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称为热应激蛋白（Hsps）的蛋白质，可提供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Hsp70在癌细胞中的表达可导致细胞死亡。该实验室已经分离出一种新的人类cDNA，该cDNA编码Hsp70结合和抑制蛋白HspBPI。该实验室的数据表明，HspBPI水平在各种不同类型的癌症中也会升高。一种假设是，HspBPI也需要转化，并负责改变生长控制。第二种假设是HspBPI水平升高是对Hsp70水平升高的反应。一种解释可能是主要事件是支持转化的Hsp70水平的增加。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）来阻止Hsp70的活性。然而，没有足够的HspBPI合成来阻止Hsp70的增加，从而导致表型转化。为了验证这些假设，我们将增加或降低几种细胞系中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一些参数是否有变化。了解HspBPI在癌细胞中的作用将提供信息，可用于通过定义药物发现的新靶点来开发新疗法。

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.