Tang K. Tang
Ph.D. Human Genetics, Yale University
A. Cell Cycle Control and Cancer
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
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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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,
- 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.
- 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.
- 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,
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 ƒ×-tubulin
complex. Mol. Cell. Biol. 20, 7813-7825.
- 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.
- 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.
- 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.
- 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.
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,