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Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence
Cells arrest growth and enter a quiescent state upon nutrient deprivation. However, the molecular processes by which cells respond to different starvation signals to regulate exit from the cell division cycle and initiation of quiescence remains poorly understood. To study the role of protein expres...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418281/ https://www.ncbi.nlm.nih.gov/pubmed/37577636 http://dx.doi.org/10.1101/2023.08.03.551843 |
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author | Sun, Siyu Tranchina, Daniel Gresham, David |
author_facet | Sun, Siyu Tranchina, Daniel Gresham, David |
author_sort | Sun, Siyu |
collection | PubMed |
description | Cells arrest growth and enter a quiescent state upon nutrient deprivation. However, the molecular processes by which cells respond to different starvation signals to regulate exit from the cell division cycle and initiation of quiescence remains poorly understood. To study the role of protein expression and signaling in quiescence we combined temporal profiling of the proteome and phosphoproteome using stable isotope labeling with amino acids in cell culture (SILAC) in Saccharomyces cerevisiae (budding yeast). We find that carbon and phosphorus starvation signals activate quiescence through largely distinct remodeling of the proteome and phosphoproteome. However, increased expression of mitochondrial proteins is associated with quiescence establishment in response to both starvation signals. Deletion of the putative quiescence regulator RIM15, which encodes a serine-threonine kinase, results in reduced survival of cells starved for phosphorus and nitrogen, but not carbon. However, we identified common protein phosphorylation roles for RIM15 in quiescence that are enriched for RNA metabolism and translation. We also find evidence for RIM15-mediated phosphorylation of some targets, including IGO1, prior to starvation consistent with a functional role for RIM15 in proliferative cells. Finally, our results reveal widespread catabolism of amino acids in response to nitrogen starvation, indicating widespread amino acid recycling via salvage pathways in conditions lacking environmental nitrogen. Our study defines an expanded quiescent proteome and phosphoproteome in yeast, and highlights the multiple coordinated molecular processes at the level of protein expression and phosphorylation that are required for quiescence. |
format | Online Article Text |
id | pubmed-10418281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-104182812023-08-12 Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence Sun, Siyu Tranchina, Daniel Gresham, David bioRxiv Article Cells arrest growth and enter a quiescent state upon nutrient deprivation. However, the molecular processes by which cells respond to different starvation signals to regulate exit from the cell division cycle and initiation of quiescence remains poorly understood. To study the role of protein expression and signaling in quiescence we combined temporal profiling of the proteome and phosphoproteome using stable isotope labeling with amino acids in cell culture (SILAC) in Saccharomyces cerevisiae (budding yeast). We find that carbon and phosphorus starvation signals activate quiescence through largely distinct remodeling of the proteome and phosphoproteome. However, increased expression of mitochondrial proteins is associated with quiescence establishment in response to both starvation signals. Deletion of the putative quiescence regulator RIM15, which encodes a serine-threonine kinase, results in reduced survival of cells starved for phosphorus and nitrogen, but not carbon. However, we identified common protein phosphorylation roles for RIM15 in quiescence that are enriched for RNA metabolism and translation. We also find evidence for RIM15-mediated phosphorylation of some targets, including IGO1, prior to starvation consistent with a functional role for RIM15 in proliferative cells. Finally, our results reveal widespread catabolism of amino acids in response to nitrogen starvation, indicating widespread amino acid recycling via salvage pathways in conditions lacking environmental nitrogen. Our study defines an expanded quiescent proteome and phosphoproteome in yeast, and highlights the multiple coordinated molecular processes at the level of protein expression and phosphorylation that are required for quiescence. Cold Spring Harbor Laboratory 2023-08-04 /pmc/articles/PMC10418281/ /pubmed/37577636 http://dx.doi.org/10.1101/2023.08.03.551843 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Sun, Siyu Tranchina, Daniel Gresham, David Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence |
title | Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence |
title_full | Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence |
title_fullStr | Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence |
title_full_unstemmed | Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence |
title_short | Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence |
title_sort | parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418281/ https://www.ncbi.nlm.nih.gov/pubmed/37577636 http://dx.doi.org/10.1101/2023.08.03.551843 |
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