title: Pathway connectivity and signaling coordination in the yeast stress-activated signaling network.
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.
authors.affiliation: Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Chasman
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Ho
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Berry
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Corey M
authors.initials: CM
authors.lastname: Nemec
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: MacGilvray
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hose
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Merrill
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: M Violet
authors.initials: MV
authors.lastname: Lee
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Will
authors.affiliation: 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, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Coon
authors.affiliation: 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.edu.
authors.forename: Aseem Z
authors.initials: AZ
authors.lastname: Ansari
authors.affiliation: 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.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Craven
authors.affiliation: 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.
authors.forename: Audrey P
authors.initials: AP
authors.lastname: Gasch
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D056084:Genetic Fitness; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012965:Sodium Chloride / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D012965:Sodium Chloride; D012319:RNA Polymerase II; D017027:Protein Tyrosine Phosphatases
keywords: environmental stress; integer programming; proteomics; signal transduction; transcriptomics