Role of translation elongation factor 1B (eEF1B) in regulating protein synthesis in response to oxidative stress in yeast

翻译延伸因子 1B (eEF1B) 在调节酵母氧化应激蛋白质合成中的作用

• 批准号: BB/F011016/1
• 负责人: Christopher Grant
• 金额: $ 49.27万
• 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: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF011016%2F1
• 关键词: Role; translation; elongation; factor; 1B

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. This application is based on our preliminary findings showing that oxidative stress causes a rapid inhibition of protein synthesis. Such a global inhibition of protein synthesis is widely recognised as a response of biological systems to stress conditions. Preventing protein synthesis during stress conditions may allow time for organisms to direct gene expression towards the production of new molecules required to protect against or detoxify the stress. Our data show that oxidative stress inhibits protein synthesis at multiple levels. The goal of this comprehensive research programme is to understand the molecular details of these regulatory mechanisms. This study will focus on oxidative stress which is a major problem for most biological systems. Reactive oxygen species and free radicals are produced as toxic by-products of normal metabolism and through exposure to environmental factors including sunlight. All organisms, including humans, contain effective antioxidants such as vitamins A and C and enzymes, such as catalase and superoxide dismutase, that can detoxify these harmful molecules. However, under extreme conditions reactive oxygen species can overwhelm the antioxidant defences resulting in a so-called 'oxidative stress'. It is important to understand how cells respond to an oxidative stress because it is implicated in many diseases including cancer, neurodegenerative and cardiovascular diseases. In addition, oxidative damage to cells and tissues can contribute to the decline in physiological function that occurs in ageing cells. This research will make use of the yeast Saccharomyces cerevisiae as a model organism. Yeast offers an ideal model system to study these types of processes since it is genetically tractable and has served as the organism of choice for most post-genomic studies. There is also a high degree of conservation between the stress-protective systems in yeast and human cells making it an ideal organism for this study.

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。这项应用是基于我们的初步研究结果表明，氧化应激导致蛋白质合成的快速抑制。蛋白质合成的这种全面抑制被广泛认为是生物系统对应激条件的反应。在胁迫条件下阻止蛋白质合成可以使生物体有时间将基因表达导向生产保护免受胁迫或解毒所需的新分子。我们的数据表明，氧化应激在多个水平上抑制蛋白质合成。这项综合研究计划的目标是了解这些调控机制的分子细节。这项研究将集中在氧化应激，这是大多数生物系统的主要问题。活性氧和自由基是正常代谢的有毒副产品，并通过暴露于环境因素，包括阳光。包括人类在内的所有生物体都含有有效的抗氧化剂，如维生素A和C以及酶，如过氧化氢酶和超氧化物歧化酶，可以消除这些有害分子的毒性。然而，在极端条件下，活性氧可以压倒抗氧化剂防御，导致所谓的“氧化应激”。重要的是要了解细胞如何对氧化应激作出反应，因为它涉及许多疾病，包括癌症，神经退行性疾病和心血管疾病。此外，对细胞和组织的氧化损伤可能导致衰老细胞中发生的生理功能下降。本研究将利用酿酒酵母作为模式生物。酵母为研究这些类型的过程提供了理想的模型系统，因为它在遗传上易于处理，并且已成为大多数后基因组研究的首选生物体。酵母和人类细胞中的应激保护系统之间也存在高度的保守性，使其成为本研究的理想生物体。