Regulation of Cellular Growth by HspBP1

DESCRIPTION (provided by applicant): All eukaryotic cells studied to date contain a set of proteins known as heat stress proteins (Hsps) that provide protection from various environmental stresses. Hsp70 is a heat stress protein that is elevated in numerous types of cancer cells. Lowering Hsp70 expression in cancer cells results in cell death. This laboratory has isolated a novel human cDNA that codes for a Hsp70 binding and inhibiting protein called HspBPI. Data from this laboratory has shown that HspBPI levels are also elevated in a variety of different cancer types. One hypothesis is that HspBPI is also needed for transformation and is responsible for the alteration of growth control. A second hypothesis is that the elevated HspBPI levels are a response to the elevated Hsp70 levels. An explanation could be that the primary event is an increase in Hsp70 levels, which supports transformation. The cell's response to such an increase would be to try and block the activity of Hsp70 by expressing higher levels of HspBPI, an inhibitor. However, not enough HspBPI is synthesized to block the increase in Hsp70 resulting in a transformed phenotype. To test these hypotheses, we will either increase or decrease the levels of HspBPI in several cell lines and determine if there alterations in a number of parameters used to measure cell proliferation, cell death and tumor formation. Understanding the role of HspBPI in cancer cells will provide information that can be used to develop new therapies by defining a new target for drug discovery.