Abstract
Microtubule-associated mechanoenzymes have been proposed to play a fundamental role in chromosome movement. We have cloned and characterized the cDNA for a novel protein, named Chromokinesin, that fulfills several of the criteria expected of a mitotic motor. Chromokinesin contains both a kinesin motor-like domain and an unusual basic-leucine zipper DNA-binding domain. Its mRNA is readily detectable in proliferating cells, but not in postmitotic cells. Immunocytochemical analysis with antibodies directed against the nonconserved COOH-terminal region of Chromokinesin indicates that the protein is localized in the nucleus, and primarily associated with chromosome arms in mitotic cells. These data suggest that Chromokinesin is likely to function as a microtubule-based mitotic motor with DNA as its cargo.
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- Ault J. G., DeMarco A. J., Salmon E. D., Rieder C. L. Studies on the ejection properties of asters: astral microtubule turnover influences the oscillatory behavior and positioning of mono-oriented chromosomes. J Cell Sci. 1991 Aug;99(Pt 4):701–710. doi: 10.1242/jcs.99.4.701. [DOI] [PubMed] [Google Scholar]
- Biffo S., Verdun di Cantogno L., Fasolo A. Double labeling with non-isotopic in situ hybridization and BrdU immunohistochemistry: calmodulin (CaM) mRNA expression in post-mitotic neurons of the olfactory system. J Histochem Cytochem. 1992 Apr;40(4):535–540. doi: 10.1177/40.4.1552187. [DOI] [PubMed] [Google Scholar]
- Bloom K. The centromere frontier: kinetochore components, microtubule-based motility, and the CEN-value paradox. Cell. 1993 May 21;73(4):621–624. doi: 10.1016/0092-8674(93)90242-i. [DOI] [PubMed] [Google Scholar]
- Carlson J. G. Mitotic Behavior of Induced Chromosomal Fragments Lacking Spindle Attachments in the Neuroblasts of the Grasshopper. Proc Natl Acad Sci U S A. 1938 Nov;24(11):500–507. doi: 10.1073/pnas.24.11.500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coue M., Lombillo V. A., McIntosh J. R. Microtubule depolymerization promotes particle and chromosome movement in vitro. J Cell Biol. 1991 Mar;112(6):1165–1175. doi: 10.1083/jcb.112.6.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Earnshaw W. C., Ratrie H., 3rd, Stetten G. Visualization of centromere proteins CENP-B and CENP-C on a stable dicentric chromosome in cytological spreads. Chromosoma. 1989 Jun;98(1):1–12. doi: 10.1007/BF00293329. [DOI] [PubMed] [Google Scholar]
- Endow S. A., Henikoff S., Soler-Niedziela L. Mediation of meiotic and early mitotic chromosome segregation in Drosophila by a protein related to kinesin. Nature. 1990 May 3;345(6270):81–83. doi: 10.1038/345081a0. [DOI] [PubMed] [Google Scholar]
- Endow S. A. The emerging kinesin family of microtubule motor proteins. Trends Biochem Sci. 1991 Jun;16(6):221–225. doi: 10.1016/0968-0004(91)90089-e. [DOI] [PubMed] [Google Scholar]
- Enos A. P., Morris N. R. Mutation of a gene that encodes a kinesin-like protein blocks nuclear division in A. nidulans. Cell. 1990 Mar 23;60(6):1019–1027. doi: 10.1016/0092-8674(90)90350-n. [DOI] [PubMed] [Google Scholar]
- Goldstein L. S. The kinesin superfamily: tails of functional redundancy. Trends Cell Biol. 1991 Oct;1(4):93–98. doi: 10.1016/0962-8924(91)90036-9. [DOI] [PubMed] [Google Scholar]
- Gorbsky G. J., Sammak P. J., Borisy G. G. Chromosomes move poleward in anaphase along stationary microtubules that coordinately disassemble from their kinetochore ends. J Cell Biol. 1987 Jan;104(1):9–18. doi: 10.1083/jcb.104.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hershko A., Ciechanover A. The ubiquitin system for protein degradation. Annu Rev Biochem. 1992;61:761–807. doi: 10.1146/annurev.bi.61.070192.003553. [DOI] [PubMed] [Google Scholar]
- Holloway S. L., Glotzer M., King R. W., Murray A. W. Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell. 1993 Jul 2;73(7):1393–1402. doi: 10.1016/0092-8674(93)90364-v. [DOI] [PubMed] [Google Scholar]
- Hyman A. A., Middleton K., Centola M., Mitchison T. J., Carbon J. Microtubule-motor activity of a yeast centromere-binding protein complex. Nature. 1992 Oct 8;359(6395):533–536. doi: 10.1038/359533a0. [DOI] [PubMed] [Google Scholar]
- Koshland D. Mitosis: back to the basics. Cell. 1994 Jul 1;77(7):951–954. doi: 10.1016/0092-8674(94)90432-4. [DOI] [PubMed] [Google Scholar]
- Kosik K. S., Orecchio L. D., Schnapp B., Inouye H., Neve R. L. The primary structure and analysis of the squid kinesin heavy chain. J Biol Chem. 1990 Feb 25;265(6):3278–3283. [PubMed] [Google Scholar]
- Kouzarides T., Ziff E. The role of the leucine zipper in the fos-jun interaction. Nature. 1988 Dec 15;336(6200):646–651. doi: 10.1038/336646a0. [DOI] [PubMed] [Google Scholar]
- Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
- Leslie R. J. Chromosomes attain a metaphase position on half-spindles in the absence of an opposing spindle pole. J Cell Sci. 1992 Sep;103(Pt 1):125–130. doi: 10.1242/jcs.103.1.125. [DOI] [PubMed] [Google Scholar]
- Liao H., Li G., Yen T. J. Mitotic regulation of microtubule cross-linking activity of CENP-E kinetochore protein. Science. 1994 Jul 15;265(5170):394–398. doi: 10.1126/science.8023161. [DOI] [PubMed] [Google Scholar]
- McDonald H. B., Stewart R. J., Goldstein L. S. The kinesin-like ncd protein of Drosophila is a minus end-directed microtubule motor. Cell. 1990 Dec 21;63(6):1159–1165. doi: 10.1016/0092-8674(90)90412-8. [DOI] [PubMed] [Google Scholar]
- McIntosh J. R., Pfarr C. M. Mitotic motors. J Cell Biol. 1991 Nov;115(3):577–585. doi: 10.1083/jcb.115.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McNeill P. A., Berns M. W. Chromosome behavior after laser microirradiation of a single kinetochore in mitotic PtK2 cells. J Cell Biol. 1981 Mar;88(3):543–553. doi: 10.1083/jcb.88.3.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meluh P. B., Rose M. D. KAR3, a kinesin-related gene required for yeast nuclear fusion. Cell. 1990 Mar 23;60(6):1029–1041. doi: 10.1016/0092-8674(90)90351-e. [DOI] [PubMed] [Google Scholar]
- Niclas J., Navone F., Hom-Booher N., Vale R. D. Cloning and localization of a conventional kinesin motor expressed exclusively in neurons. Neuron. 1994 May;12(5):1059–1072. doi: 10.1016/0896-6273(94)90314-x. [DOI] [PubMed] [Google Scholar]
- Pfarr C. M., Coue M., Grissom P. M., Hays T. S., Porter M. E., McIntosh J. R. Cytoplasmic dynein is localized to kinetochores during mitosis. Nature. 1990 May 17;345(6272):263–265. doi: 10.1038/345263a0. [DOI] [PubMed] [Google Scholar]
- Rieder C. L., Davison E. A., Jensen L. C., Cassimeris L., Salmon E. D. Oscillatory movements of monooriented chromosomes and their position relative to the spindle pole result from the ejection properties of the aster and half-spindle. J Cell Biol. 1986 Aug;103(2):581–591. doi: 10.1083/jcb.103.2.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rieder C. L., Salmon E. D. Motile kinetochores and polar ejection forces dictate chromosome position on the vertebrate mitotic spindle. J Cell Biol. 1994 Feb;124(3):223–233. doi: 10.1083/jcb.124.3.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
- Saxton W. M., Hicks J., Goldstein L. S., Raff E. C. Kinesin heavy chain is essential for viability and neuromuscular functions in Drosophila, but mutants show no defects in mitosis. Cell. 1991 Mar 22;64(6):1093–1102. doi: 10.1016/0092-8674(91)90264-y. [DOI] [PubMed] [Google Scholar]
- Scholey J. M., Heuser J., Yang J. T., Goldstein L. S. Identification of globular mechanochemical heads of kinesin. Nature. 1989 Mar 23;338(6213):355–357. doi: 10.1038/338355a0. [DOI] [PubMed] [Google Scholar]
- Skoufias D. A., Scholey J. M. Cytoplasmic microtubule-based motor proteins. Curr Opin Cell Biol. 1993 Feb;5(1):95–104. doi: 10.1016/s0955-0674(05)80014-6. [DOI] [PubMed] [Google Scholar]
- Steuer E. R., Wordeman L., Schroer T. A., Sheetz M. P. Localization of cytoplasmic dynein to mitotic spindles and kinetochores. Nature. 1990 May 17;345(6272):266–268. doi: 10.1038/345266a0. [DOI] [PubMed] [Google Scholar]
- Theurkauf W. E., Hawley R. S. Meiotic spindle assembly in Drosophila females: behavior of nonexchange chromosomes and the effects of mutations in the nod kinesin-like protein. J Cell Biol. 1992 Mar;116(5):1167–1180. doi: 10.1083/jcb.116.5.1167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Threlkeld A., Adler R., Hewitt A. T. Proteoglycan biosynthesis by chick embryo retina glial-like cells. Dev Biol. 1989 Apr;132(2):559–568. doi: 10.1016/0012-1606(89)90251-0. [DOI] [PubMed] [Google Scholar]
- Turner R., Tjian R. Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. Science. 1989 Mar 31;243(4899):1689–1694. doi: 10.1126/science.2494701. [DOI] [PubMed] [Google Scholar]
- Vale R. D., Goldstein L. S. One motor, many tails: an expanding repertoire of force-generating enzymes. Cell. 1990 Mar 23;60(6):883–885. doi: 10.1016/0092-8674(90)90334-b. [DOI] [PubMed] [Google Scholar]
- Vale R. D., Reese T. S., Sheetz M. P. Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell. 1985 Aug;42(1):39–50. doi: 10.1016/s0092-8674(85)80099-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vernos I., Heasman J., Wylie C. Multiple kinesin-like transcripts in Xenopus oocytes. Dev Biol. 1993 May;157(1):232–239. doi: 10.1006/dbio.1993.1127. [DOI] [PubMed] [Google Scholar]
- Walker R. A., Sheetz M. P. Cytoplasmic microtubule-associated motors. Annu Rev Biochem. 1993;62:429–451. doi: 10.1146/annurev.bi.62.070193.002241. [DOI] [PubMed] [Google Scholar]
- Wang S. Z., Adler R. A developmentally regulated basic-leucine zipper-like gene and its expression in embryonic retina and lens. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1351–1355. doi: 10.1073/pnas.91.4.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang J. T., Laymon R. A., Goldstein L. S. A three-domain structure of kinesin heavy chain revealed by DNA sequence and microtubule binding analyses. Cell. 1989 Mar 10;56(5):879–889. doi: 10.1016/0092-8674(89)90692-2. [DOI] [PubMed] [Google Scholar]