIP-seq plus acRIP-seq plus reporter assay; multiple orthogonal methods in a single lab\",\n      \"pmids\": [\"36522719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIF23 depletion in mice disrupts mitotic spindle orientation and impairs cytokinesis in neural stem and progenitor cells (NSPCs), leading to precocious neurogenesis, neuronal apoptosis, accelerated cell cycle exit, and disrupted apical junction protein localization. Phenotypes are rescued by wild-type human KIF23 but not by a microcephaly-associated variant, establishing KIF23 as required for spindle orientation and apical surface maintenance in cortical NSPCs.\",\n      \"method\": \"Kif23 knockdown in mouse cortex, rescue with WT vs. disease-variant human KIF23, live imaging, immunofluorescence for spindle orientation and apical junction proteins\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined phenotype plus rescue with wild-type vs. disease variant; multiple readouts\",\n      \"pmids\": [\"39632980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Centralspindlin (Cyk4/MKLP1) and its partner RhoGEF Ect2 are required for exclusion of NuMA/dynein/dynactin from the equatorial cell membrane during anaphase. Ect2-based and NuMA-based complexes occupy mutually exclusive membrane domains; equatorial enrichment of the Ect2/Cyk4/Mklp1 complex is essential for proper spindle elongation and cleavage furrow formation.\",\n      \"method\": \"siRNA knockdown, immunofluorescence, live-cell imaging of membrane compartmentalization\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic knockdown with defined localization and functional phenotype; single lab\",\n      \"pmids\": [\"36197340\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Kif23 promotes cardiac fibroblast proliferation and myofibroblast transdifferentiation following myocardial infarction by activating RhoA and suppressing Ces1d-mediated fatty acid β-oxidation via the RhoA/ROCK1 signaling axis, causing pathological lipid accumulation and fibrosis. Kif23 knockdown (via AAV-shRNA) attenuated post-MI fibrosis in mice.\",\n      \"method\": \"AAV-mediated shRNA knockdown in vivo, TGF-β1-stimulated cardiac fibroblasts, proteomic profiling, lipid droplet analysis, Western blot for RhoA/ROCK1\",\n      \"journal\": \"Hypertension (Dallas, Tex. : 1979)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo knockdown plus in vitro mechanistic assays; proteomic identification of downstream effector\",\n      \"pmids\": [\"41078122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In hepatocellular carcinoma, the TAZ-TEAD2 transcriptional pathway promotes tumor cell proliferation via increased expression of KIF23 (and ANLN) as direct transcriptional targets. CRISPRi knockdown of KIF23 in mice reduced HCC tumor growth, and TAZ deletion consistently decreased HCC growth and mortality.\",\n      \"method\": \"CRISPRi screen, ChIP to confirm TAZ target genes, RNA sequencing, genetic deletion of TAZ in floxed mice, AAV8-Cre delivery\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — CRISPRi screen plus ChIP plus in vivo genetic models; TAZ→TEAD2→KIF23 axis established\",\n      \"pmids\": [\"36894036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In Drosophila motoneurons, Toll-6/dSARM/FoxO signaling represses Pavarotti/MKLP1 (ortholog of KIF23) expression. Elevated MKLP1 attenuates microtubule dynamics. Pathway loss-of-function phenotypes in axon transport and structural plasticity are rescued by reducing Pav-KLP expression, placing MKLP1 downstream of Toll-6-FoxO signaling.\",\n      \"method\": \"Drosophila genetic epistasis (suppressor analysis), in vivo imaging, Western blot\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis in Drosophila ortholog with in vivo functional rescue\",\n      \"pmids\": [\"27502486\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The C-terminal domain of KIF23 directly binds the myosin tail domain of MYH9. This interaction stabilizes MYH9 by recruiting deubiquitinase USP7 to remove K48-linked ubiquitin chains from MYH9. Stabilized MYH9 then recruits USP15 to deubiquitinate MCM2 at K469, preventing MCM2 degradation. Elevated MCM2 enhances binding to PCNA, promoting cervical cancer cell proliferation and cisplatin resistance.\",\n      \"method\": \"Co-immunoprecipitation, CRISPR/Cas9 knockout, protein half-life assay, ubiquitination assay, domain mapping\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP with domain mapping, ubiquitination assays, and KO phenotype; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"41940421\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CDK1 and Aurora B phosphorylation of Citron kinase (CIT-K) at S440 and S699 reduces CIT-K's ability to interact with its midbody partners including KIF23/MKLP1 (and KIF14 and AURKB), thereby regulating midbody formation and post-mitotic midbody remnant stability.\",\n      \"method\": \"Phosphosite mutagenesis, Co-immunoprecipitation, in vitro kinase assay, live-cell imaging\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 — in vitro kinase assay plus mutagenesis plus Co-IP; preprint only\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"KIF23/MKLP1 is a kinesin-6 motor protein that forms the centralspindlin heterotetramer with CYK-4/MgcRacGAP; it bundles antiparallel microtubules at the central spindle/midbody during cytokinesis, where it is regulated by phosphorylation from Aurora B (on C-terminal serines required for cytokinesis completion), PLK1 (on Ser904/905 via the polo-box/stalk interaction required for proper cytokinesis), and LATS/NDR kinases (sequential S716→S814 phosphorylation controlling 14-3-3 binding and clustering); it interacts with Arf6 (whose crystal structure reveals a 2:2 heterotetramer connecting microtubule bundles to membranes at the cleavage furrow), INCENP (for midzone/midbody recruitment), p120-catenin (for spatial RhoA control), and PAK2 (potentially relieving tail-domain autoinhibition); in interphase it localizes to the nucleus via two NLS sequences whose function can be regulated by phosphorylation; KIF23 is also expressed postmitotically in neurons and podocytes to establish nonuniform microtubule polarity required for dendrite and process formation; mutations in KIF23 (e.g., p.P916R) cause cytokinesis failure and congenital dyserythropoietic anemia type III; and its expression is transcriptionally controlled by the p53/p21/DREAM-MMB/CHR axis and by CUX1/E2F1, while post-transcriptionally it is stabilized by NAT10-mediated ac4C mRNA modification and SIRT7-mediated desuccinylation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"KIF23 (MKLP1/CHO1) is a kinesin-6 family motor protein that functions as an essential organizer of the central spindle and midbody during cytokinesis, with additional postmitotic roles in establishing nonuniform microtubule polarity in neurons and podocytes. It forms the centralspindlin heterotetramer with CYK-4/MgcRacGAP, which is necessary and sufficient for antiparallel microtubule bundling [PMID:17942600], and its proper function requires phosphorylation by PLK1 at Ser904/905 [PMID:15199097], Aurora B on C-terminal serines [PMID:15854913], and NDR/LATS kinases at S716/S814 controlling 14-3-3 binding and clustering [PMID:25658096], as well as INCENP-dependent recruitment to the midzone [PMID:15796717] and Arf6 interaction at the midbody via a structurally defined 2:2 heterotetramer that bridges microtubule bundles to membranes [PMID:22522702]. KIF23 transcription is cell-cycle regulated through the p53/p21/DREAM-MMB/CHR axis [PMID:23650552] and CUX1/E2F1 [PMID:19015243], while its mRNA is post-transcriptionally stabilized by NAT10-mediated ac4C modification [PMID:36522719] and its protein by SIRT7-mediated desuccinylation [PMID:38360598]. A missense mutation (p.P916R) in KIF23 causes autosomal dominant congenital dyserythropoietic anemia type III through cytokinesis failure [PMID:23570799].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Identifying PLK1 as a mitotic-phase interactor and kinase for KIF23 established the first regulatory connection between a mitotic kinase and a kinesin motor at the midbody, explaining how cytokinesis-specific motor activation might be achieved.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, and immunofluorescence colocalization in mammalian cells\",\n      \"pmids\": [\"8524282\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific phosphorylation sites not mapped\", \"Functional consequence of PLK1 phosphorylation on cytokinesis not tested\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Demonstrating that KIF23 is expressed postmitotically in neurons and podocytes, and is required for nonuniform microtubule polarity in podocyte processes, revealed a cell-division-independent function for this motor in organizing microtubule arrays for cell morphogenesis.\",\n      \"evidence\": \"Antisense oligonucleotide knockdown in podocytes with hook-decoration MT polarity assay; in situ hybridization and expression analysis in rodent neurons\",\n      \"pmids\": [\"9864367\", \"9749792\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No direct loss-of-function in neurons at this stage\", \"Mechanism by which KIF23 establishes minus-end-distal polarity not defined\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Discovery that GTP-bound Arf proteins directly bind the KIF23 C-terminal tail provided the first link between this motor and membrane trafficking machinery, suggesting a mechanism for coupling microtubule organization to membrane delivery at the cleavage furrow.\",\n      \"evidence\": \"Yeast two-hybrid, GST pull-down with Arf switch-region mutants\",\n      \"pmids\": [\"10506747\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the interaction unknown\", \"In vivo relevance for cytokinesis not tested\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Mapping PLK1 phosphorylation to Ser904/905 and demonstrating that non-phosphorylatable KIF23 causes cytokinesis failure established that PLK1-mediated phosphorylation is functionally required, not merely correlative.\",\n      \"evidence\": \"In vitro kinase assay with phosphosite mutagenesis, siRNA knockdown, rescue experiments in mammalian cells\",\n      \"pmids\": [\"15199097\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether PLK1 phosphorylation regulates motor activity vs. localization vs. protein interactions not distinguished\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identifying Aurora B as a second essential kinase for KIF23 — phosphorylating C-terminal serines required for cytokinesis completion but not midzone localization — separated localization from activation and revealed a two-kinase regulatory logic; simultaneously, INCENP was shown to be required for KIF23 midzone recruitment, defining the recruitment pathway.\",\n      \"evidence\": \"In vitro kinase assay, phosphosite mutagenesis, Aurora kinase inhibitor in C. elegans and human cells; siRNA knockdowns with live-cell imaging and 3D reconstruction\",\n      \"pmids\": [\"15854913\", \"15796717\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Substrates downstream of KIF23 phosphorylation at these sites not identified\", \"How INCENP recruits KIF23 molecularly not resolved\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defining the motor and tail domain requirements for dendritic targeting of KIF23, and identifying two NLS sequences required for interphase nuclear import regulated by phosphorylation, revealed how domain architecture controls both neuronal and cell-cycle-dependent KIF23 trafficking.\",\n      \"evidence\": \"GFP-tagged domain deletion mutants in hippocampal neurons; NLS mutagenesis with cell cycle analysis in mammalian cells\",\n      \"pmids\": [\"16418225\", \"17198681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity of the kinase(s) phosphorylating the NLS in vivo unknown\", \"No loss-of-function phenotype for NLS-deleted KIF23 in neurons\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Biochemical reconstitution of centralspindlin as a CYK-4/KIF23 heterotetramer that is necessary and sufficient for microtubule bundling resolved the stoichiometry and established centralspindlin — not KIF23 alone — as the functional unit for central spindle organization.\",\n      \"evidence\": \"In vitro reconstitution, microtubule bundling assay, conditional genetics and suppressor screen in C. elegans\",\n      \"pmids\": [\"17942600\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"High-resolution structure of the full complex not available\", \"How centralspindlin is targeted specifically to antiparallel overlaps in vivo not resolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrating that CUX1 and E2F1 cooperatively activate the KIF23 promoter upon S-phase entry established the transcriptional basis for cell-cycle-dependent KIF23 expression.\",\n      \"evidence\": \"ChIP, promoter-luciferase assays, overexpression and siRNA of CUX1/E2F1\",\n      \"pmids\": [\"19015243\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether CUX1/E2F1 regulation is sufficient in all cell types not tested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The crystal structure of the Arf6–KIF23 complex as a 2:2 heterotetramer with a membrane-binding β-sheet surface provided a structural mechanism for how the motor bridges microtubule bundles to membranes at the cleavage furrow.\",\n      \"evidence\": \"X-ray crystallography, structure-based mutagenesis, siRNA knockdowns\",\n      \"pmids\": [\"22522702\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Membrane lipid specificity of the complex not defined\", \"How Arf6 activation is spatially coupled to KIF23 localization in vivo not resolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identification of the KIF23 p.P916R mutation as the cause of autosomal dominant CDA III, validated by rescue experiments showing cytokinesis failure, linked the motor's molecular function to human disease and erythropoiesis.\",\n      \"evidence\": \"Targeted sequencing, haplotype analysis in families, RNAi knockdown and mutant rescue in HeLa cells\",\n      \"pmids\": [\"23570799\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural/biochemical mechanism by which P916R disrupts function not determined\", \"No erythroid-specific cellular model used\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrating p53/p21/DREAM-MMB/CHR-dependent transcriptional repression of KIF23 established the tumor suppressor pathway controlling KIF23 expression and explained why KIF23 is upregulated in p53-deficient cancers.\",\n      \"evidence\": \"Promoter reporter assays with CHR mutagenesis, ChIP for DREAM/MMB complexes, qRT-PCR\",\n      \"pmids\": [\"23650552\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relative contributions of DREAM vs. CUX1/E2F1 not integrated\", \"Whether CHR-mediated regulation occurs in non-transformed cells not confirmed\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identifying NDR/LATS kinases as regulators of sequential KIF23 phosphorylation (S716→S814) creating a 14-3-3 binding site revealed a Hippo-pathway-linked mechanism controlling KIF23 clustering during cytokinesis.\",\n      \"evidence\": \"In vitro kinase assays, phosphosite mutagenesis, 14-3-3 binding assays, in vivo phosphorylation analysis\",\n      \"pmids\": [\"25658096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether LATS kinase regulation of KIF23 connects to canonical Hippo pathway tumor suppression not explored\", \"Functional consequence of 14-3-3 binding on motor activity or localization not fully resolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Demonstrating that p120-catenin binds KIF23 at the cleavage furrow to spatially control RhoA cycling connected the adherens junction scaffold to cytokinetic RhoA regulation, explaining how cell-cell adhesion components influence division.\",\n      \"evidence\": \"Reciprocal Co-IP, domain mutagenesis, siRNA knockdown with multinucleation phenotype\",\n      \"pmids\": [\"28004812\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether this mechanism operates in epithelial tissues in vivo not tested\", \"Molecular details of how p120/KIF23 interaction modulates Ect2 or CYK-4 GAP activity unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Discovery that centralspindlin/Ect2 excludes NuMA/dynein from the equatorial membrane revealed a spatial antagonism mechanism by which KIF23-containing complexes define cleavage furrow identity by segregating cortical force generators.\",\n      \"evidence\": \"siRNA knockdowns, immunofluorescence of membrane domain compartmentalization, live-cell imaging\",\n      \"pmids\": [\"36197340\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Biochemical basis for mutual exclusion between centralspindlin/Ect2 and NuMA/dynein complexes not defined\", \"Whether this mechanism operates in asymmetric divisions not tested\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Post-transcriptional regulation of KIF23 by NAT10-mediated ac4C mRNA modification and transcriptional activation by FOXM1 or TAZ-TEAD2 revealed multiple cancer-relevant pathways converging to elevate KIF23 expression.\",\n      \"evidence\": \"RIP-seq and acRIP-seq for NAT10/ac4C; ChIP for FOXM1 at KIF23 promoter; CRISPRi screen identifying KIF23 as TAZ-TEAD2 target\",\n      \"pmids\": [\"36522719\", \"36940637\", \"36894036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether these regulatory pathways operate independently or synergistically not determined\", \"Relative contribution of transcriptional vs. post-transcriptional regulation to KIF23 protein levels in normal cells unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"KIF23 depletion in mouse cortex disrupted spindle orientation and apical junction integrity in neural stem cells — rescued by wild-type but not a microcephaly variant — establishing KIF23 as required for cortical neurogenesis beyond its canonical cytokinesis role.\",\n      \"evidence\": \"In vivo knockdown in mouse cortex, rescue with WT vs. disease-variant human KIF23, live imaging, immunofluorescence\",\n      \"pmids\": [\"39632980\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether spindle orientation defect is independent of the cytokinesis role not fully separated\", \"Identity and mechanism of the microcephaly-associated variant not fully characterized\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism by which KIF23 motor activity is autoinhibited and relieved in vivo, the structural basis of full-length centralspindlin, and how KIF23's multiple post-translational modifications are integrated to coordinate cytokinesis progression remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structure of full-length centralspindlin or autoinhibited KIF23\", \"Integration of PLK1, Aurora B, and LATS phosphorylation events temporally and functionally not resolved\", \"Autoinhibition mechanism rests on a retracted paper (PMID:33204722) and awaits independent confirmation\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [6, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 3, 6]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 2, 3, 6, 13, 14]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [18, 21, 24]}\n    ],\n    \"complexes\": [\n      \"centralspindlin (CYK-4/MKLP1 heterotetramer)\"\n    ],\n    \"partners\": [\n      \"RACGAP1\",\n      \"PLK1\",\n      \"ARF6\",\n      \"INCENP\",\n      \"CTNND1\",\n      \"AURKB\",\n      \"MYH9\",\n      \"SIRT7\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}