Journal article
Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
Molecular systems biology, Vol.10(11), pp.759-n/a
11/19/2014
DOI: 10.15252/msb.20145120
PMCID: PMC4299600
PMID: 25411400
Abstract
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.
Details
- Title: Subtitle
- Pathway connectivity and signaling coordination in the yeast stress-activated signaling network
- Creators
- Deborah Chasman - Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI, USAYi-Hsuan Ho - Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USADavid B Berry - Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USACorey M Nemec - Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USAMatthew E MacGilvray - Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USAJames Hose - Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USAAnna E Merrill - Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USAM Violet Lee - Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USAJessica L Will - Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USAJoshua J Coon - Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI, USA Department of Biological Chemistry, University of Wisconsin-Madison, Madison, WI, USAAseem Z Ansari - Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI, USA ansari@biochem.wisc.edu craven@biostat.wisc.edu agasch@wisc.eduMark Craven - Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI, USA Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI, USA Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA ansari@biochem.wisc.edu craven@biostat.wisc.edu agasch@wisc.eduAudrey P Gasch - Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI, USA ansari@biochem.wisc.edu craven@biostat.wisc.edu agasch@wisc.edu
- Resource Type
- Journal article
- Publication Details
- Molecular systems biology, Vol.10(11), pp.759-n/a
- DOI
- 10.15252/msb.20145120
- PMID
- 25411400
- PMCID
- PMC4299600
- NLM abbreviation
- Mol Syst Biol
- ISSN
- 1744-4292
- eISSN
- 1744-4292
- Publisher
- England
- Grant note
- T32HG002760 / NHGRI NIH HHS R01 GM083989 / NIGMS NIH HHS T32 HG002760 / NHGRI NIH HHS T32 GM008505 / NIGMS NIH HHS T15 LM007359 / NLM NIH HHS UL1 TR000427 / NCATS NIH HHS R01 GM080148 / NIGMS NIH HHS 5T15LM007359 / NLM NIH HHS UL1 RR025011 / NCRR NIH HHS T32 GM007133 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/19/2014
- Academic Unit
- Pathology; Injury Prevention Research Center
- Record Identifier
- 9984047605402771
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