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

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 halflife,
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.