Regulation of Cellular Growth by HspBP1

描述（由申请人提供）：迄今为止研究的所有真核细胞都含有一组被称为热应激蛋白（Hsps）的蛋白质，其提供对各种环境应激的保护。Hsp70是一种热应激蛋白，在许多类型的癌细胞中升高。降低癌细胞中的Hsp70表达导致细胞死亡。该实验室已经分离出一种新的编码Hsp70结合和抑制蛋白HspBPI的人类cDNA。来自该实验室的数据表明，HspBPI水平在各种不同的癌症类型中也会升高。一种假设是HspBPI也是转化所需的，并且负责生长控制的改变。第二个假设是升高的HspBPI水平是对升高的Hsp70水平的响应。一种解释可能是，主要事件是Hsp70水平的增加，这支持了转化。细胞对这种增加的反应是试图通过表达更高水平的HspBPI（一种抑制剂）来阻断Hsp70的活性。然而，合成的HspBPI不足以阻断Hsp70的增加，从而导致转化的表型。为了检验这些假设，我们将在几种细胞系中增加或降低HspBPI的水平，并确定用于测量细胞增殖、细胞死亡和肿瘤形成的许多参数是否发生变化。了解HspBPI在癌细胞中的作用将提供可用于通过定义药物发现的新靶点来开发新疗法的信息。

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.