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Pathway connectivity and signaling coordination in the yeast stress-activated signaling network

Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate availa...

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Autores principales: Chasman, Deborah, Ho, Yi-Hsuan, Berry, David B, Nemec, Corey M, MacGilvray, Matthew E, Hose, James, Merrill, Anna E, Lee, M Violet, Will, Jessica L, Coon, Joshua J, Ansari, Aseem Z, Craven, Mark, Gasch, Audrey P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299600/
https://www.ncbi.nlm.nih.gov/pubmed/25411400
http://dx.doi.org/10.15252/msb.20145120
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author Chasman, Deborah
Ho, Yi-Hsuan
Berry, David B
Nemec, Corey M
MacGilvray, Matthew E
Hose, James
Merrill, Anna E
Lee, M Violet
Will, Jessica L
Coon, Joshua J
Ansari, Aseem Z
Craven, Mark
Gasch, Audrey P
author_facet Chasman, Deborah
Ho, Yi-Hsuan
Berry, David B
Nemec, Corey M
MacGilvray, Matthew E
Hose, James
Merrill, Anna E
Lee, M Violet
Will, Jessica L
Coon, Joshua J
Ansari, Aseem Z
Craven, Mark
Gasch, Audrey P
author_sort Chasman, Deborah
collection PubMed
description Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown ‘hubs’ of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology.
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spelling pubmed-42996002015-01-20 Pathway connectivity and signaling coordination in the yeast stress-activated signaling network Chasman, Deborah Ho, Yi-Hsuan Berry, David B Nemec, Corey M MacGilvray, Matthew E Hose, James Merrill, Anna E Lee, M Violet Will, Jessica L Coon, Joshua J Ansari, Aseem Z Craven, Mark Gasch, Audrey P Mol Syst Biol Articles Stressed cells coordinate a multi-faceted response spanning many levels of physiology. Yet knowledge of the complete stress-activated regulatory network as well as design principles for signal integration remains incomplete. We developed an experimental and computational approach to integrate available protein interaction data with gene fitness contributions, mutant transcriptome profiles, and phospho-proteome changes in cells responding to salt stress, to infer the salt-responsive signaling network in yeast. The inferred subnetwork presented many novel predictions by implicating new regulators, uncovering unrecognized crosstalk between known pathways, and pointing to previously unknown ‘hubs’ of signal integration. We exploited these predictions to show that Cdc14 phosphatase is a central hub in the network and that modification of RNA polymerase II coordinates induction of stress-defense genes with reduction of growth-related transcripts. We find that the orthologous human network is enriched for cancer-causing genes, underscoring the importance of the subnetwork's predictions in understanding stress biology. Blackwell Publishing Ltd 2014-11-19 /pmc/articles/PMC4299600/ /pubmed/25411400 http://dx.doi.org/10.15252/msb.20145120 Text en © 2014 The Authors. Published under the terms of the CC BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Chasman, Deborah
Ho, Yi-Hsuan
Berry, David B
Nemec, Corey M
MacGilvray, Matthew E
Hose, James
Merrill, Anna E
Lee, M Violet
Will, Jessica L
Coon, Joshua J
Ansari, Aseem Z
Craven, Mark
Gasch, Audrey P
Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
title Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
title_full Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
title_fullStr Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
title_full_unstemmed Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
title_short Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
title_sort pathway connectivity and signaling coordination in the yeast stress-activated signaling network
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299600/
https://www.ncbi.nlm.nih.gov/pubmed/25411400
http://dx.doi.org/10.15252/msb.20145120
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