Instituto de Biología Molecular y Celular de Plantas, CSIC-Universidad Politécnica de Valencia, Ciudad Politécnica de la Innovación, Edificio 8E, Ingeniero Fausto Elio s/n, E-46022 Valencia, Spain.
Mol Microbiol. 2011 Feb;79(4):1008-23. doi: 10.1111/j.1365-2958.2010.07502.x. Epub 2010 Dec 28.
Hyperosmotic stress triggers a complex adaptive response that is dominantly regulated by the Hog1 MAP kinase in yeast. Here we characterize a novel physiological determinant of osmostress tolerance, which involves the Hog1-dependent transcriptional downregulation of ergosterol biosynthesis genes (ERG). Yeast cells considerably lower their sterol content in response to high osmolarity. The transcriptional repressors Mot3 and Rox1 are essential for this response. Both factors together with Hog1 are required to rapidly and transiently shut down transcription of ERG2 and ERG11 upon osmoshock. Mot3 abundance and its binding to the ERG2 promoter is stimulated by osmostress in a Hog1-dependent manner. As an additional layer of control, the expression of the main transcriptional activator of ERG gene expression, Ecm22, is negatively regulated by Hog1 and Mot3/Rox1 upon salt shock. Oxidative stress also triggers repression of ERG2, 11 transcription and a profound decrease in total sterol levels. However, this response was only partially dependent on Mot3/Rox1 and Hog1. Finally, we show that the upc2-1 mutation confers stress insensitive hyperaccumulation of ergosterol, overexpression of ERG2, 11 and severe sensitivity to salt and oxidative stress. Our results indicate that transcriptional control of ergosterol biosynthesis is an important physiological target of stress signalling.
高渗胁迫引发一种复杂的适应性反应，这种反应主要受酵母中 Hog1 MAP 激酶调控。在这里，我们描述了一种新的耐渗透压胁迫的生理决定因素，该因素涉及到 Hog1 依赖性的麦角固醇生物合成基因（ERG）转录下调。酵母细胞在高渗透压条件下会显著降低固醇含量。转录抑制因子 Mot3 和 Rox1 是该反应所必需的。这两个因子与 Hog1 一起，在渗透压冲击时迅速和短暂地关闭 ERG2 和 ERG11 的转录。Mot3 的丰度及其与 ERG2 启动子的结合，受 Hog1 依赖的方式刺激。作为额外的控制层，ERG 基因表达的主要转录激活因子 Ecm22 的表达受 Hog1 和 Mot3/Rox1 在盐冲击时的负调控。氧化应激也会触发 ERG2、11 转录的抑制和总固醇水平的显著下降。然而，这种反应仅部分依赖于 Mot3/Rox1 和 Hog1。最后，我们发现 upc2-1 突变赋予酵母耐渗透压胁迫的麦角固醇超积累、ERG2、11 的过表达以及对盐和氧化胁迫的高度敏感性。我们的结果表明，麦角固醇生物合成的转录控制是应激信号的一个重要生理靶点。
