Systematic quantification of the dynamics of newly synthesized proteins unveiling their degradation pathways in human cells.
Systematic quantification of the dynamics of newly synthesized proteins unveiling their degradation pathways in human cells.
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DOI：
10.1039/c9sc06479f
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发表时间：
2020-03-10
期刊：
影响因子：
8.4
通讯作者：
Wu R
中科院分区：
文献类型：
--
作者：
Tong M;Smeekens JM;Xiao H;Wu R
蛋白质在细胞生长和增殖过程中不断合成。同时，过量和错误折叠的蛋白质必须被降解，否则它们会成为细胞的负担。蛋白质降解对于维持细胞中的蛋白质稳态是必不可少的，并且蛋白质降解系统的功能障碍导致许多疾病，例如癌症和神经退行性疾病。尽管蛋白质降解的重要性，许多蛋白质的降解途径仍有待探索。在这里，我们通过整合代谢标记、点击化学和多重蛋白质组学，全面研究了人类细胞中新合成蛋白质的降解，并对新合成蛋白质进行了系统和定量分析，首次揭示了许多蛋白质的降解途径。生物信息学分析表明，通过两种主要途径降解的蛋白质具有不同的性质和功能。通过泛素-蛋白酶体途径降解的蛋白质含有更多的无序结构，而通过自噬-溶酶体途径降解的蛋白质具有显著更高的疏水性。对新合成蛋白质动力学的系统和定量研究提供了关于蛋白质降解的前所未有的有价值的信息，这导致对蛋白质性质和细胞活性的更好理解。对新合成蛋白质动力学的系统定量首先揭示了许多蛋白质在人类细胞中的降解途径，并且通过两种主要途径中的每一种降解的蛋白质具有不同的性质和功能。
Proteins are continuously synthesized during cell growth and proliferation. At the same time, excessive and misfolded proteins have to be degraded, otherwise they are a burden to cells. Protein degradation is essential to maintain proteostasis in cells, and dysfunction of protein degradation systems results in numerous diseases such as cancer and neurodegenerative diseases. Despite the importance of protein degradation, the degradation pathways of many proteins remain to be explored. Here, we comprehensively investigated the degradation of newly synthesized proteins in human cells by integrating metabolic labeling, click chemistry, and multiplexed proteomics, and systematic and quantitative analysis of newly synthesized proteins first revealed the degradation pathways of many proteins. Bioinformatic analysis demonstrates that proteins degraded through two major pathways have distinct properties and functions. Proteins degraded through the ubiquitin-proteasome pathway contain more disordered structures, whereas those through the autophagy-lysosome pathway have significantly higher hydrophobicity. Systematic and quantitative investigation of the dynamics of newly synthesized proteins provides unprecedented and valuable information about protein degradation, which leads to a better understanding of protein properties and cellular activities. Systematic quantification of the dynamics of newly synthesized proteins first reveals the degradation pathways of many proteins in human cells, and proteins degraded through each of the two major pathways have distinct properties and functions.
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影响因子：
46.2
作者：
Jewett JC;Bertozzi CR
通讯作者：
Bertozzi CR
影响因子：
64.5
作者：
Huttlin EL;Jedrychowski MP;Elias JE;Goswami T;Rad R;Beausoleil SA;Villén J;Haas W;Sowa ME;Gygi SP
通讯作者：
Gygi SP
影响因子：
8.4
作者：
Chen W;Smeekens JM;Wu R
通讯作者：
Wu R
影响因子：
9.2
作者：
Lam, Yun Wah;Lamond, Angus I.;Mann, Matthias;Andersen, Jens S.
通讯作者：
Andersen, Jens S.
影响因子：
7.4
作者：
Clark, David J.;Hu, Yingwei;Zhang, Hui
通讯作者：
Zhang, Hui