Rekha C. Patel

Associate Professor of Biological Sciences
Ph. D. 1987, Indian Institute of Science
803-777-1853
patelr@biol.sc.edu

Regulation of cell proliferation and apoptosis.

Cellular mechanisms that regulate cell proliferation and programmed cell death (apoptosis) have fascinated biologists over many decades. Study of regulatory pathways for cell cycle and apoptosis is directly relevant to cancer and other important medical problems. Research in my lab focuses on the interferon (IFN) induced, double-stranded RNA activated protein kinase, PKR. PKR is a key mediator of the antiviral and antiproliferative effects of interferon. Although the majority of earlier research on PKR had focused on its participation in the IFN's inhibitory action on viral infection, substantial evidence gathered in recent years shows PKR's involvement in growth regulation, differentiation, apoptosis and signal transduction. The goal of research in my lab is to understand the regulation of PKR activity in cells and to elucidate the pathways by which it modulates cell proliferation and programmed cell death. We have primarily focused on two activators of PKR: heparin, a polyanionic agent and PACT, a cellular protein activator of PKR. Our recent results have indicated that heparin-activated PKR regulates vascular smooth muscle proliferation by preventing down-regulation of p27kip1 protein levels in response to mitogens. Since proliferation of vascular smooth muscle cells is a key factor in development of atherosclerotic lesions, understanding the pathways of cell cycle regulation in these cells is of interest. We are also interested in elucidating how PACT regulates PKR activity to induce apoptosis in response to stress signals.

Selected Publications:

Trivedi, C. M., Patel, R. C., and Patel C. V. (2007) Homeobox Gene HOXA9 Inhibits Nuclear Factor - kappa B Dependent Activation of Endothelium. Atherosclerosis, In Press.

Fasciano, S., Kaufman, A., and Patel, R. C. (2007) Expression of PACT is regulated by Sp1 transcription factor. Gene, 388(1-2), 74-82.

Fasciano, S., Patel, R. C., Handy, I., and Patel, C. V. (2005) Regulation of vascular smooth muscle proliferation by heparin: Inhibition of cyclin-dependent kinase 2 activity by p27kip1. J. Biol. Chem. 280(16), 15682-15689.

Fasciano, S., Hutchins, B., Handy, I., and Patel, R. C. (2005) Identification of the heparin-binding domains of the interferon-induced protein kinase, PKR. FEBS Journal 272(6), 1425-1439.

Gupta, V., Huang, X., and Patel, R. C. (2003) The carboxy-terminal, M3 motifs of PACT and TRBP have opposite effects on PKR activity. Virology 315, 283-291.

Gupta, V., and Patel, R. C. (2002) Proapoptotic protein PACT is expressed at high levels in colonic epithelial cells in mice. Am. J. Gastrointest. Liver Physiol. 283, G801-G808.

Huang, X., Hutchins, B., and Patel, R. C. (2002) The carboxy-terminal, third conserved motif of the protein activator PACT plays an essential role in the activation of double-stranded-RNA-dependent protein kinase (PKR). Biochem. J. 366, 175-186.

Patel, R. C. , Handy, I., Patel, C. V. (2002) Contribution of double-stranded RNA-activated protein kinase toward antiproliferative actions of heparin on vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 221, 439-1444.

Patel, C. V., Handy, I., Goldsmith, T., and Patel, R. C. (2000) PACT, a stress-modulated cellular activator of interferon-induced double-stranded RNA-activated protein kinase, PKR. J. Biol. Chem. 275, 37993-37998.

Patel, R. C. , Vestal, D. J., Xu, Z., Bandyopadhyay, S., Guo, W., Erme, S. M., Wiliams, B. R. G. and Sen, G. C. (1999) DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR. J. Biol. Chem. 274, 20432-20437.

Patel, R. C. and Sen, G. C. (1998) Requirement of PKR dimerization mediated by specific hydrophobic residues for its activation by double-strandedRNA and its antigrowth effects in yeast. Mol Cell. Biol. 18, 7009-7019.

Patel, R. C. and Sen, G. C. (1998) PACT, a protein activator of the interferon-induced protein kinase, PKR. EMBO J. 17, 4379-4390.

Patel, R. C. , Stanton, P. and Sen, G. C. (1996) Specific mutations near the amino terminus of double-stranded RNA-dependent protein kinase (PKR) differentially affect its double-stranded RNA binding and dimerization properties. J. Biol. Chem. 271, 25657-25663.

Patel, R. C. , Stanton, P., McMillan, N. M. J., Williams, B.R.G., and Sen, G.C.(1995) The interferon-inducible double-stranded RNA-activated protein kinase, PKR, self-associates in vitro and in vivo. Proc. Natl. Acad. Sci. USA. 92, 8283-8287.

Patel, R. C. and Sen, G. C. (1994) Characterization of the interactions between double-stranded RNA and the double-stranded RNA binding domain of the interferon induced protein kinase. Cell. Mol. Biol. Res. 40, 671-682.

Patel, R. C. , Stanton, P. and Sen, G. C. (1994) Role of the amino terminal residues of the interferon induced protein kinase in its activation by double-stranded RNA and Heparin. J. Biol. Chem. 269, 18593-18598.

Patel, R. C. and Sen, G. C. (1992) Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase. J. Biol. Chem. 267(11), 7671-7676.

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