The role of proteosome-mediated proteolysis in modulating potentially harmful transcription factor activity in Saccharomyces cerevisiae

Bioinformatics. 2011 Jul 1;27(13):i283-7. doi: 10.1093/bioinformatics/btr211.

Abstract

Motivation: 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.

Contact: jasmin.fisher@microsoft.com

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Fungal
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Hydrolysis
  • Proteasome Endopeptidase Complex / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stress, Physiological
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • GIS1 protein, S cerevisiae
  • Histone Demethylases
  • Proteasome Endopeptidase Complex