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Systematic quantification of the dynamics of newly synthesized proteins unveiling their degradation pathways in human cells

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...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2020-04, Vol.11 (13), p.3557-3568
Main Authors: Tong, Ming, Smeekens, Johanna M, Xiao, Haopeng, Wu, Ronghu
Format: Article
Language:English
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Summary: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.
ISSN:2041-6520
2041-6539
DOI:10.1039/c9sc06479f