Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, Egypt.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
J Neurochem. 2019 Nov;151(4):520-533. doi: 10.1111/jnc.14838. Epub 2019 Aug 25.
Protein degradation is a crucial regulatory process in maintaining cellular proteostasis. The selective degradation of intracellular proteins controls diverse cellular and biochemical processes in all kingdoms of life. Targeted protein degradation is implicated in controlling the levels of regulatory proteins as well as eliminating misfolded and any otherwise abnormal proteins. Deregulation of protein degradation is concomitant with the progression of various neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Thus, methods of measuring metabolic half-lives of proteins greatly influence our understanding of the diverse functions of proteins in mammalian cells including neuronal cells. Historically, protein degradation rates have been studied via exploiting methods that estimate overall protein degradation or focus on few individual proteins. Notably, with the recent technical advances and developments in proteomic and imaging techniques, it is now possible to measure degradation rates of a large repertoire of defined proteins and analyze the degradation profile in a detailed spatio-temporal manner, with the aim of determining proteome-wide protein stabilities upon different physiological conditions. Herein, we discuss some of the classical and novel methods for determining protein degradation rates highlighting the crucial role of some state of art approaches in deciphering the global impact of dynamic nature of targeted degradation of cellular proteins. This article is part of the Special Issue "Proteomics".
蛋白质降解是维持细胞内蛋白质稳定的一个关键调节过程。在所有生命领域中，细胞内蛋白质的选择性降解控制着多样化的细胞和生化过程。靶向蛋白质降解与调节蛋白水平的控制以及消除错误折叠和任何其他异常蛋白质有关。蛋白质降解的失调与各种神经退行性疾病（如帕金森病和阿尔茨海默病）的进展同时发生。因此，测量蛋白质代谢半衰期的方法极大地影响了我们对哺乳动物细胞（包括神经元细胞）中蛋白质多样化功能的理解。从历史上看，通过利用估计整体蛋白质降解或专注于少数个别蛋白质的方法来研究蛋白质降解率。值得注意的是，随着蛋白质组学和成像技术的最新技术进步和发展，现在可以测量大量定义蛋白质的降解率，并以详细的时空方式分析降解谱，旨在确定不同生理条件下蛋白质组范围内蛋白质的稳定性。本文讨论了一些经典和新颖的方法来确定蛋白质降解率，重点介绍了一些最先进的方法在解析细胞蛋白质靶向降解的动态性质的全局影响方面的关键作用。本文是“蛋白质组学”特刊的一部分。
