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.[2] 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.[1][3][4] 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.[5][6][7]
In neurons
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.[8][9][10][11][12] 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.[10][11][13] 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.[13]
KIF23 has been implicated in the formation and proliferation of GL261gliomas in mouse.[19]
References
↑ 1.01.1Nislow C, Lombillo VA, Kuriyama R, McIntosh JR (Nov 1992). "A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles". Nature. 359 (6395): 543–7. doi:10.1038/359543a0. PMID1406973.
↑Hornick JE, Karanjeet K, Collins ES, Hinchcliffe EH (May 2010). "Kinesins to the core: The role of microtubule-based motor proteins in building the mitotic spindle midzone". Semin. Cell Dev. Biol. 21 (3): 290–9. doi:10.1016/j.semcdb.2010.01.017. PMID20109573.
↑Neef R, Klein UR, Kopajtich R, Barr FA (February 2006). "Cooperation between mitotic kinesins controls the late stages of cytokinesis". Curr. Biol. 16 (3): 301–7. doi:10.1016/j.cub.2005.12.030. PMID16461284.
↑Sharp DJ, Kuriyama R, Essner R, Baas PW (October 1997). "Expression of a minus-end-directed motor protein induces Sf9 cells to form axon-like processes with uniform microtubule polarity orientation". J. Cell Sci. 110 (19): 2373–80. PMID9410876.
↑ 11.011.1Yu W, Cook C, Sauter C, Kuriyama R, Kaplan PL, Baas PW (August 2000). "Depletion of a microtubule-associated motor protein induces the loss of dendritic identity". J. Neurosci. 20 (15): 5782–91. PMID10908619.
↑Xu X, He C, Zhang Z, Chen Y (February 2006). "MKLP1 requires specific domains for its dendritic targeting". J. Cell Sci. 119 (Pt 3): 452–8. doi:10.1242/jcs.02750. PMID16418225.
↑Guse A, Mishima M, Glotzer M (April 2005). "Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis". Curr. Biol. 15 (8): 778–86. doi:10.1016/j.cub.2005.03.041. PMID15854913.
↑Li J, Wang J, Jiao H, Liao J, Xu X (March 2010). "Cytokinesis and cancer: Polo loves ROCK'n' Rho(A)". J Genet Genomics. 37 (3): 159–72. doi:10.1016/S1673-8527(09)60034-5. PMID20347825.
↑Pohl C, Jentsch S (March 2008). "Final stages of cytokinesis and midbody ring formation are controlled by BRUCE". Cell. 132 (5): 832–45. doi:10.1016/j.cell.2008.01.012. PMID18329369.
↑Takahashi S, Fusaki N, Ohta S, Iwahori Y, Iizuka Y, Inagawa K, Kawakami Y, Yoshida K, Toda M (February 2012). "Downregulation of KIF23 suppresses glioma proliferation". J. Neurooncol. 106 (3): 519–29. doi:10.1007/s11060-011-0706-2. PMID21904957.
Deavours BE, Walker RA (July 1999). "Nuclear localization of C-terminal domains of the kinesin-like protein MKLP-1". Biochem. Biophys. Res. Commun. 260 (3): 605–8. doi:10.1006/bbrc.1999.0952. PMID10403813.
Mishima M, Kaitna S, Glotzer M (January 2002). "Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity". Dev. Cell. 2 (1): 41–54. doi:10.1016/S1534-5807(01)00110-1. PMID11782313.
Kitamura T, Kawashima T, Minoshima Y, Tonozuka Y, Hirose K, Nosaka T (December 2001). "Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation". Cell Struct. Funct. 26 (6): 645–51. doi:10.1247/csf.26.645. PMID11942621.
Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (February 2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase". Genes Cells. 9 (2): 105–20. doi:10.1111/j.1365-2443.2004.00705.x. PMID15009096.
Liu X, Zhou T, Kuriyama R, Erikson RL (July 2004). "Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1". J. Cell Sci. 117 (Pt 15): 3233–46. doi:10.1242/jcs.01173. PMID15199097.
Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T (August 2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID15324660.
Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (January 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID15592455.
Benzinger A, Muster N, Koch HB, Yates JR, Hermeking H (June 2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Mol. Cell. Proteomics. 4 (6): 785–95. doi:10.1074/mcp.M500021-MCP200. PMID15778465.