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Eukaryotic initiation factor 5 guanine-nucleotide dissociation inhibitor activity and control of translation initiation

真核起始因子 5 鸟嘌呤核苷酸解离抑制剂活性和翻译起始控制

基本信息

批准号：
BB/H010599/1
负责人：
Graham Pavitt
金额：
$ 42.23万
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：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH010599%2F1
关键词：
Eukaryotic initiation factor guanine nucleotide

项目摘要

Interactions between proteins modulate essential functions, ensuring that organisms and their cells can grow and perform tasks at the correct time and place. Many proteins act together within complexes either with other proteins or also with other cell components (lipids, DNA or small molecules for example) to coordinate a common function. One group of proteins relevant to this proposal is required make (or synthesize) all new proteins in each cell in every organism. These are called 'protein synthesis factors'. Understanding how protein synthesis factors function and interact with each other is, therefore, fundamental to understanding how proteins are made in all cells, in all organisms. By improving our understanding how processes such as protein synthesis work in normal cells it can help scientists understand diseases in which this process is altered. From previous work done we know that defects in protein synthesis factors can be associated with a wide range of diseases in mammals such as forms of diabetes, obesity, or how infectious agents such as viruses are able to cause infections. Control of protein synthesis is also critical for organism responses to nutrient deprivation, stress, as a well as during embryo development including differentiation of tissues, for nervous system function including memory, and during the aging process. In work leading up to this proposal we identified a novel interaction between two protein synthesis factors known as eIF2 and eIF5 that is critical for protein synthesis regulation and describes a new function for the eIF5 protein. This work has defined a new step in the chain of events necessary for starting (or initiating) new rounds of protein synthesis. By discovering this new step, it has implications for how scientists understand the mechanisms of protein synthesis control. We now have a leading advantage, as we are the first researchers to uncover this. We propose here a set of detailed molecular experiments to characterise its role. Rather than using animals for this work, we will use purified systems in test tubes and perform some experiments in yeast cells which are an excellent cellular model system to study universal translational controls common to all forms of life. In addition to furthering our basic science knowledge, our findings may be directly relevant to several industries. For example, several new advanced medicines used to treat serious life-threatening diseases, or produce vaccines are proteins made specifically from different cell systems. Knowledge of our work could help maximize the production of each product, thereby helping to reduce costs of production.

蛋白质之间的相互作用调节基本功能，确保生物体及其细胞能够在正确的时间和地点生长和执行任务。许多蛋白质在复合物中与其他蛋白质或其他细胞成分（例如脂质，DNA或小分子）一起起作用，以协调共同的功能。与此相关的一组蛋白质需要在每个生物体的每个细胞中制造（或合成）所有新蛋白质。这些被称为“蛋白质合成因子”。因此，了解蛋白质合成因子的功能和相互作用是了解蛋白质如何在所有细胞中，在所有生物体中产生的基础。通过提高我们对蛋白质合成等过程在正常细胞中如何工作的理解，它可以帮助科学家了解这一过程被改变的疾病。从以前的工作中，我们知道蛋白质合成因子的缺陷可能与哺乳动物中的各种疾病有关，如糖尿病，肥胖症，或者病毒等传染性因子如何引起感染。蛋白质合成的控制对于生物体对营养缺乏、压力的反应以及在胚胎发育期间（包括组织分化）、对于神经系统功能（包括记忆）和在衰老过程期间也是至关重要的。在导致这一提议的工作中，我们确定了两种蛋白质合成因子eIF2和eIF5之间的新相互作用，这对蛋白质合成调控至关重要，并描述了eIF5蛋白的新功能。这项工作定义了启动（或启动）新一轮蛋白质合成所需的事件链中的新步骤。通过发现这一新步骤，它对科学家如何理解蛋白质合成控制机制具有重要意义。我们现在拥有领先优势，因为我们是第一批发现这一点的研究人员。我们在这里提出了一套详细的分子实验来验证它的作用。我们将使用试管中的纯化系统，而不是使用动物进行这项工作，并在酵母细胞中进行一些实验，酵母细胞是研究所有生命形式共同的通用翻译控制的优秀细胞模型系统。除了促进我们的基础科学知识，我们的研究结果可能与几个行业直接相关。例如，用于治疗严重危及生命的疾病或生产疫苗的几种新型先进药物都是由不同细胞系统专门制成的蛋白质。了解我们的工作有助于最大限度地提高每种产品的产量，从而有助于降低生产成本。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mechanisms of translational regulation by a human eIF5-mimic protein.

DOI：
10.1093/nar/gkr339
发表时间：
2011-10
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Singh CR;Watanabe R;Zhou D;Jennings MD;Fukao A;Lee B;Ikeda Y;Chiorini JA;Campbell SG;Ashe MP;Fujiwara T;Wek RC;Pavitt GD;Asano K
通讯作者：
Asano K

eIF5 is a dual function GAP and GDI for eukaryotic translational control.