Regulation of Cellular Growth by HspBP1

描述(申请人提供)：到目前为止，所有被研究的真核细胞都含有一组被称为热应激蛋白(HSPs)的蛋白质，它们提供了对各种环境压力的保护。HSP70是一种热应激蛋白，在多种类型的癌细胞中都会升高。降低癌细胞中Hsp70的表达会导致细胞死亡。这个实验室已经分离出一种新的人类基因，它编码Hsp70结合和抑制蛋白，称为HspBPI。该实验室的数据显示，HspBPI水平在各种不同类型的癌症中也会升高。一种假设是，HspBPI也是转化所必需的，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。一个解释可能是，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来阻断Hsp70的活性，HspBPI是一种抑制因子。然而，合成的HspBPI不足以阻止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发生变化。了解HspBPI在癌细胞中的作用将提供信息，通过定义新的药物发现目标来开发新的治疗方法。

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.