| 1995 |
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. |
Co-immunoprecipitation, co-localization by immunofluorescence, in vitro kinase assay |
Molecular and cellular biology |
Medium |
8524282
|
| 2004 |
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. |
Transient transfection, domain-deletion analysis, vector-based RNAi, site-directed mutagenesis, rescue experiments |
Journal of cell science |
High |
15199097
|
| 2005 |
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. |
In vitro kinase assay, in vivo phosphorylation (C. elegans and human cells), phospho-mutant analysis, aurora kinase inhibitor treatment |
Current biology : CB |
High |
15854913
|
| 2005 |
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. |
RNAi/siRNA knockdown, immunofluorescence, 3D live-cell imaging reconstruction |
The Biochemical journal |
Medium |
15796717
|
| 2007 |
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. |
Biochemical reconstitution, in vitro microtubule bundling assay, genetic epistasis (suppressor screen with second-site mutations), co-immunoprecipitation |
Molecular biology of the cell |
High |
17942600
|
| 1999 |
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. |
Yeast two-hybrid screen, GST pulldown assay, deletion mapping, Arf3 point-mutation screen |
Cell motility and the cytoskeleton |
Medium |
10506747
|
| 2012 |
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. |
Crystal structure determination, structure-based mutagenesis, siRNA knockdown, live-cell imaging |
The EMBO journal |
High |
22522702
|
| 2013 |
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. |
siRNA depletion, ubiquitination assay, co-immunoprecipitation, immunofluorescence |
Autophagy |
Medium |
24128730
|
| 2013 |
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. |
Next-generation resequencing, haplotype analysis, RNAi knockdown and rescue in HeLa cells, functional cytokinesis assay |
Blood |
High |
23570799
|
| 1998 |
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. |
Antisense oligonucleotide treatment, hook-decoration of microtubules (polarity assay), taxol/nocodazole recovery experiments, immunolocalization |
The Journal of cell biology |
Medium |
9864367
|
| 1998 |
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. |
In situ hybridization (rodent brain sections), mRNA expression analysis in cultured neurons |
The European journal of neuroscience |
Low |
9749792
|
| 2004 |
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. |
Genetic mutant analysis, immunofluorescence of polarity markers, confocal microscopy in C. elegans |
Current biology : CB |
Medium |
15182666
|
| 2006 |
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. |
Deletion/mutation mapping, ectopic expression, fluorescence microscopy, cell cycle analysis |
Biochemical and biophysical research communications |
Medium |
17198681
|
| 1999 |
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. |
GFP-fusion expression in HeLa cells, subcellular fractionation, fluorescence microscopy |
Biochemical and biophysical research communications |
Low |
10403813
|
| 2006 |
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. |
GFP-tagged domain deletion constructs expressed in primary hippocampal neurons, fluorescence microscopy |
Journal of cell science |
Medium |
16418225
|
| 2013 |
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. |
Promoter-reporter assays, chromatin immunoprecipitation (DREAM/MMB binding to CHR), siRNA knockdown of p21, RT-PCR and western blot |
PloS one |
Medium |
23650552
|
| 2008 |
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. |
Chromatin immunoprecipitation, promoter-luciferase reporter assays, siRNA knockdown, overexpression |
Molecular and cellular biology |
Medium |
19015243
|
| 2015 |
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. |
In vitro kinase assay, site-directed mutagenesis, in vivo phosphorylation assay, 14-3-3 binding assay |
PloS one |
Medium |
25658096
|
| 2016 |
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. |
Genetic epistasis (Drosophila pathway mutants), genetic suppression, in vivo imaging of MT dynamics, overexpression of Pav-KLP |
The Journal of cell biology |
Medium |
27502486
|
| 2013 |
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. |
Inducible v-Src expression, flow cytometry, time-lapse microscopy, immunofluorescence localization |
Experimental cell research |
Medium |
23562843
|
| 2016 |
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. |
Co-immunoprecipitation, immunofluorescence (cleavage furrow enrichment), domain deletion analysis, siRNA knockdown |
Nature communications |
Medium |
28004812
|
| 2020 |
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. |
GST pulldown followed by LC-MS/MS, co-immunoprecipitation, FRET, siRNA knockdown, overexpression |
BioMed research international |
Low |
33204722 38550036
|
| 2022 |
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. |
siRNA depletion, live-cell imaging (membrane compartmentalization), immunofluorescence |
The Journal of cell biology |
Medium |
36197340
|
| 2020 |
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. |
Co-immunoprecipitation, immunofluorescence (subcellular localization of Amer1), functional rescue experiments, western blot |
Aging |
Medium |
32365332
|
| 2024 |
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. |
Co-immunoprecipitation, western blot for succinylation, overexpression/silencing in HEK-293T and ATC cells, cell viability/migration assays |
BMC cancer |
Medium |
38360598
|
| 2023 |
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. |
ChIP for RNA pol II and H3K27ac at KIF23 promoter, siRNA knockdown, western blot, drug resistance assays |
Biochemical and biophysical research communications |
Medium |
36940637
|
| 2024 |
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. |
In utero electroporation knockdown in mice, immunofluorescence, live imaging, rescue with wild-type vs. variant human KIF23 |
The EMBO journal |
High |
39632980
|
| 2002 |
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. |
GFP-tagging and live imaging in zebrafish embryos, dominant-negative mRNA injection, fractionation |
Physiological genomics |
Medium |
11842131
|
| 2022 |
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. |
RIP-seq, acRIP-seq, RNA immunoprecipitation, luciferase reporter assay, siRNA knockdown, xenograft models |
Journal of experimental & clinical cancer research : CR |
Medium |
36522719
|
| 2019 |
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. |
MLN4924 drug treatment in synchronized cells, fixed and live-cell microscopy, immunofluorescence |
Cell cycle (Georgetown, Tex.) |
Low |
31057046
|
| 2026 |
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. |
Co-immunoprecipitation, protein half-life assays, ubiquitination assays, CRISPR/Cas9 knockout, site-directed mutagenesis |
Clinical and translational medicine |
Medium |
41940421
|
| 2025 |
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. |
Proteomic profiling of knockdown vs. overexpression fibroblasts, adeno-associated virus shRNA knockdown in vivo, western blot, lipid droplet analysis, echocardiography |
Hypertension |
Medium |
41078122
|
| 2025 |
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. |
Chromatin immunoprecipitation (ETV5 binding to KIF23 promoter), AAV9-mediated overexpression/knockdown in mice, western blot, cognitive behavior assays |
Biochemical pharmacology |
Medium |
40983152
|
| 2021 |
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. |
Co-immunoprecipitation (domain mapping), siRNA knockdown, overexpression, drug sensitivity assays |
Head & neck |
Low |
34918847
|
| 2025 |
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. |
In vitro kinase assay, phospho-mutant analysis, co-immunoprecipitation, live-cell imaging |
bioRxivpreprint |
Low |
|