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

凋亡抑制蛋白（IAP）是细胞存活的关键调节因子。鉴于其重要作用，IAP的失调水平与从神经退行性疾病到自身免疫和癌症的各种疾病状态有关并不奇怪。IAP的表达在蛋白质和mRNA合成水平上受到调节。该建议涉及研究调节IAP家族成员（cIAP 1）表达的第三种机制- mRNA不稳定性。我们将采用各种生物化学，遗传学和分子生物学技术来确定cIAP 1 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cIAP 1 mRNA稳定性的特定细胞蛋白。我们希望我们的数据将扩展我们的知识的mRNA稳定性的调节，以及这种调节机制在控制细胞存活的重要性。我们希望我们的研究结果将直接转移到了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.