N-terminal acetylation as a signal for protein degradation controlling plant development and stress responses

与动物不同，植物不能移动，因此进化成能在不断变化的环境中生长和生存。如果我们要发展优势作物，以生产足够的粮食来养活日益增长的全球人口，面对气候变化，了解植物用于实现这一目标的机制是至关重要的。植物控制生长和对环境做出反应的一种方式是通过调节细胞中蛋白质的稳定性-植物需要精确控制何时去除蛋白质，以便成功和快速地对广泛的信号做出反应。植物中的蛋白质降解(蛋白质降解)对于控制植物生活的几乎所有方面都很重要--例如，对大多数植物激素和大量外部和内部信号(如光和氧)的感知和响应都依赖于蛋白质的降解。因此，提高对蛋白质稳定性调控信号和机制的了解是植物科学的一个主要焦点，以确定植物育种者和生物技术工作者可以专注于开发改良作物品种的靶标。这项工作将识别和表征一条在植物中靶向降解蛋白质的新途径。在最近首次在酵母中发现的这一途径中，降解是通过在蛋白质的开始(N-末端)添加一个小分子(乙酰基)来启动的。一旦一种蛋白质被N-末端乙酰化，它就可以被另一种类型的蛋白质识别，这种蛋白质增加了第二个标记(泛素)，作为细胞降解的信号。我们的初步研究表明，通过这一途径进行的蛋白质降解在植物发育和逆境反应(包括控制种子萌发、干旱反应和叶绿素含量)中发挥着重要作用。因此，这一途径代表了一种很有前途的新系统，用于理解和操纵植物的生长和生存，这是未来粮食安全的关键焦点。我们将详细研究这一途径的功能及其控制植物生命的哪些重要方面。研究将在植物拟南芥--植物世界的“实验室老鼠”--中进行，因为与农作物物种相比，拟南芥更容易种植和研究，但它拥有所有相同的基因和机制。我们将开发和分析已经移除了这一途径的关键成分的拟南芥植物(突变体)和过度生产它们的植物，以了解这些因素在正常生长和发育过程中所起的作用。我们还将进行研究，以了解这种途径在植物中的哪里发挥作用，无论是在空间上(即叶还是根？)在生命周期中随着时间的推移。总而言之，这将使我们能够剖析这条途径在何时何地发挥作用，并确定它调控植物生命的哪些关键方面。我们还将对该途径的蛋白质靶标进行生化分析，以表明它们的降解依赖于NT-乙酰化和随后泛素的添加，这将为通过这一途径进行蛋白质分解的机制和信号提供重要的见解，并有助于指导未来识别天然蛋白质靶标的研究。这一新途径的功能特征将极大地增强我们对植物信号和行为的理解。由于这些基因在从大麦到西兰花的重要作物物种中都是保守的，因此这项研究将有助于为未来创造更好、更有效的作物品种的研究提供信息。除了揭示一种全新的调节植物蛋白质稳定性的机制外，这项工作还将为一些蛋白质在N端乙酰化的原因提供新的见解。这种修饰在植物和动物中广泛保守，最近被认为与人类疾病有关，但它的功能在很大程度上是未知的。因此，我们的详细研究将提供科学见解，也可能有利于人类和医学研究。

Unlike animals, plants cannot move, and have therefore evolved to grow and survive in constantly changing environments. Understanding the mechanisms that plants use to achieve this is critical if we are to develop superior crops to produce enough food to support a growing global population in the face of climate change. One way in which plants control their growth and respond to the environment is by regulating the stability of the proteins in their cells - plants need to precisely control when to get rid of a protein in order to successfully and rapidly respond to a wide range of signals. Protein degradation (proteolysis) in plants is important for controlling almost all aspects of plant life - for example, the sensing of and response to most plant hormones and a large number of external and internal signals (e.g. light and oxygen) is reliant on protein degradation. Therefore, increasing our understanding of the signals and mechanisms regulating protein stability is a major focus for plant science in order to identify targets that plant breeders and biotechnologists can focus on to develop improved crop varieties.This work will identify and characterize a new pathway for targeted protein degradation in plants. In this pathway, which was recently identified for the first time in yeast, degradation is initiated through the addition of a small molecule (acetyl) at the beginning (N-terminus) of a protein. Once a protein has been N-terminally acetylated, it can then be recognised by another type of protein that adds a second marker (ubiquitin), which acts as a signal for degradation by the cell. Our initial studies suggest that protein degradation via this pathway plays important roles during plant development and stress response (including the control of seed germination, drought response and chlorophyll content). This pathway therefore represents a promising new system for understanding and manipulating plant growth and survival, a key focus for future food security.We will investigate in detail how this pathway functions and what important aspects of plant life it controls. Studies will be carried out in the plant Arabidopsis - the 'lab rat' of the plant world - since it is much easier to grow and study compared to crop species, yet has all the same genes and mechanisms. We will develop and analyse Arabidopsis plants that have had the key components of this pathway removed (mutants) and ones which 'over produce' them, in order to understand what roles these factors play during normal growth and development. We will also perform studies to see where this pathway is working in the plant, both spatially (i.e. leaves vs roots?) and over time during the life cycle. Collectively this will allow us to dissect where and when this pathway is functional, and identify what key aspects of plant life it regulates. We will also perform biochemical analyses on protein 'targets' of the pathway, to show that their degradation is dependent on Nt-acetylation and subsequent addition of ubiquitin, which will provide important insight into the mechanisms and signals underpinning proteolysis via this pathway, and help guide future studies into identifying natural protein targets.Functional characterization of this novel pathway will greatly enhance our understanding of plant signalling and behaviour. Since these genes are conserved in important crop species - from barley to broccoli - this research will therefore help inform future studies into creating better, more efficient crop varieties. As well as uncovering an entirely new mechanism for regulating protein stability in plants, this work will also provide new insight into why some proteins are acetylated at their N-terminus. This modification is widely conserved in plants and animals, and was recently linked to human disease, but its functions are largely unknown. Thus our detailed studies will provide scientific insight that may also benefit human and medical research.