Issue 13, 2020

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

Abstract

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.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
20 Dec 2019
Accepted
09 Mar 2020
First published
10 Mar 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2020,11, 3557-3568

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

M. Tong, J. M. Smeekens, H. Xiao and R. Wu, Chem. Sci., 2020, 11, 3557 DOI: 10.1039/C9SC06479F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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