Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.
Nat Commun. 2021 Nov 26;12(1):6778. doi: 10.1038/s41467-021-26842-3.
Protein turnover is critical to cellular physiology as well as to the growth and maintenance of tissues. The unique synthesis and degradation rates of each protein help to define tissue phenotype, and knowledge of tissue- and protein-specific half-lives is directly relevant to protein-related drug development as well as the administration of medical therapies. Using stable isotope labeling and mass spectrometry, we determine the in vivo turnover rates of thousands of proteins-including those of the extracellular matrix-in a set of biologically important mouse tissues. We additionally develop a data visualization platform, named ApplE Turnover, that enables facile searching for any protein of interest in a tissue of interest and then displays its half-life, confidence interval, and supporting measurements. This extensive dataset and the corresponding visualization software provide a reference to guide future studies of mammalian protein turnover in response to physiologic perturbation, disease, or therapeutic intervention.
蛋白质周转对细胞生理学以及组织的生长和维持至关重要。每种蛋白质独特的合成和降解速率有助于定义组织表型,而组织和蛋白质特异性半衰期的知识与蛋白质相关药物的开发以及医学治疗的应用直接相关。使用稳定同位素标记和质谱法,我们确定了一组生物学上重要的小鼠组织中数千种蛋白质(包括细胞外基质蛋白)的体内周转率。我们还开发了一个名为 ApplE Turnover 的数据可视化平台,该平台可方便地在感兴趣的组织中搜索任何感兴趣的蛋白质,并显示其半衰期、置信区间和支持性测量结果。这个广泛的数据集和相应的可视化软件为指导未来研究哺乳动物蛋白质周转对生理扰动、疾病或治疗干预的反应提供了参考。