THE ROLE OF GENE DnudC IN A TUMOR SUPPRESSOR GENE IN OOGENESIS
Abstract
Intracellular nuclear migration participates in the establishment of cell polarity, in asymmetrical cell division, in karyogamy and a myriad of other cellular important functions. It appears to play a role in tumor cell migration, metastasis and human brain development. In this study, the DnudC gene a Drosophila homolog to Aspergillus nudC gene and its implication in tumor suppression function was characterized. The results of this study indicated that DnudC is expressed during development of embryos as well as during larval stages and adults. The mutation of this gene indicated that the product(s) of DnudC gene is an essential for survival during early larval stages, where, homozygous larvae die in 2nd instar larvae with many melanotic tumors as well as is essential for oogenesis. Further more, loss of heterozygousity for this mutation induce overproliferation in larval and adults as indicated by somatic clone assay using FLP/FRT system. The product of DnudC gene is maternally supplied in egg and this product(s) is needed in early developmental stages during development of embryos.References
Aumais, J. P., J. R. Tunstead, R. S. McNeil, B. T. Schaar, S. K. McConnell, S. H. Lin, G. D. Clark and L. Y. Yu-Lee (2001). NudC associates with Lis1 and the dynein motor at the leading pole of neurons. J. Neurosci 21, RC187.
Aumais, J. P., S. N. Williams, W. Luo, M. Nishino, K. A. Caldwell, G. A. Caldwell, S. H. Lin and L. Y. Yu- Lee (2003). Role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis. J. Cell Sci., 116: 1991-2003.
Bellotto, M., D. Bopp, K. A. Senti, R. Burke, P. Deak, P. Maroy, B. Dickson, K. Basler and E. Hafen (2002). Maternal-effect loci involved in Drosophila oogenesis and embryogenesis: P elementinduced mutations on the third chromosome. Int. J. Dev. Biol., 46: 149-157.
Chou, T. B. and N. Perrimon (1996). The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics, 144: 1673-1679.
Cummings, C. A. and C. Cronmiller (1994). The daughterless gene functions together with Notch and Delta in the control of ovarian follicle development in Drosophila. Development, 120: 381-394.
Cunniff, J., Y. H. Chiu, N. R. Morris and R. Warrior (1997). Characterization of DnudC, the Drosophila homolog of an Aspergillus gene that functions in nuclear motility. Mech. Dev., 66: 55-68.
FLYBASE, (1999). The FlyBase database of the Drosophila Genome Projects and community literature. Nucleic Acids Res. 27:85-88. http://flybase.bio.indiana.edu/.
Gao, X., T. P. Neufeld and D. Pan (2000). Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev. Biol., 221: 404- 418.
Gocke, C. D., S. A. Osmani and B. A. Miller (2000). The human homologue of the Aspergillus nuclear migration gene nudC is preferentially expressed in dividing cells and ciliated epithelia. Histochem. Cell Biol., 114: 293-301.
Golsteyn, R. M., K. E. Mundt, A. M. Fry and E. A. Nigg (1995). Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function. J. Cell Biol., 129: 1617-1628.
Häcker, U., S. Nystedt, M. P. Barmchi, C. Horn and E. A. Wimmer (2003). piggyBac-based insertional mutagenesis in the presence of stably integrated P elements in Drosophila. Proc. Natl. Acad. Sci., USA, 100: 7720-7725.
Helmstaedt, K., K. Laubinger, K. Voßkuhl, O. Bayram, S. Busch, M. Hoppert, O. Valerius, S. Seiler and G. H. Braus (2008). The nuclear migration protein NUDF/LIS1 forms a complex with NUDC and BNFA at spindle pole bodies. Eukaryot Cell. 2008 Apr 4. [Epub ahead of print].
Horn, C., B. Jaunich and E. A. Wimmer (2000). Highly sensitive, fluorescent transformation marker for Drosophila transgenesis. Dev. Genes Evol., 210: 623-629.
Horn, C., N. Offen, S. Nystedt, U. Häcker and E. A. Wimmer (2003). piggy- Bac-Based Insertional Mutagenesis and Enhancer Detection as a Tool for Functional Insect Genomics. Genetics, 163: 647-661.
Huang, M. A., E. J. Rehm and G. M. Rubin (2000). Recovery of DNA sequences flanking P-element insertions: inverse PCR and plasmid rescue, pp. 429-437 in Drosophila Protocols, (W. SULLIVAN, M. ASHBURNER and R. S. HAWLEY. Eds) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Ito, N. and G. M. Rubin (1999). gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell, 96: 529-539. Karki, S. and E. L. Holzbaur (1999). Cytoplasmic dynein and dynactin in cell division and intracellular transport. Curr. Opin. Cell Biol., 11: 45-53.
Lee, K. S., T. Z. Grenfell, F. R. Yarm and R. L. Erikson (1998). Mutation of the Polo-box disrupts localization and mitotic functions of the mammalian Polo kinase Plk. Proc. Natl. Acad. Sci., USA, 95: 9301- 9306.
Lindsley, D. L. and G. G. Zimm (1992). The genome of Drosophila melanogaster. San Diego: Academic Press.
Liu, X. and R. L. Erikson (2002). Activation of Cdc2/cyclin B and inhibition of centrosome amplification in cells depleted of Plk1 by siRNA. Proc. Natl. Acad. Sci., USA, 99: 8672-8676.
Matsumoto, N. and D. H. Ledbette, (1999). Molecular cloning and characterization of the human NUDC gene. Hum. Genet., 104: 498-504.
Miller, B. A., M. Y. Zhang, C. D. Gocke, C. De Souza, A. H. Osmani, C. Lynch, D. J. avies, L. Bell and S. A. Osmani (1999). A homolog of the fungal nuclear migration gene nudC is involved in normal and malignant human hematopoiesis. Exp. Hematol., 27: 742-750.
Minakhina, S. and R. Steward (2006). Melanotic Mutants in Drosophila: Pathways and Phenotypes. Genetics, 174: 253-263.
Moberg, K. H., S. Schelble, S. K. Burdick and I. K. Hariharan (2005). Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth. Dev. Cell, 9: 699- 710.
Morris, N. R. (2000). Nuclear migration. From fungi to the mammalian brain. J. Cell Biol., 148: 1097- 1101.
Morris, S. M. and L. Y. Yu-Lee (1998). Expression of RNUDC, a potential nuclear movement protein, in mammalian cells: localization to the Golgi apparatus. Exp. Cell Res., 238: 23-32.
Mountain, V. and D. A. Compton (2000). Dissecting the role of molecular motors in the mitotic spindle. Anat. Rec., 261: 14-24.
Nigg, E. A. (1998). Polo-like kinases: positive regulators of cell division from start to finish. Curr. Opin. Cell Biol., 10: 776-83.
Nishino, M., Y. Kurasawa, R. Evans, S. H. Lin, B. R. Brinkley and L. Y. Yu-Lee (2006). NudC is required for Plk1 targeting to the kinetochore and chromosome congression. Curr. Biol., 2006 Jul 25; 16: 1414-1421.
Nishino, M., Y. Kurasawa, R. Evans, S. H. Lin, B. R. Brinkley and L. Y. Yu-Lee (2006). NudC is required for Plk1 targeting to the kinetochore and chromosome congression. Curr. Biol., 16: 1414- 1421.
Osmani, A. H., S. A. Osmani and N. R. Morris (1990). The molecular cloning and identification of a gene product specifically required for nuclear movement in Aspergillus nidulans. J. Cell Biol., 111: 543-51.
Song, S., T. Z. Grenfell, S. Garfield, R. L. Erikson and K. S. Lee (2000). Essential function of the Polo box of Cdc5 in subcellular localization and induction of cytokinetic structures. Mol. Cell Biol., 20: 286-298.
Sumara, I., E. Vorlaufer, P. T. Stukenberg, O. Kelm, N. Redemann, E. A. Nigg and J. M. Peters (2002). The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase. Mol. Cell, 9: 515-525.
Sunkel, C. E. and D. M. Glover (1988). Polo a mitotic mutant of Drosophila displaying abnormal spindle poles. J. Cell Sci., 89: 25-38.
Tapon, N., K. F. Harvey, D. W. Bell, D. C. Wahrer, T. A. Schiripo, D. A. Haber and I. K. Hariharan (2002). salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell, 110: 467-478.
Tapon, N., N. Ito, B. J. Dickson, J. E. Treisman and I. K. Hariharan (2001). The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell, 105: 345-355.
Tautz, D. and P. Christine (1989). A nonradioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma, 98: 81- 85.
Vale, R. D. (2003). The molecular motor toolbox for intracellular transport. Cell, 112: 467-480.
van Vugt, M. A. and R. H. Medema (2005). Getting in and out of mitosis with Polo-like kinase-1. Oncogene, 24: 2844-2859.
Watson, K. L., R. W. Justice and P. J. Bryant (1994). Drosophila in cancer research: the first fifty tumor suppressor genes. J. Cell Sci., 18 (Suppl.): 19-33.
Wynshaw-Boris, A. and M. J. Gambello (2001). LIS1 and dynein motor function in neuronal migration and development. Genes Dev., 15: 639-651.
Xiang, X., A. H. Osmani, S. A. Osmani, M. Xin and N. R. Morris (1995). NudF, a nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene required for neuronal migration. Mol. Biol. Cell, 6: 297-310.
Xu, T. and S. D. Harrison (1994). In: Methods in Cell Biology (Goldstein, L.S.B. and Fyrberg, E.A., Eds.), Vol. 44, pp. 655-681,
Academic Press, New York. Xu, T., W. Wang, S. Zhang, R. A. Stewart and W. Yu (1995). Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development, 121: 1053-1063.
Zhang, J., S. Li, R. Fischer and X. Xiang (2003). Accumulation of cytoplasmic dynein and dynactin at microtubule plus ends in Aspergillus nidulans is kinesin dependent. Mol. Biol. Cell, 14: 1479-1488.
Zhang, M. Y., N. N. Huang, G. A. Clawson, S. A. Osmani, W. Pan, P. Xin, M. S. Razzaque and B. A. Miller (2002). Involvement of the fungal nuclear migration gene nudC human homolog in cell proliferation and mitotic spindle formation. Exp. Cell Res., 273: 73- 84.
Zhou, T., J. P. Aumais, X. Liu, L. Y. Yu- Lee and R. L. Erikson (2003). A role for Plk1 phosphorylation of NudC in cytokinesis. Dev. Cell, 5: 127-138.
Zhou, T., W. Zimmerman, X. Liu and R. L. Erikson (2006). A mammalian NudC-like protein essential for dynein stability and cell viability. Proc. Natl. Acad. Sci., USA, 103: 9039-9044.
