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

凋亡抑制蛋白（IAPs）是细胞存活的关键调节因子。考虑到它们的重要作用，从神经退行性疾病到自身免疫和癌症等各种疾病状态都涉及到IAPs水平失调就不足为奇了。IAPs的表达受蛋白质和mRNA合成水平的调控。本研究旨在研究调节IAP家族成员之一（cIAP1）表达的第三种机制——mRNA不稳定性。我们将采用各种生化、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，并确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。我们期望我们的数据将扩展我们对mRNA稳定性调控的总体认识，以及这种调控机制在控制细胞存活中的重要性。我们希望我们的发现将直接转移到理解利用类似机制的其他基因的表达调控。

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.