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与其他细胞成分（如脂质、DNA或小分子）协同作用，以协调共同的功能。需要一组与此建议相关的蛋白质在每个生物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如何发挥作用并相互作用，是了解所有细胞、所有生物体中蛋白质如何产生的基础。通过提高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的多种疾病有关，如糖尿病、肥胖症，或病毒等传染性病原体如何引起感染。蛋白质合成的控制对于生物体对营养剥夺、应激的反应以及胚胎发育（包括组织分化）、神经系统功能（包括记忆）和衰老过程也至关重要。在提出这一建议的工作中，我们发现了两种蛋白质合成因子eIF2和eIF5之间的一种新的相互作用，这种相互作用对蛋白质合成调控至关重要，并描述了eIF5蛋白的新功能。这项工作在开始（或启动）新一轮蛋白质合成所需的事件链中定义了一个新的步骤。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。我们现在有一个领先的优势，因为我们是第一个发现这一点的研究人员。我们在这里提出一套详细的分子实验来描述它的作用。我们将在试管中使用纯化系统，并在酵母细胞中进行一些实验，而不是在动物身上进行这项工作，酵母细胞是一种很好的细胞模型系统，可以研究所有生命形式共同的普遍翻译控制。除了进一步提高我们的基础科学知识，我们的发现可能与几个行业直接相关。例如，用于治疗严重威胁生命的疾病或生产疫苗的几种新的先进药物是由不同细胞系统专门制成的蛋白质。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，从而有助于降低生产成本。

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.