KIF23

The human KIF23 gene is located on chromosome 15 at band q23 and spans 25 exons. It encodes a member of the kinesin family of motor proteins, which are essential for processes such as cytokinesis. The KIF23 gene undergoes alternative splicing, resulting in at least two transcript variants that produce different protein isoforms, most notably the larger CHO1 and the smaller MKLP1.

KIF23 is a member of the kinesin superfamily of microtubule-dependent motor proteins. Structurally, KIF23 consists of several distinct domains: a conserved N-terminal kinesin motor domain responsible for ATP hydrolysis and microtubule binding, a central coiled-coil region that mediates dimerization and interaction with partner proteins, and a C-terminal tail domain, which includes the Arf6-interacting domain important for regulatory functions.{{cite web | title = Kinesin family member 23 | url = https://zfin.org/ZDB-GENE-991019-4 | work = Zebrafish Information Network (ZFIN) }} The protein exists as part of a heterotetrameric complex called centralspindlin, composed of two KIF23 molecules and two RACGAP1 molecules.{{cite thesis | vauthors = Vikberg AL | title = Mitotic Kinesin-Like Protein 1 (MKLP1/KIF23) in hereditary congenital dyserythropoietic anemia type III and in cancer | date = 2021 | degree = PhD. | publisher = Umeå Universitet | url = https://umu.diva-portal.org/smash/get/diva2:1527301/FULLTEXT02.pdf }}{{cite web | title = KIF23 | url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIF23 | work = GeneCards }} This complex localizes to the central spindle during anaphase and the midbody during cytokinesis, where it orchestrates the assembly of the contractile ring and abscission machinery necessary for cell division.{{cite web | title = KIF23_HUMAN | work = UniProt | url = https://www.uniprot.org/uniprotkb/Q02241/entry | id = Q02241 }} KIF23 is subject to alternative splicing, resulting in at least two isoforms: the larger CHO1 and the smaller MKLP1. The protein’s structure enables it to cross-bridge antiparallel microtubules and facilitate their movement, a function essential for both mitotic spindle organization and successful cytokinesis.

File:Kinesin-6 and Kinesin-12.jpg

KIF23 (also known as Kinesin-6, CHO1/MKLP1, C. elegans ZEN-4 and Drosophila Pavarotti) is a member of kinesin-like protein family. This family includes microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. This protein has been shown to cross-bridge antiparallel microtubules and drive microtubule movement in vitro. Alternate splicing of this gene results in two transcript variants encoding two different isoforms, better known as CHO1, the larger isoform and MKLP1, the smaller isoform. KIF23 is a plus-end directed motor protein expressed in mitosis, involved in the formation of the cleavage furrow in late anaphase and in cytokinesis.{{cite journal | vauthors = Hutterer A, Glotzer M, Mishima M | title = Clustering of centralspindlin is essential for its accumulation to the central spindle and the midbody | journal = Current Biology | volume = 19 | issue = 23 | pages = 2043–2049 | date = December 2009 | pmid = 19962307 | pmc = 3349232 | doi = 10.1016/j.cub.2009.10.050 | bibcode = 2009CBio...19.2043H }}{{cite journal | vauthors = Hornick JE, Karanjeet K, Collins ES, Hinchcliffe EH | title = Kinesins to the core: The role of microtubule-based motor proteins in building the mitotic spindle midzone | journal = Seminars in Cell & Developmental Biology | volume = 21 | issue = 3 | pages = 290–299 | date = May 2010 | pmid = 20109573 | pmc = 3951275 | doi = 10.1016/j.semcdb.2010.01.017 }} KIF23 is part of the centralspindlin complex that includes PRC1, Aurora B and 14-3-3 which cluster together at the spindle midzone to enable anaphase in dividing cells.{{cite journal | vauthors = Neef R, Klein UR, Kopajtich R, Barr FA | title = Cooperation between mitotic kinesins controls the late stages of cytokinesis | journal = Current Biology | volume = 16 | issue = 3 | pages = 301–307 | date = February 2006 | pmid = 16461284 | doi = 10.1016/j.cub.2005.12.030 | doi-access = free | bibcode = 2006CBio...16..301N }}{{cite journal | vauthors = Douglas ME, Davies T, Joseph N, Mishima M | title = Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis | journal = Current Biology | volume = 20 | issue = 10 | pages = 927–933 | date = May 2010 | pmid = 20451386 | pmc = 3348768 | doi = 10.1016/j.cub.2010.03.055 | bibcode = 2010CBio...20..927D }}{{cite journal | vauthors = Glotzer M | title = The 3Ms of central spindle assembly: microtubules, motors and MAPs | journal = Nature Reviews. Molecular Cell Biology | volume = 10 | issue = 1 | pages = 9–20 | date = January 2009 | pmid = 19197328 | pmc = 2789570 | doi = 10.1038/nrm2609 }}

In neuronal development KIF23 is involved in the transport of minus-end distal microtubules into dendrites and is expressed exclusively in cell bodies and dendrites.{{cite journal | vauthors = Sharp DJ, Kuriyama R, Essner R, Baas PW | title = Expression of a minus-end-directed motor protein induces Sf9 cells to form axon-like processes with uniform microtubule polarity orientation | journal = Journal of Cell Science | volume = 110 | issue = 19 | pages = 2373–2380 | date = October 1997 | pmid = 9410876 | doi = 10.1242/jcs.110.19.2373 }}{{cite journal | vauthors = Sharp DJ, Yu W, Ferhat L, Kuriyama R, Rueger DC, Baas PW | title = Identification of a microtubule-associated motor protein essential for dendritic differentiation | journal = The Journal of Cell Biology | volume = 138 | issue = 4 | pages = 833–843 | date = August 1997 | pmid = 9265650 | pmc = 2138050 | doi = 10.1083/jcb.138.4.833 }}{{cite journal | vauthors = Yu W, Sharp DJ, Kuriyama R, Mallik P, Baas PW | title = Inhibition of a mitotic motor compromises the formation of dendrite-like processes from neuroblastoma cells | journal = The Journal of Cell Biology | volume = 136 | issue = 3 | pages = 659–668 | date = February 1997 | pmid = 9024695 | pmc = 2134303 | doi = 10.1083/jcb.136.3.659 }}{{cite journal | vauthors = Yu W, Cook C, Sauter C, Kuriyama R, Kaplan PL, Baas PW | title = Depletion of a microtubule-associated motor protein induces the loss of dendritic identity | journal = The Journal of Neuroscience| volume = 20 | issue = 15 | pages = 5782–5791 | date = August 2000 | pmid = 10908619 | pmc = 6772545 | doi = 10.1523/JNEUROSCI.20-15-05782.2000 }}{{cite journal | vauthors = Xu X, He C, Zhang Z, Chen Y | title = MKLP1 requires specific domains for its dendritic targeting | journal = Journal of Cell Science | volume = 119 | issue = Pt 3 | pages = 452–458 | date = February 2006 | pmid = 16418225 | doi = 10.1242/jcs.02750 | s2cid = 29919060 }} Knockdown of KIF23 by antisense oligonucleotides and by siRNA both cause a significant increase in axon length and a decrease in dendritic phenotype in neuroblastoma cells and in rat neurons.{{cite journal | vauthors = Lin S, Liu M, Mozgova OI, Yu W, Baas PW | title = Mitotic motors coregulate microtubule patterns in axons and dendrites | journal = The Journal of Neuroscience| volume = 32 | issue = 40 | pages = 14033–14049 | date = October 2012 | pmid = 23035110 | pmc = 3482493 | doi = 10.1523/JNEUROSCI.3070-12.2012 }} In differentiating neurons, KIF23 restricts the movement of short microtubules into axons by acting as a "brake" against the driving forces of cytoplasmic dynein. As neurons mature, KIF23 drives minus-end distal microtubules into nascent dendrites contributing to the multi-polar orientation of dendritic microtubules and the formation of their short, fat, tapering morphology.

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Mutations in KIF23 have been associated with Congenital dyserythropoietic anemia type III, highlighting its importance in normal cell function and development.{{cite journal | vauthors = Matuliene J, Kuriyama R | title = Kinesin-like protein CHO1 is required for the formation of midbody matrix and the completion of cytokinesis in mammalian cells | journal = Molecular Biology of the Cell | volume = 13 | issue = 6 | pages = 1832–45 | date = June 2002 | pmid = 12058052 | pmc = 117607 | doi = 10.1091/mbc.01-10-0504 }}{{cite journal | vauthors = Gruneberg U, Neef R, Li X, Chan EH, Chalamalasetty RB, Nigg EA, Barr FA | title = KIF14 and citron kinase act together to promote efficient cytokinesis | journal = The Journal of Cell Biology | volume = 172 | issue = 3 | pages = 363–72 | date = January 2006 | pmid = 16431929 | pmc = 2063646 | doi = 10.1083/jcb.200511061 | url = }}

KIF23 has also been implicated in the formation and proliferation of GL261 gliomas in mouse.{{cite journal | vauthors = Takahashi S, Fusaki N, Ohta S, Iwahori Y, Iizuka Y, Inagawa K, Kawakami Y, Yoshida K, Toda M | title = Downregulation of KIF23 suppresses glioma proliferation | journal = Journal of Neuro-Oncology | volume = 106 | issue = 3 | pages = 519–529 | date = February 2012 | pmid = 21904957 | doi = 10.1007/s11060-011-0706-2 | s2cid = 33089132 }}

KIF23 has been shown to interact with:

• ARF3,{{cite journal | vauthors = Boman AL, Kuai J, Zhu X, Chen J, Kuriyama R, Kahn RA | title = Arf proteins bind to mitotic kinesin-like protein 1 (MKLP1) in a GTP-dependent fashion | journal = Cell Motility and the Cytoskeleton | volume = 44 | issue = 2 | pages = 119–132 | date = October 1999 | pmid = 10506747 | doi = 10.1002/(SICI)1097-0169(199910)44:2<119::AID-CM4>3.0.CO;2-C }}
• AURKB,{{cite journal | vauthors = Guse A, Mishima M, Glotzer M | title = Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis | journal = Current Biology | volume = 15 | issue = 8 | pages = 778–786 | date = April 2005 | pmid = 15854913 | doi = 10.1016/j.cub.2005.03.041 | doi-access = free | bibcode = 2005CBio...15..778G }}{{cite journal | vauthors = Li J, Wang J, Jiao H, Liao J, Xu X | title = Cytokinesis and cancer: Polo loves ROCK'n' Rho(A) | journal = Journal of Genetics and Genomics = Yi Chuan Xue Bao | volume = 37 | issue = 3 | pages = 159–172 | date = March 2010 | pmid = 20347825 | doi = 10.1016/S1673-8527(09)60034-5 | url = https://zenodo.org/record/890333 }}
• BIRC6,{{cite journal | vauthors = Pohl C, Jentsch S | title = Final stages of cytokinesis and midbody ring formation are controlled by BRUCE | journal = Cell | volume = 132 | issue = 5 | pages = 832–845 | date = March 2008 | pmid = 18329369 | doi = 10.1016/j.cell.2008.01.012 | doi-access = free }} and
• PRC1.{{cite journal | vauthors = Kurasawa Y, Earnshaw WC, Mochizuki Y, Dohmae N, Todokoro K | title = Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation | journal = The EMBO Journal | volume = 23 | issue = 16 | pages = 3237–3248 | date = August 2004 | pmid = 15297875 | pmc = 514520 | doi = 10.1038/sj.emboj.7600347 }}

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