Disease relevance of KIF23

• Microinjection of CHO1, either as an ascites fluid or as purified IgM, results in mitotic inhibition in a stage-specific and dose-dependent manner [1].

High impact information on KIF23

• Instead, daughter cells remain connected by intercellular bridges that contain bundled microtubules and cytoplasmic organelles but exclude normal midbody components such as MKLP1 and Aurora B [2].
• Annexin 11 is recruited to the midbody in late telophase, where it forms part of the detergent-resistant matrix that also contains CHO1 [2].
• Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis [3].
• CHO1 is a kinesin-like protein of the mitotic kinesin-like protein (MKLP)1 subfamily present in central spindles and midbodies in mammalian cells [4].
• (c) Treatment of differentiating podocytes with CHO1/MKLP1 antisense oligonucleotides abolished the formation of processes and the nonuniform polarity of MTs [5].

Biological context of KIF23

• Overexpression of a non-Plk1-phosphorylatable CHO1 mutant caused cytokinesis defects, presumably because of dominant negative effect of the construct [6].
• Using the vector-based RNA interference approach, we showed that depletion of CHO1/MKLP-1 causes the formation of multinucleate cells with more centrosomes, probably because of a defect in the early phase of cytokinesis [6].
• Eleven independent isolates contained plasmids encoding the C-terminal tail of mitotic kinesin-like protein-1 (MKLP1) [7].
• A screen for mutations in Arf3 that specifically lost the ability to bind MKLP1 identified 10 of 14 point mutations in the GTP-sensitive switch I or switch II regions of Arf3 [7].
• The MKLP1 (mitotic kinesin-like protein) is a component of centralspindlin complex that has been implicated in assembly of midzone/midbody during mitosis and is essential for cytokinesis [8].

Anatomical context of KIF23

• Although relaxing furrows contained overlapping microtubules from opposing centrosomes, they lacked microtubule bundles as well as INCENP and CHO1 [9].
• A monoclonal antibody raised against mitotic spindles isolated from CHO cells ([CHO1], Sellitto, C., and R. Kuriyama. 1988. J. Cell Biol. 106:431-439) identifies an epitope that resides on polypeptides of 95 and 105 kD and is localized in the spindles of diverse organisms [1].
• The CHO1 antigen in HeLa cell extracts copurifies with taxol-stabilized microtubules [1].
• Thus, this CHO1/MKLP1 fragment establishes a nonuniform MT polarity pattern and does so by a similar sequence of events as occurs with the dendrite, the antecedent of which is a short process with a uniform MT polarity orientation [10].
• Through the use of a series of degenerate primers selected from consensus sequences of CHO-1 and CHT1, we generated two probes that were used to search a Limulus cDNA library produced from central nervous system (CNS) tissue [11].

Associations of KIF23 with chemical compounds

• Here, we show that in C. elegans embryos and in cultured human cells, respectively, ZEN-4 and MKLP1 are phosphorylated by aurora B in vitro and in vivo on conserved C-terminal serine residues [12].
• The diffusion coefficient and sedimentation coefficient were determined for the native CHO1 antigen by gel filtration and sucrose density gradient centrifugation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[13]
• (2000. Nature Neurosci. 3, 120-125) recently reported the successful cloning of the choline co-transporter in Caenorhabditis elegans (CHO-1) and rat (CHT1) [11].
• Performance time, running speed, blood glucose and blood lactate concentrations were evaluated during two 25-km treadmill time trial (trial 1 and trial 2) separated by 7 days in which two groups (CHO1 and CHO2) had a carbohydrate loading [14].

Physical interactions of KIF23

• Further deletion mapping allowed the identification of an 88 amino acid Arf3 binding domain in the C-terminus of MKLP1 [7].
• Cep55 directly binds to MKLP1 in vitro and associates with the MKLP1-MgcRacGAP centralspindlin complex in vivo [15].

Enzymatic interactions of KIF23

• The mitotic kinase Cdk1/cyclin B phosphorylates the motor domain of ZEN-4 on a conserved site within a basic amino-terminal extension characteristic of the MKLP1 subfamily [16].

Other interactions of KIF23

• Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1 [6].
• Furthermore, we show that INCENP is required for recruiting MKLP1 to the spindle midzone/midbody [8].
• An analogous complex, containing equimolar amounts of a CYK-4 ortholog and MKLP-1, was purified from mammalian cells [17].
• These data indicate a conserved role for aurora-B-mediated phosphorylation of ZEN-4/MKLP1 in the completion of cytokinesis [12].
• Cleavage furrows formed between centrosomes lacking an intervening spindle and chromosomes contain microtubule bundles, INCENP, and CHO1 but not CENP-E [9].

Analytical, diagnostic and therapeutic context of KIF23

• Two-hybrid assays of the C-terminal domain of MKLP1 with each of the human Arf isoforms revealed strong interaction with each [7].
• These results demonstrate that CHO1 consists of functionally differentiated subregions that act in concert to ensure complete cell separation [18].
• Immunofluorescence analysis of injected cells reveals that those which complete mitosis display normal localization of CHO1, whereas arrested cells show no specific localization of the CHO1 antigen within the spindle [1].

References