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The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network

Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the...

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Autores principales: Leech, Cassandra M., Flynn, Mackenzie J., Arsenault, Heather E., Ou, Jianhong, Liu, Haibo, Zhu, Lihua Julie, Benanti, Jennifer A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209309/
https://www.ncbi.nlm.nih.gov/pubmed/32343701
http://dx.doi.org/10.1371/journal.pgen.1008600
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author Leech, Cassandra M.
Flynn, Mackenzie J.
Arsenault, Heather E.
Ou, Jianhong
Liu, Haibo
Zhu, Lihua Julie
Benanti, Jennifer A.
author_facet Leech, Cassandra M.
Flynn, Mackenzie J.
Arsenault, Heather E.
Ou, Jianhong
Liu, Haibo
Zhu, Lihua Julie
Benanti, Jennifer A.
author_sort Leech, Cassandra M.
collection PubMed
description Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 activation and the period of cell cycle arrest. Regulation of Hog1 by CN also contributes to inactivation of multiple cell cycle-regulatory transcription factors (TFs) and the decreased expression of cell cycle-regulated genes. CN-dependent downregulation of G1/S genes is dependent upon Hog1 activation, whereas CN inactivates G2/M TFs through a combination of Hog1-dependent and -independent mechanisms. These findings demonstrate that CN and Hog1 act in a coordinated manner to inhibit multiple nodes of the cell cycle-regulatory network. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors.
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spelling pubmed-72093092020-05-12 The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network Leech, Cassandra M. Flynn, Mackenzie J. Arsenault, Heather E. Ou, Jianhong Liu, Haibo Zhu, Lihua Julie Benanti, Jennifer A. PLoS Genet Research Article Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 activation and the period of cell cycle arrest. Regulation of Hog1 by CN also contributes to inactivation of multiple cell cycle-regulatory transcription factors (TFs) and the decreased expression of cell cycle-regulated genes. CN-dependent downregulation of G1/S genes is dependent upon Hog1 activation, whereas CN inactivates G2/M TFs through a combination of Hog1-dependent and -independent mechanisms. These findings demonstrate that CN and Hog1 act in a coordinated manner to inhibit multiple nodes of the cell cycle-regulatory network. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors. Public Library of Science 2020-04-28 /pmc/articles/PMC7209309/ /pubmed/32343701 http://dx.doi.org/10.1371/journal.pgen.1008600 Text en © 2020 Leech et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Leech, Cassandra M.
Flynn, Mackenzie J.
Arsenault, Heather E.
Ou, Jianhong
Liu, Haibo
Zhu, Lihua Julie
Benanti, Jennifer A.
The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network
title The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network
title_full The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network
title_fullStr The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network
title_full_unstemmed The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network
title_short The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network
title_sort coordinate actions of calcineurin and hog1 mediate the stress response through multiple nodes of the cell cycle network
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209309/
https://www.ncbi.nlm.nih.gov/pubmed/32343701
http://dx.doi.org/10.1371/journal.pgen.1008600
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