Translational control of gene expression and the choice between cell death and proliferation

蛋白质在细胞中执行大多数酶和结构功能。因此，在给定细胞中发现的蛋白质分子的种类决定了其特征，细胞通过调整其集合中某些或许多蛋白质的丰度来响应其环境的变化。蛋白质组装的指令编码在基因中，这些信息通过称为信使（m）RNA的中间分子表达。基因转录成mRNA分子和随后由核糖体翻译成蛋白质都是基因表达途径中严格控制的步骤。错误的基因表达是人类疾病的一个主要因素，翻译失调与越来越多的疾病有关，如癌症和心血管疾病、病毒感染和不太常见的遗传综合征。这里提出的项目是由翻译调节在控制细胞死亡和存活之间的平衡中的作用的新证据所推动的。打破这种平衡会给生物体带来灾难性的后果，这一点可以从它参与许多重大疾病中得到证明。G.中风、心力衰竭、神经变性、AIDS、癌症、自身免疫）。我们的目的是测试的假设，一个假定的翻译调节称为p97-DAP 5-NAT 1，和一个专门的翻译起始机制，内部核糖体进入是重要的，维持这种平衡。为了研究这一点，我们将使用DNA芯片，这是基因组学研究的一种新工具，可以在一个实验中测量数千个mRNA分子的水平。可以想象，这些特殊的翻译机制的知识将导致治疗干预的新目标，这项工作将有助于一些实验工具，以探索这些途径在未来。

Proteins carry out most enzymatic and structural functions in a cell. Thus, the kinds of protein molecules that are found in a given cell determine its characteristics and cells respond to changes in their environment by adjusting the abundance of some or many proteins in their collection. The instructions for the assembly of proteins are encoded in the genes and this information is expressed via intermediary molecules called messenger (m)RNA. Both, transcription of the genes into mRNA molecules and their subsequent translation by the ribosomes into protein are tightly controlled steps in the gene expression pathway. Erroneous gene expression is a major factor in human disease and dysregulation of translation is linked to a growing spectrum of illnesses such as cancer and cardiovascular disease, viral infection, and less frequent hereditary syndromes. The project proposed here is prompted by emerging evidence for a role of translational regulation in controlling the balance between cell death and survival. Tipping this balance has disastrous consequences for an organism as evidenced by its involvement in many major disorders (e. g. stroke, heart failure, neurodegeneration, AIDS, cancer, autoimmunity). Our aim is to test the hypothesis that a putative translational regulator termed p97-DAP5-NAT1, and a specialised mechanism of translation initiation by internal ribosome entry are important for the maintenance of this balance. To investigate this, we will employ DNA chips, a novel tool from Genomics research that allows the measurement of the levels of thousands of mRNA molecules in a single experiment. It is conceivable that knowledge of these special mechanisms of translation will lead to novel targets for therapeutic intervention, and this work will contribute some of the experimental tools to explore these avenues in the future.