The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in vivo and is required for the induction of heat shock genes by oxidative stress

The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in vivo and is required for the induction of heat shock genes by oxidative stress
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DOI:
10.1091/mbc.11.7.2335
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发表时间:
2000-07-01
影响因子:
3.3
通讯作者:
Johnston, LH
Johnston, LH
中科院分区:
生物学3区
文献类型:
--
作者:
Raitt, DC;Johnson, AL;Johnston, LH

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SKN7反应调节因子在酵母的应激反应基因的诱导中发挥作用,例如,在硫氧还蛋白基因对过氧化氢的反应中。酵母热休克因子HSF1是诱导另一组应激诱导基因的核心,即热休克基因。这两个调节反式激活子,HSF1和SKN7,有某些结构上的同源性,特别是在它们的DNA结合域和卷曲结构的相邻区域的存在,这是已知的介导蛋白质-蛋白质相互作用的区域。在这里,我们提供了HSF1和SKN7在体外和体内相互作用的证据,我们发现SKN7可以与HSF1相同的调控序列结合,即热休克元件。此外,我们还证明,缺失SKN7基因并在HSF1中含有温度敏感突变的菌株对氧化应激高度敏感。我们的数据表明,SKN7和HSF1合作实现了最大限度地诱导热休克基因,以响应氧化应激。我们进一步证明,像HSF1一样,SKN7可以与自身相互作用,并且在正常生长条件下以及在氧化应激期间定位于细胞核。
The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein-protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we demonstrate that a strain deleted for the SKN7 gene and containing a temperature-sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock genes in response specifically to oxidative stress. We further show that, like Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal growth conditions as well as during oxidative stress.