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

蛋白质之间的相互作用调节基本功能，确保生物体和它们的细胞能够在正确的时间和地点生长和执行任务。许多蛋白质在与其他蛋白质或其他细胞成分(如脂质、DNA或小分子)的复合体中共同作用，以协调共同的功能。与这一提议相关的一组蛋白质需要在每个有机体的每个细胞中制造(或合成)所有新的蛋白质。这些被称为“蛋白质合成因子”。因此，了解蛋白质合成因子是如何发挥作用并相互作用的，对于了解所有细胞、所有生物体中蛋白质是如何合成的是至关重要的。通过改善我们对正常细胞中蛋白质合成等过程的理解，它可以帮助科学家了解这种过程发生变化的疾病。从以前所做的工作中，我们知道蛋白质合成因子的缺陷可能与哺乳动物的一系列疾病有关，如糖尿病、肥胖症，或病毒等感染性病原体如何能够引起感染。蛋白质合成的控制对于生物体对营养缺乏、压力以及胚胎发育(包括组织分化)、神经系统功能(包括记忆)和衰老过程的反应也是至关重要的。在这项提议之前的工作中，我们发现了两个蛋白质合成因子eIF2和eIF5之间的一种新的相互作用，它对蛋白质合成调控至关重要，并描述了eIF5蛋白质的新功能。这项工作定义了启动(或启动)新一轮蛋白质合成所必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的机制产生了影响。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表征它的作用。我们不会使用动物进行这项工作，而是将在试管中使用纯化系统，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。除了进一步加深我们的基本科学知识，我们的发现可能与几个行业直接相关。例如，几种用于治疗严重威胁生命的疾病或生产疫苗的新型先进药物是专门从不同细胞系统制造的蛋白质。了解我们的工作可以帮助最大限度地提高每种产品的产量，从而帮助降低生产成本。

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.