Ubiquitylomics: An Emerging Approach for Profiling Protein Ubiquitylation in Skeletal Muscle

IF 8.9 1区 医学
Samuel O. Lord, Harvey E. Johnston, Rahul S. Samant, Yu-Chiang Lai
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引用次数: 0

Abstract

Skeletal muscle is a highly adaptable tissue, finely tuned by various physiological and pathological factors. Whilst the pivotal role of skeletal muscle in overall health is widely acknowledged, unravelling the underlying molecular mechanisms poses ongoing challenges. Protein ubiquitylation, a crucial post-translational modification, is involved in regulating most biological processes. This widespread impact is achieved through a diverse set of enzymes capable of generating structurally and functionally distinct ubiquitin modifications on proteins. The complexity of protein ubiquitylation has presented significant challenges in not only identifying ubiquitylated proteins but also characterising their functional significance. Mass spectrometry enables in-depth analysis of proteins and their post-translational modification status, offering a powerful tool for studying protein ubiquitylation and its biological diversity: an approach termed ubiquitylomics. Ubiquitylomics has been employed to tackle different perspectives of ubiquitylation, including but not limited to global quantification of substrates and ubiquitin linkages, ubiquitin site recognition and crosstalk with other post-translational modifications. As the field of mass spectrometry continues to evolve, the usage of ubiquitylomics has unravelled novel insights into the regulatory mechanisms of protein ubiquitylation governing biology. However, ubiquitylomics research has predominantly been conducted in cellular models, limiting our understanding of ubiquitin signalling events driving skeletal muscle biology. By integrating the intricate landscape of protein ubiquitylation with dynamic shifts in muscle physiology, ubiquitylomics promises to not only deepen our understanding of skeletal muscle biology but also lay the foundation for developing transformative muscle-related therapeutics. This review aims to articulate how ubiquitylomics can be utilised by researchers to address different aspects of ubiquitylation signalling in skeletal muscle. We explore methods used in ubiquitylomics experiments, highlight relevant literature employing ubiquitylomics in the context of skeletal muscle and outline considerations for experimental design.
泛素组学:剖析骨骼肌中蛋白质泛素化的新方法
骨骼肌是一种适应性很强的组织,会受到各种生理和病理因素的影响而发生微妙的变化。尽管骨骼肌在整体健康中的关键作用已得到广泛认可,但揭示其潜在的分子机制仍是一项持续的挑战。蛋白质泛素化是一种重要的翻译后修饰,参与调节大多数生物过程。这种广泛的影响是通过一系列不同的酶来实现的,这些酶能够对蛋白质进行结构和功能上不同的泛素修饰。蛋白质泛素化的复杂性不仅给泛素化蛋白质的鉴定带来了巨大挑战,也给鉴定其功能意义带来了挑战。质谱技术可对蛋白质及其翻译后修饰状态进行深入分析,为研究蛋白质泛素化及其生物多样性提供了强大的工具:这种方法被称为泛素组学(ubiquitylomics)。泛素组学已被用于从不同角度研究泛素化,包括但不限于底物和泛素连接的全球定量、泛素位点识别以及与其他翻译后修饰的相互影响。随着质谱分析领域的不断发展,泛素组学的应用揭示了蛋白质泛素化对生物学调控机制的新见解。然而,泛素组学研究主要在细胞模型中进行,限制了我们对驱动骨骼肌生物学的泛素信号事件的了解。泛素组学将蛋白质泛素化的复杂情况与肌肉生理学的动态变化结合起来,不仅有望加深我们对骨骼肌生物学的理解,还能为开发肌肉相关的变革性疗法奠定基础。本综述旨在阐明研究人员如何利用泛素组学来解决骨骼肌中泛素化信号的不同方面问题。我们探讨了泛素组学实验中使用的方法,重点介绍了在骨骼肌中使用泛素组学的相关文献,并概述了实验设计的注意事项。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Cachexia, Sarcopenia and Muscle
Journal of Cachexia, Sarcopenia and Muscle Medicine-Orthopedics and Sports Medicine
自引率
12.40%
发文量
0
期刊介绍: The Journal of Cachexia, Sarcopenia, and Muscle is a prestigious, peer-reviewed international publication committed to disseminating research and clinical insights pertaining to cachexia, sarcopenia, body composition, and the physiological and pathophysiological alterations occurring throughout the lifespan and in various illnesses across the spectrum of life sciences. This journal serves as a valuable resource for physicians, biochemists, biologists, dieticians, pharmacologists, and students alike.
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