Regulation of protein synthesis by oxidative stress in yeast

所有的有机体都必须对其外部环境的变化做出反应。随着基因组序列的获得，越来越多的注意力集中在分析这些适应性反应过程中基因表达/转录谱的变化。信使核糖核酸到蛋白质的翻译是基因表达途径的基本组成部分。然而，关于翻译控制机制在应激反应中的作用，人们知之甚少，这也是本研究的重点。我们的初步数据表明，酵母中的蛋白质合成在过氧化氢胁迫下被迅速和可逆地抑制。然而，矛盾的是，某些mRNAs抵抗抑制，并在应激条件下继续被翻译。我们的数据表明，翻译起始因子2(EIF2)在氧化应激反应中被磷酸化。在所有真核生物中，eIF2是翻译调控的焦点。在过去，大多数工作都集中在介导eIF2磷酸化的激酶上。在目前的工作计划中，我们将研究eIF2的磷酸化和去磷酸化。这对于理解蛋白质合成的协调调节是至关重要的，因为蛋白质合成是对氧化应激的反应。

All organisms must respond to changes in their external environment. With the availability of genome sequences much attention has focused on analyzing the changes in gene expression/transcription profiles during these adaptive responses. The translation of mRNA into protein is a fundamental component of the gene expression pathway. However, relatively little is known regarding the role of translational control mechanisms in the response to stress conditions, which is the focus of this proposed study. Our preliminary data have shown that protein synthesis in yeast is rapidly and reversibly inhibited in response to hydrogen peroxide stress. Paradoxically however, certain mRNAs are resistant to inhibition and continue to be translated during stress conditions. Our data show that translation initiation factor 2 (eIF2) is phosphorylated in response to oxidative stress. eIF2 serves as a focus for translational regulation in all eukaryotic species. In the past, most work has focused on the kinases which mediate phosphorylation of eIF2. In this current work programme, we will study both the phosphorylation and dephosphorylation of eIF2. This is critical in order to understand the co-ordinated regulation of protein synthesis that is observed in response to oxidative stress.