Department of Immunology, Weizmann Institute of Science , Rehovot , Israel.
Expert Rev Proteomics. 2019 Aug;16(8):711-716. doi: 10.1080/14789450.2019.1651979. Epub 2019 Aug 7.
: Degradation of proteins by cellular proteasomes is critical for the fidelity of protein homeostasis and proper cell function. Indeed, perturbations in proteasome function, as well as the degradation of specific substrates, are associated with a variety of human diseases. Yet, monitoring and analyzing protein degradation in a high throughput manner in physiology and pathology remains limited. : Here we discuss several of the recently developed mass spectrometry-based methods for studying proteasome-mediated cellular degradation and discuss their advantages and limitations. We highlight Mass Spectrometry Analysis of Proteolytic Peptides (MAPP), a method designed to purify and identify proteasome-cleaved cellular proteins as a novel approach in molecular and clinical profiling of human disease. : The recent improvement of proteomics technologies now offers an unprecedented ability to study disease in clinical settings. Expanding clinical studies to include the degradation landscape will provide a new resolution to complement the cellular proteome. In turn, this holds promise to provide both new disease targets and novel peptide biomarkers which will further enhance personalized proteomics.
细胞蛋白酶体对蛋白质的降解对于蛋白质平衡和细胞功能的正常至关重要。事实上，蛋白酶体功能的紊乱以及特定底物的降解与多种人类疾病有关。然而，在生理和病理条件下进行高通量的蛋白质降解监测和分析仍然受到限制。在这里，我们讨论了几种最近开发的基于质谱的方法，用于研究蛋白酶体介导的细胞降解，并讨论了它们的优缺点。我们重点介绍了肽段质谱分析（MAPP）方法，该方法旨在纯化和鉴定蛋白酶体切割的细胞蛋白，作为人类疾病分子和临床分析的一种新方法。最近蛋白质组学技术的改进为在临床环境中研究疾病提供了前所未有的能力。将临床研究扩展到包括降解谱将为补充细胞蛋白质组提供新的分辨率。反过来，这有望提供新的疾病靶点和新的肽类生物标志物，从而进一步增强个性化蛋白质组学。
