The role of RNA instability determinants in the regulation of cIAP1 expression

RNA不稳定决定因素在cIAP1表达调节中的作用

• 批准号: 250100-2010
• 负责人: Holcik, Martin
• 金额: $ 2.4万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=455569
• 关键词: role; RNA; instability; determinants; regulation

The Inhibitor of Apoptosis proteins (IAPs) are critical regulators of cell survival. Given their important role it is not surprising that dysregulated levels of IAPs are implicated in various disease states ranging from neurodegenerative disorders to autoimmunity and cancer. The expression of IAPs is regulated at both the level of protein and mRNA synthesis. This proposal deals with investigating a third mechanism regulating one members of the IAP family (cIAP1) expression - mRNA instability. We will employ various biochemical, genetic and molecular biology techniques to define the determinants of RNA stability in the cIAP1 mRNA and to identify specific cellular proteins that bind to these determinants and regulate cIAP1 mRNA stability. We expect that our data will extend our knowledge of the regulation of mRNA stability in general as well as the importance of this regulatory mechanism in the control of cell survival. We hope that our findings will be directly transferable to understanding regulation of expression of other genes that utilize similar mechanism.

细胞凋亡抑制蛋白(IAPs)是细胞存活的重要调节因子。鉴于IAP的重要作用，IAP水平失调与从神经退行性疾病到自身免疫和癌症等各种疾病状态有关也就不足为奇了。IAPs的表达在蛋白质和mRNA合成水平上都受到调控。这项建议涉及到研究第三种调节IAP家族成员之一(CIAP1)表达的机制-mRNA不稳定性。我们将使用各种生化、遗传和分子生物学技术来确定cIAP1 mRNA中RNA稳定性的决定因素，并鉴定与这些决定因素结合并调节cIAP1 mRNA稳定性的特定细胞蛋白。我们希望，我们的数据将扩大我们的知识，一般调控的信使核糖核酸的稳定性，以及这一调控机制的重要性，控制细胞的生存。我们希望我们的发现将直接用于理解其他利用类似机制的基因的表达调控。