title: The role of proteosome-mediated proteolysis in modulating potentially harmful transcription factor activity in Saccharomyces cerevisiae.
abstract: BACKGROUND
  The appropriate modulation of the stress response to variable environmental conditions is necessary to maintain sustained viability in Saccharomyces cerevisiae. Particularly, controlling the abundance of proteins that may have detrimental effects on cell growth is crucial for rapid recovery from stress-induced quiescence.
  
  
  RESULTS
  Prompted by qualitative modeling of the nutrient starvation response in yeast, we investigated in vivo the effect of proteolysis after nutrient starvation showing that, for the Gis1 transcription factor at least, proteasome-mediated control is crucial for a rapid return to growth. Additional bioinformatics analyses show that potentially toxic transcriptional regulators have a significantly lower protein half-life, a higher fraction of unstructured regions and more potential PEST motifs than the non-detrimental ones. Furthermore, inhibiting proteasome activity tends to increase the expression of genes induced during the Environmental Stress Response more than those in the rest of the genome. Our combined results suggest that proteasome-mediated proteolysis of potentially toxic transcription factors tightly modulates the stress response in yeast.
  
  
  BACKGROUND
  jasmin.fisher@microsoft.com
authors.affiliation: Centre for Integrative Bioinformatics VU, VU University Amsterdam, De Boelelaan 1081a, 1081 HV Amsterdam, The Netherlands.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bonzanni
authors.forename: Nianshu
authors.initials: N
authors.lastname: Zhang
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oliver
authors.forename: Jasmin
authors.initials: J
authors.lastname: Fisher
mesh_terms: D015966:Gene Expression Regulation, Fungal; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C400297:GIS1 protein, S cerevisiae; D056466:Histone Demethylases; D046988:Proteasome Endopeptidase Complex