Regulation of Cellular Growth by HspBP1

HspBP1 对细胞生长的调节

• 批准号: 7230175
• 负责人: Vince Guerriero
• 金额: $ 17.09万
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230175
• 关键词: Anchorage-Independent Growth; Antineoplastic Agents; Binding; Biological Assay; Cell Death; Cell Line; Cell Proliferation; Cells; Code; Complementary DNA; Data; Eukaryotic Cell; Event; Exhibits; Growth; Heat Stress Disorders; Heat shock proteins; Human; Invasive; Laboratories; Malignant Neoplasms; Measures; Molecular Chaperones; Normal Cell; Numbers; Personal Satisfaction; Phenotype; Proteins; Regulation; Research Personnel; Role; SCID Mice; Set protein; Stress; Testing; cancer cell; cancer type; cell growth; drug discovery; inhibitor/antagonist; novel; programs; response; stress protein; tumor

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包含一组称为热应激蛋白（HSP）的蛋白质，可保护免受各种环境应力的保护。 HSP70是一种热应激蛋白，在多种类型的癌细胞中升高。降低癌细胞中HSP70的表达会导致细胞死亡。该实验室已经分离了一种新型的人cDNA，该c cDNA编码HSP70结合并抑制称为HSPBPI的蛋白质。该实验室的数据表明，在各种不同的癌症类型中，HSPBPI水平也升高。一种假设是转化也需要HSPBPI，并负责改变生长控制。第二个假设是HSPBPI水平升高是对HSP70升高水平的响应。一个解释可能是主要事件是HSP70级别的增加，这支持转换。细胞对这种增加的反应是尝试通过表达较高水平的HspBPI（抑制剂）来阻止HSP70的活性。但是，没有足够的HspBPI合成以阻止HSP70的增加，从而导致转化的表型。为了检验这些假设，我们将增加或降低几个细胞系中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许多参数的改变。了解HSPBPI在癌细胞中的作用将提供可通过定义新的药物发现靶标的信息来开发新疗法的信息。

项目成果

Extracellular HspBP1 inhibits formation of a cytotoxic Tag7-Hsp70 complex in vitro and in human serum.

细胞外 HspBP1 在体外和人血清中抑制细胞毒性 Tag7-Hsp70 复合物的形成。

• DOI: 10.1016/j.biochi.2011.10.007
• 发表时间: 2012
• 期刊: Biochimie
• 影响因子: 3.9
• 作者: Yashin,DenisV;Dukhanina,ElenaA;Kabanova,OlgaD;Romanova,ElenaA;Lukyanova,TamaraI;Tonevitskii,AlexsanderG;Belogurov,AlexeyA;Raynes,DeborahA;Sheludchenkov,AntonA;Gnuchev,NikolaiV;Guerriero,Vince;Georgiev,GeorgiiP;Sashchenko
• 通讯作者: Sashchenko