The University of Arizona

Regulation of The Heat Stress Protein Hsp70 by HspBP1

-Vince Guerriero, Associate Professor, Dept. of Animal Sciences, University of Arizona

All cells contain a set of proteins known as heat stress proteins that provide protection from various environmental stresses such as elevated temperatures, exposure to heavy metals, and hypoxia. The research focus in this laboratory has been on the characterization of proteins that regulate heat stress proteins and how to use these proteins as regulators of the heat stress response. Our efforts have resulted in the discovery of a novel protein called HspBP1. HspBP1 binds to and inhibits the activity of the heat stress protein Hsp70.

The importance of Hsp70 as a cellular regulator has dramatically increased over the years due to its association with a number of cellular processes including protein refolding, apoptosis, cell proliferation and protein degradation. Misfolded proteins are a characteristic of some neuromuscular diseases and therefore studies funded by the Muscular Dystrophy Association are focused on understanding the regulation of Hsp70 activity on protein refolding. In addition, elevated Hsp70 levels have been reported in a number of different types of cancer and lowering these levels causes cancer cells to undergo apoptosis. Research currently funded by the National Institutes of Health is focused on understanding the role of HspBP1 in cancer and cell growth.

This research has resulted in numerous collaborations with laboratories both in the United States and other countries including Germany, Russia, Hungary, Japan, and Brazil. Examples of these collaborations include a crystallography group that produced a model of HspBP1 binding to the ATPase domain of Hsp70. This model has provided new insights on the mechanism of HspBP1 regulation of Hsp70 activity and information that will be used to design mutants for testing of the model. In addition, we have found that HspBP1 is presence in human sera and the levels of antibodies against HspBP1 are elevated in HIV infected patients. These new findings have provided support for the hypothesis that HspBP1 can function both inside and outside the cell.

Understanding how other proteins can regulate Hsp70 will provide information on the regulation of a diverse number of cellular activities and will have importance in both basic as well as applied research. The identification of a novel protein (HspBP1) that can alter the activity of a major intracellular regulator (Hsp70) has provided numerous opportunities for understanding and modifying different cell functions.

Recent Articles

to top