Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

简介：细胞蛋白酶体降解蛋白质对于蛋白质稳态的保真度和适当的细胞功能至关重要。实际上，蛋白酶体功能的扰动以及特定底物的降解与多种人类疾病有关。然而，在生理学和病理学中以高通量方式监测和分析蛋白质降解仍然是有限的。

涵盖的领域：在这里，我们讨论几种最近开发的基于质谱的方法来研究蛋白酶体介导的细胞降解，并讨论它们的优点和局限性。我们着重介绍蛋白水解肽质谱分析（MAPP），一种旨在纯化和鉴定蛋白酶体切割的细胞蛋白的方法，作为人类疾病的分子和临床概况分析的一种新方法。

专家意见：蛋白质组学技术的最新改进现在提供了在临床环境中研究疾病的空前能力。扩大临床研究以涵盖降解范围将为补充细胞蛋白质组提供新的解决方案。反过来，这有望提供新的疾病靶标和新型肽生物标志物，这将进一步增强个性化蛋白质组学。