title: Condition-specific genetic interaction maps reveal crosstalk between the cAMP/PKA and the HOG MAPK pathways in the activation of the general stress response.
abstract: Cells must quickly respond and efficiently adapt to environmental changes. The yeast Saccharomyces cerevisiae has multiple pathways that respond to specific environmental insults, as well as a generic stress response program. The later is regulated by two transcription factors, Msn2 and Msn4, that integrate information from upstream pathways to produce fast, tunable, and robust response to different environmental changes. To understand this integration, we employed a systematic approach to genetically dissect the contribution of various cellular pathways to Msn2/4 regulation under a range of stress and growth conditions. We established a high-throughput liquid handling and automated flow cytometry system and measured GFP levels in 68 single-knockout and 1,566 double-knockout strains that carry an HSP12-GFP allele as a reporter for Msn2/4 activity. Based on the expression of this Msn2/4 reporter in five different conditions, we identified numerous genetic and epistatic interactions between different components in the network upstream to Msn2/4. Our analysis gains new insights into the functional specialization of the RAS paralogs in the repression of stress response and identifies a three-way crosstalk between the Mediator complex, the HOG MAPK pathway, and the cAMP/PKA pathway.
authors.affiliation: School of Computer Science & Engineering Institute of Life Sciences Hebrew University, Jerusalem, Israel.
authors.forename: Jenia
authors.initials: J
authors.lastname: Gutin
authors.affiliation: School of Computer Science & Engineering Institute of Life Sciences Hebrew University, Jerusalem, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Sadeh
authors.affiliation: School of Computer Science & Engineering Institute of Life Sciences Hebrew University, Jerusalem, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Rahat
authors.affiliation: Department of Life Science, National Institute for Biotechnology in the Negev Ben-Gurion University of the Negev, Be'er Sheva, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Aharoni
authors.affiliation: School of Computer Science & Engineering Institute of Life Sciences Hebrew University, Jerusalem, Israel nir@cs.huji.ac.il.
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D015003:Yeasts / Q000201:enzymology / Q000378:metabolism
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Msn2 and Msn4; budding yeast; genetic interactions; signaling pathways; transcriptional response to stress