Tang K. Tang

    Ph.D. Human Genetics, Yale University

Research

A. Cell Cycle Control and Cancer Genetic Instability

    Genetic instability is a common characteristic of many human cancers. Although, little is known about the mechanism that generates this genetic abnormality, the missegregation of chromosomes through the assembly of dysfunctional mitotic spindles may play essential roles. The centrosome functions as the major microtubule organizing center of the cells. During cell mitosis, the centrosome organizes the microtubule array of the mitotic spindle and thereby makes possible equal segregation of sister chromatids into two daughter cells. Indeed, many reports have shown that defects in centrosome function lead to aneuploidy and genetic instability in cancer cells. We previously identified several centrosomal proteins including aurora-A, CPAP, protein 4.1 and NuMA. In this project, we propose to systematically and qualitatively analyze the protein composition of centrosome by proteomics approach (MALDI/TOF), particularly focusing on the identification of novel centrosomal kinases and their substrates. Furthermore, we will examine the possible roles of these newly identified proteins involved in cell mitosis and genomic instability.

B. Gene Regulation and Germ Cell Development

    Spermatogenesis in mammals is a complex system that leads to the formation of male gametes. During spermatogenesis, male germ cells undergo major morphological and biochemical changes, which are regulated by the stage-specific transcriptional and translational activation of numerous genes and protein kinases. We previously identified a novel serine/threonine kinase, Aie1 (aurora-C) and its gene regulator Tzfp (a novel testis zinc finger protein). Both Aie1 and Tzfp are expressed in testis and particularly in meiotic pachytene spermatocytes, suggesting a possible role of these two proteins involved in spermatogenesis. Recently, we demonstrate that Tzfp binds to the promoter region of Aie1 gene through its carboxyl zinc finger domain, which suggests that the expression of Aie1 gene may be regulated by tzfp. We currently produced a series of Tzfp gene knockout mice. The possible roles of Aie1 and Tzfp involved in spermatogenesis are currently under investigation. The results from these studies should explore the unrevealed signaling pathways and regulation in germ cell development in the future.

Publications

  1. Huang,C.S., Sung,Y.C., Huang,M.J., Yang,C.S., Shei,W.S., and Tang,T.K.* (1998) Content of reduced glutathione and consequences in recipients of G6PD deficient red blood cells. Am. J. Hematol. 57, 187-192.
  2. Kuo,W.Y and Tang,T.K.* (1998) Effects of G6PD overexpression in NIH3T3 cells treated with tert-butyl hydroperoxide or paraquat. Free Rad. Biol. Med. 24, 1130-1138.
  3. Tang, C.J.C. and Tang,T.K.* (1998) The 30 kDa domain of protein 4.1 mediates its binding to the carboxyl terminus of pICln, a protein involved in volume regulation. Blood 92, 1442-1447.
  4. Tseng,T.C., Chen,S.H, Hsu,Y.P P., and Tang,T.K.* (1998) A protein kinase profile of sperms and eggs: Cloning and characterization of two novel protein kinases (AIE1 and AIE2), related to yeast and fly chromosome segregator regulators. DNA Cell Biol. 17, 823-833.
  5. Cheng,Y.S., Tang,T.K., and Hwang,M.J. (1999) Amino acid conservation and clinical severity of human glucose-6-phosphate dehydrogenase mutations. J. Biomed. Sci. 6, 106-114.
  6. Lin,W.C.*, Lai,C.H., Tang,C.J. C., Huang,C.J., and Tang,T.K.* (1999) Identification and gene structure of a novel human PLZF related transcription factor gene, TZFP. Biochem. Biophy. Res. Commun. 264, 789-795.
  7. Kuo,W.Y., Lin,J.Y., and Tang,T.K.* (2000) Human glucose-6-phosphate dehydrogenase (G6PD) gene transforms NIH 3T3 cells and induces tumors in nude mice. Int. J. Cancer 85, 857-864.
  8. Hou,C.L., Tang,C.J. C., Roffler,S.R., and Tang,T.K.* (2000) Protein 4.1R binds to eIF3-p44 suggests an interaction between the cytoskeletal network and the translation apparatus. Blood 96, 747-753.
  9. Hu,H.M., Tseng,T.C., Chuang,C.K., Lee,M.J., and Tang,T.K.* (2000) Genomic organization, expression, and chromosome localization of a third aurora-related kinase gene, Aie1. DNA Cell Biol. 19, 679-688.
    Hung,L.Y., Tang,C.J.C., Tang,T.K.* (2000). P4.1R (135 kDa) interacts with a novel centrosomal protein (CPAP), which is associated with the -tubulin complex. Mol. Cell. Biol. 20, 7813-7825.
  10. Tang,C.J.C., Chuang,C.K., Hu,H.M., and Tang,T.K.* (2001) The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. J. Biol. Chem. 276, 19631-19639.
  11. Chen,S.H., and TangT.K.* (2002) Mutational analysis of the phosphorylation sites of the Aie1(aurora-C) kinase in vitro. DNA Cell Biol. 21, 41-46.
  12. Peng,B., Sutherland,K.D., Sum,E.Y.M., Olayioye,M., Wittlin,S., Tang,T.K., Lindeman,G.J., and Visvader,J.E. (2002) CPAP is novel Stat5-interacting cofactor that augments Stat5-mediated transcriptional activity. Mol. Endocrinol. 16, 2019-2033.
  13. Tang, C-J. C., Hu, H-M, and Tang, T. K.* (2004) NuMA (Nuclear Mitotic Apparatus Protein) expression and function in mouse oocyte and early embryo. J. Biomed. Sci. 11, 370-376.
  14. Hung, L-Y., Chen, H-L., Chang, C-W., Li, B-R., and Tang, T. K.* (2004) Identification of a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly. Mol. Biol. Cell. 15, 2697-2706.

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