It is well established that all cells respond to stresses by the synthesis of a set of proteins called heat stress proteins (Hsps). The main focus of research in my laboratory is the study of Hsps and the function of these proteins in the cell. Conditions that induce this new synthesis include elevated temperatures, hypoxia, amino acid analogs, ethanol, arsenite, heavy metals, UV irradiations, and inhibitors of mitochondrial functions. Hsps are thought to help the cell recover from stress and provide a temporary protection from further stress. The most studied of these proteins has a molecular weight of approximately 70 kDa and is, therefore, called the Hsp70. Currently, it is thought that Hsp70 helps the cell survive stress by two different mechanisms. First, Hsp70 binds to partially denatured proteins and assists in refolding these proteins into more stable native structures. Second, recent studies have shown that increased levels of Hsp70 in a cell can inhibit apoptosis and cell death.
Recently, my laboratory has isolated a Hsp70 interacting protein cDNA (HspBP1) from a human heart cDNA library using the yeast two-hybrid system. The derived amino sequence of HspBP1 is unique and, therefore, represents a new regulator of Hsp70. HspBP1 inhibits the Hsp40 activated Hsp70 ATPase activity. The Hsp40 activated ATPase activity is essential for the renaturation activity of Hsp70. Therefore, as expected, HspBP1 inhibits Hsp70 mediated luciferase renaturation. Current research is focused on the role of HspBP1 in the regulation of apoptosis. The approach for these studies is to over expression HspBP1 in culture cells to determine the effect on apoptosis. Studies are also in progress to better understand the interaction between Hsp70 and HspBP1 by defining the region on HspBP1 that interacts with the ATPase domain of Hsp70.
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Raynes, D.A., C.A. Thomson, J. Stroster, T. Newton, P. Cuneo, and V. Guerriero. 2006. Human serum contains detectable levels of the Hsp70 cochaperone HspBP1 and antibodies bound to HspBP1. Journal of Immunoassay and Immunochemistry 27: 251-264.
Bernstein, H., C.M. Payne, K. Kunke, C.L. Crowley-Weber, C.N. Waltmire, K. Dvorakova, H. Holubec, C. Bernstein, R.R. Vaillancourt, D.A. Raynes, V. Guerriero, and H. Garewal. 2004. A proteomic study of deoxycholate-induced apoptosis. Carcinogenesis 25: 681-692.
Raynes, D.A., M.A. Graner, R. Bagatell, C. McLellan, and V. Guerriero. 2003. Increased expression of the Hsp70 cochaperone HspBP1 in tumors. Tumor Biology 24: 281-285.
McLellan, C.A., D.A. Raynes, and V. Guerriero. 2003. HspBP1, an Hsp70 cochaperone, has two structural domains and is capable of altering the conformation of the Hsp70 ATPase domain. Journal of Biological Chemistry 278: 19017-19022.
Kabani, M., C. McLellan, D.A. Raynes, V. Guerriero, and J.L. Brodsky. 2002. HspBP1, a homologue of the yeast Fes1 and Sls1 proteins, is an Hsc70 nucleotide exchange factor. FEBS Letters 531: 339-342.
Raynes, D.A., and V. Guerriero. 2000. Isolation and characterization of isoforms HspBP1, an inhibitor of Hsp70. Biochimica et Biophysica Acta 1490: 203-207.
