Centre for Integrative Bioinformatics VU, VU University Amsterdam, De Boelelaan 1081a, 1081 HV Amsterdam, The Netherlands.
Bioinformatics. 2011 Jul 1;27(13):i283-7. doi: 10.1093/bioinformatics/btr211.
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.
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.
为了维持酿酒酵母的持续生存能力，需要适当调节应对环境变化的应激反应。特别是，控制可能对细胞生长产生不利影响的蛋白质的丰度，对于从应激诱导的休眠中快速恢复至关重要。
受酵母营养饥饿反应的定性建模的启发，我们研究了营养饥饿后蛋白质降解的体内效应，结果表明，至少对于 Gis1 转录因子而言，蛋白酶体介导的控制对于快速恢复生长至关重要。其他生物信息学分析表明，潜在毒性转录调节剂的蛋白半衰期明显更短，无规卷曲区域的比例更高，且具有更多的 PEST 模体，而非危害性转录调节剂则没有这些特征。此外，抑制蛋白酶体的活性往往会增加环境应激反应过程中诱导基因的表达，超过基因组中其他基因的表达。我们的综合结果表明，蛋白酶体介导的潜在毒性转录因子的蛋白水解，在酿酒酵母中对应激反应进行了严格的调控。
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