Regulation of Cellular Growth by HspBP1

HspBP1 对细胞生长的调节

• 批准号: 7090355
• 负责人: Vince Guerriero
• 金额: $ 17.59万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7090355
• 关键词: SCID mouse; antineoplastics; binding proteins; bioassay; cell death; cell growth regulation; cell line; cell proliferation; germ free condition; heat shock proteins; inhibitor /antagonist; molecular chaperones; neoplasm /cancer pharmacology; neoplastic cell; neoplastic transformation; phenotype; protein denaturation; protein folding; protein structure function

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.

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，可提供针对各种环境应激的保护。 Hsp70 是一种热应激蛋白，在多种类型的癌细胞中都会升高。降低癌细胞中的 Hsp70 表达会导致细胞死亡。该实验室分离出了一种新型人类 cDNA，它编码 Hsp70 结合和抑制蛋白，称为 HspBPI。该实验室的数据表明，多种不同癌症类型中的 HspBPI 水平也会升高。一种假设是 HspBPI 也是转化所必需的，并且负责改变生长控制。第二个假设是 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 Hsp70 水平的增加，这支持转化。细胞对这种增加的反应是尝试通过表达更高水平的 HspBPI（一种抑制剂）来阻断 Hsp70 的活性。然而，没有合成足够的 HspBPI 来阻止 Hsp70 的增加，从而导致表型转化。为了检验这些假设，我们将增加或减少几种细胞系中的 HspBPI 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为通过定义药物发现的新靶标来提供可用于开发新疗法的信息。