Proteome Birthdating Reveals Age-Selectivity of Protein Ubiquitination.

Autor:	Meadow ME; Department of Biology, University of Rochester, New York, USA; Medical Scientist Training Program, University of Rochester, New York, USA., Broas S; Department of Biology, University of Rochester, New York, USA., Hoare M; Department of Biology, University of Rochester, New York, USA., Alimohammadi F; Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York, USA., Welle KA; University of Rochester Mass Spectrometry Resource Laboratory, New York, USA., Swovick K; University of Rochester Mass Spectrometry Resource Laboratory, New York, USA., Hryhorenko JR; University of Rochester Mass Spectrometry Resource Laboratory, New York, USA., Martinez JC; Department of Biology, University of Rochester, New York, USA., Biashad SA; Department of Biology, University of Rochester, New York, USA., Seluanov A; Department of Biology, University of Rochester, New York, USA; Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA., Gorbunova V; Department of Biology, University of Rochester, New York, USA; Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA., Buchwalter A; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA., Ghaemmaghami S; Department of Biology, University of Rochester, New York, USA; University of Rochester Mass Spectrometry Resource Laboratory, New York, USA. Electronic address: sina.ghaemmaghami@rochester.edu.
Jazyk:	angličtina
Zdroj:	Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2024 Jul; Vol. 23 (7), pp. 100791. Date of Electronic Publication: 2024 May 24.
DOI:	10.1016/j.mcpro.2024.100791
Abstrakt:	Within a cell, proteins have distinct and highly variable half-lives. As a result, the molecular ages of proteins can range from seconds to years. How the age of a protein influences its environmental interactions is a largely unexplored area of biology. To investigate the age-selectivity of cellular pathways, we developed a methodology termed "proteome birthdating" that barcodes proteins based on their time of synthesis. We demonstrate that this approach provides accurate measurements of protein turnover kinetics from a single biological sample encoding multiple labeling time-points. As a first application of the birthdated proteome, we investigated the age distribution of the human ubiquitinome. Our results indicate that the vast majority of ubiquitinated proteins in a cell consist of newly synthesized proteins and that these young proteins constitute the bulk of the degradative flux through the proteasome. Rapidly ubiquitinated nascent proteins are enriched in cytosolic subunits of large protein complexes. Conversely, proteins destined for the secretory pathway and vesicular transport have older ubiquitinated populations. Our data also identify a smaller subset of older ubiquitinated cellular proteins that do not appear to be targeted to the proteasome for rapid degradation. Together, our data provide an age census of the human ubiquitinome and establish proteome birthdating as a robust methodology for investigating the protein age-selectivity of diverse cellular pathways. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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