title: Fine-tuning of the Msn2/4-mediated yeast stress responses as revealed by systematic deletion of Msn2/4 partners.
abstract: The Msn2 and Msn4 transcription factors play major roles in the yeast general stress response by mediating the transcription of hundreds of genes. Despite extensive information on Msn2/4-mediated gene expression profiles, much less is known regarding the network of proteins that regulate its activity. Here we describe a systematic approach designed to examine the roles of 35 Msn2/4 partners in regulating Msn2/4 transcriptional activity in the face of four different environmental conditions. Our analysis indicates that single deletions of 26 Msn2/4 partners significantly affect Msn2/4 transcription activity under four different conditions. The low functional redundancy of the Msn2 regulatory network indicates that Msn2/4 activity is finely tuned by many of Msn2/4 partners to provide an optimized stress response through differential activation, nuclear localization, degradation, and chromatin remodeling. Our specific analysis of Msn2 activity showed that a relatively large number of partners act to suppress Msn2 activity under nonstress conditions through independent mechanisms, including cytoplasmic retention, proteosome-mediated Msn2 degradation, and chromatin remodeling. Such negative regulation is crucial to minimize the cost of uncontrolled stress response gene expression and ensures a high growth rate in the absence of stress.
authors.affiliation: Departments of Life Science, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Sadeh
authors.forename: Natalia
authors.initials: N
authors.lastname: Movshovich
authors.forename: Misha
authors.initials: M
authors.lastname: Volokh
authors.forename: Larisa
authors.initials: L
authors.lastname: Gheber
authors.forename: Amir
authors.initials: A
authors.lastname: Aharoni
mesh_terms: D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D005964:Glucosyltransferases / Q000096:biosynthesis / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D050296:Microbial Viability; D018832:Molecular Chaperones / Q000235:genetics; D009535:Nicotinamidase / Q000096:biosynthesis / Q000235:genetics; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C112591:HSP12 protein, S cerevisiae; D006360:Heat-Shock Proteins; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C470937:Whi2 protein, S cerevisiae; C110856:proteasome maturation protein; D049452:Green Fluorescent Proteins; D005964:Glucosyltransferases; C099692:trehalose synthase; D017868:Cyclic AMP-Dependent Protein Kinases; D009535:Nicotinamidase; C474330:PNC1 protein, S cerevisiae