John L. Wang
Research Interests
The work described
below is carried out in close collaboration with the laboratory of Dr. Ron
Patterson (Department of Microbiology and Molecular Genetics).
The research
interests of our laboratories are focused on two carbohydrate-binding proteins,
galectin-1 and galectin-3. The galectins comprise a family of galactose-binding
proteins that share characteristic amino acid sequences in the carbohydrate
recognition domain of the polypeptides. Our interest in this system stemmed
from the observation that galectin-3 was found as a ribonucleoprotein complex
in the nucleus. Using nuclear extracts derived from HeLa cells, capable
of carrying out splicing of pre-mRNA in a cell-free assay, depletion and
reconstitution experiments demonstrated that galectins-1 and -3 are splicing
factors. More recently, we have documented that galectins-1 and -3 both
independently bind to a protein designated Gemin4. The significance of this
finding lies in the fact that other investigators had shown that Gemin4
is one component of a macromolecular complex, the SMN complex, that plays
important roles in the biogenesis, delivery, and regeneration of small nuclear
ribonucleoprotein particles (snRNPs) for spliceosome assembly. On the basis
of these and other observations, the immediate objectives of our research
include:
(a) to delineate and characterize the components and interactions of the ribonucleoprotein complex on which galectins-1 and -3 have been found;
(b) to define the step(s) during which galectins-1 and -3 participate in splicing;
(c) to test, by site-directed mutagenesis, whether carbohydrate-binding is required for the role of; galectins in the splicing reaction;and
(d) to study the nucleo-cytoplasmic shuttling properties of galectin-3, in terms of import and export signals and in terms of a possible role in mRNA transport.
Recent Publications
Wang, J.L., Haudek, K.C., Voss, P.G. and Patterson, R.J. (2008) Nuclear and cytoplasmic localization of galectin-1 and galectin-3 and their roles in pre-mRNA splicing, in Galectins (A.A. Klyosov, Z.J. Witczak, and D. Platt, eds.), John Wiley & Sons, pp. 87-95. Link to pdf
Voss, P.G., Gray, R.M., Dickey, S.W., Wang, W., Park, J.W., Kasai, K., Hirabayashi, J., Patterson, R.J., and Wang, J.L. (2008) Dissociation of the carbohydrate-binding and splicing activities of galectin-1, Arch. Biochem. Biophys., 478: 18-25. Link to pdf
Gray, R.M., Davis, M.J., Ruby, K.M., Voss, P.G., Patterson, R.J., and Wang, J.L. (2008) Distinct effects on splicing of two monoclonal antibodies directed against the amino-terminal domain of galectin-3, Arch. Biochem. Biophys. 475: 100-108. Link to pdf
Arnoys, E.A. and Wang, J.L. (2007) Dual localization: proteins in extracellular and intracellular compartments. Acta Histochemica 109: 89-110. Link to pdf