Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates

Molecular Cell
Andrea Brigitta AlberDavid M Suter

Abstract

Cells need to reliably control their proteome composition to maintain homeostasis and regulate growth. How protein synthesis and degradation interplay to control protein expression levels remains unclear. Here, we combined a tandem fluorescent timer and pulse-chase protein labeling to disentangle how protein synthesis and degradation control protein homeostasis in single live mouse embryonic stem cells. We discovered substantial cell-cycle dependence in protein synthesis rates and stabilization of a large number of proteins around cytokinesis. Protein degradation rates were highly variable between cells, co-varied within individual cells for different proteins, and were positively correlated with synthesis rates. This suggests variability in proteasome activity as an important source of global extrinsic noise in gene expression. Our approach paves the way toward understanding the complex interplay of synthesis and degradation processes in determining protein levels of individual mammalian cells.

Citations

Mar 26, 2019·Cell Cycle·Andrea Brigitta Alber, David Michael Suter
Jul 30, 2019·Journal of Neurochemistry·Mohamed A EldeebRichard P Fahlman
Sep 27, 2019·Molecular Systems Biology·Daniel StrebingerDavid M Suter
Feb 6, 2020·Chembiochem : a European Journal of Chemical Biology·Yonatan G MideksaMatthias J Feige
Oct 4, 2019·Nature Communications·Elisa PedoneLucia Marucci
Dec 16, 2018·The Journal of Cell Biology·Brandon H ToyamaMartin W Hetzer
Feb 1, 2019·Nature Communications·Mahé RaccaudDavid M Suter
Apr 2, 2020·Molecular and Cellular Biology·Justin H LayerUtpal P Davé
Mar 7, 2021·Cell Chemical Biology·Anna A KudriaevaAlexey A Belogurov
Oct 29, 2020·Genome Génome / Conseil National De Recherches Canada·Rachel M PriceSheila S Teves
Jun 20, 2021·Nature Communications·Christian H GabrielAchim Kramer
Jun 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Nathan M WillyEmanuele Cocucci
Sep 30, 2021·Journal of the Royal Society, Interface·Joshua BurtonJochen Kursawe

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