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

N-末端乙酰化作为蛋白质降解信号控制植物发育和胁迫反应

• 批准号: BB/M020568/1
• 负责人: Daniel Gibbs
• 金额: $ 51.92万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM020568%2F1
• 关键词: terminal; acetylation; signal; protein; degradation

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.

与动物不同，植物不能移动，因此进化为在不断变化的环境中生长和生存。如果我们要发展上级作物，生产足够的食物来支持面临气候变化的全球人口增长，那么了解植物用于实现这一目标的机制至关重要。植物控制其生长并对环境做出反应的一种方式是通过调节其细胞中蛋白质的稳定性-植物需要精确控制何时摆脱蛋白质，以便成功快速地对各种信号做出反应。植物中的蛋白质降解（蛋白质水解）对于控制植物生命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（例如光和氧气）的感知和响应都依赖于蛋白质降解。因此，提高我们对蛋白质稳定性调节信号和机制的理解是植物科学的一个主要焦点，以确定植物育种家和生物技术家可以关注的目标，以开发改良的作物品种。这项工作将确定和表征植物中靶向蛋白质降解的新途径。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起始端（N-末端）添加小分子（乙酰基）而启动的。一旦蛋白质被N-末端乙酰化，它就可以被另一种类型的蛋白质识别，这种蛋白质添加了第二个标记（泛素），作为细胞降解的信号。我们的初步研究表明，蛋白质降解通过这条途径在植物发育和胁迫响应（包括种子萌发，干旱响应和叶绿素含量的控制）中发挥重要作用。因此，这条途径代表了一个有前途的新系统，了解和操纵植物的生长和生存，未来粮食安全的一个关键焦点。我们将详细研究这条途径是如何发挥作用的，以及它控制植物生命的哪些重要方面。研究将在植物拟南芥中进行-植物世界的“实验室老鼠”-因为与作物物种相比，它更容易生长和研究，但具有相同的基因和机制。我们将开发和分析已经去除了该途径的关键成分（突变体）的拟南芥植物以及“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发挥的作用。我们还将进行研究，看看这条途径在植物中的工作，无论是空间（即叶与根？）在生命周期中，随着时间的推移。总的来说，这将使我们能够剖析这种途径在何时何地发挥作用，并确定它调节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-乙酰化和随后加入的泛素，这将为通过该途径支持蛋白质水解的机制和信号提供重要的见解，并有助于指导未来的研究，以确定天然蛋白质的目标。这一新的途径的功能特性将大大提高我们对植物信号转导的理解和行为。由于这些基因在重要的作物物种中是保守的-从大麦到西兰花-因此这项研究将有助于为未来的研究提供信息，以创造更好，更高效的作物品种。除了揭示一种全新的调节植物蛋白质稳定性的机制外，这项工作还将为为什么一些蛋白质在其N-末端被乙酰化提供新的见解。这种修饰在植物和动物中广泛保守，最近与人类疾病有关，但其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的见解，也可能有利于人类和医学研究。

项目成果

The PRT6 N-degron pathway restricts VERNALIZATION 2 to endogenous hypoxic niches to modulate plant development.

• DOI: 10.1111/nph.16477
• 发表时间: 2021-01
• 期刊: The New phytologist
• 作者: Labandera AM;Tedds HM;Bailey M;Sprigg C;Etherington RD;Akintewe O;Kalleechurn G;Holdsworth MJ;Gibbs DJ
• 通讯作者: Gibbs DJ

Emerging Functions for N-Terminal Protein Acetylation in Plants.

• DOI: 10.1016/j.tplants.2015.08.008
• 发表时间: 2015-10
• 期刊: Trends in plant science
• 影响因子: 20.5
• 作者: Gibbs DJ

The Arabidopsis NOT4A E3 ligase promotes PGR3 expression and regulates chloroplast translation.

• DOI: 10.1038/s41467-020-20506-4
• 发表时间: 2021-01-11
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Bailey M;Ivanauskaite A;Grimmer J;Akintewe O;Payne AC;Osborne R;Labandera AM;Etherington RD;Rantala M;Baginsky S;Mulo P;Gibbs DJ
• 通讯作者: Gibbs DJ

Nt-acetylation-independent turnover of SQUALENE EPOXIDASE 1 by Arabidopsis DOA10-like E3 ligases.

拟南芥doa10样E3连接酶对小乙烯环氧酶1的NT-乙酰化非依赖性周转。

• DOI: 10.1093/plphys/kiad406
• 发表时间: 2023-10-26
• 期刊: PLANT PHYSIOLOGY
• 影响因子: 7.4
• 作者: Etherington, Ross D.;Bailey, Mark;Boyer, Jean-Baptiste;Armbruster, Laura;Cao, Xulyu;Coates, Juliet C.;Meinnel, Thierry;Wirtz, Markus;Giglione, Carmela;Gibbs, Daniel J.
• 通讯作者: Gibbs, Daniel J.

The Arabidopsis NOT4A E3 ligase coordinates PGR3 expression to regulate chloroplast protein translation

• DOI: 10.1101/2020.04.02.021998
• 发表时间: 2020-04
• 期刊: bioRxiv
• 作者: Mark Bailey;Aiste Ivanauskaite;Julia Grimmer;Oluwatunmise Akintewe;Adrienne C. Payne;Ross D. Etherington;A. Labandera;Rory Osborne;Marjaana Rantala;S. Baginsky;P. Mulo;D. Gibbs