Regulation of protein synthesis by oxidative stress in yeast

酵母中氧化应激对蛋白质合成的调节

• 批准号: BB/E00623X/1
• 负责人: Christopher Grant
• 金额: $ 46.57万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE00623X%2F1
• 关键词: Regulation; protein; synthesis; oxidative; stress

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.

所有生物都必须对外部环境的变化做出反应。随着基因组序列的可用性，人们的注意力集中在分析这些适应性反应过程中基因表达/转录谱的变化上。mRNA翻译成蛋白质是基因表达途径的基本组成部分。然而，相对知之甚少的翻译控制机制在应激条件下，这是本研究的重点反应的作用。我们的初步数据表明，酵母中的蛋白质合成是快速和可逆的抑制反应过氧化氢应激。然而，奇怪的是，某些mRNA对抑制具有抗性，并且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（eIF 2）是磷酸化的氧化应激反应。eIF 2在所有真核生物中作为翻译调控的焦点。在过去，大多数工作集中在介导eIF 2磷酸化的激酶上。在目前的工作计划中，我们将研究eIF 2的磷酸化和去磷酸化。这是至关重要的，以了解在氧化应激反应中观察到的蛋白质合成的协调调节。