Phosphorylation of heat shock transcription factor in the stress response

应激反应中热休克转录因子的磷酸化

基本信息

批准号：
16570142
负责人：
SAKURAI Hiroshi
金额：
$ 2.3万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16570142/
关键词：
stress response heat shock transcription factor phosphorylation yeast

项目摘要

All organisms respond to elevated temperatures by changing transcription programs and expressing a set of proteins called heat shock proteins (HSPs). In eukaryotes, heat sock transcription factor (HSF) activates transcription of HSP genes. The target genes of HSF contain a cis-acting sequence designated the heat shock element. The baker's yeast, Saccharomyces cerevisiae, has one HSF encoded by the HSF1 locus. Under heat shock condition, Hsfl protein is extensively phosphorylated and acquires a stronger activating ability, although detailed regulatory mechanisms remain unknown. In this project, I focused on mechanisms of Hsfl phosphorylation and dephosphorylation' and 'roles of Hsfl in the response to various stresses'.By using DNA microarray analysis, we have shown that yeast Hsfl is necessary for heat-induced transcription of〜70 genes and that target genes encode molecular chaperones and proteins involved in a broad range biological functions. We have characterized multicopy suppressor genes of a temperature-sensitive hsfl mutation and found that Hsfl in concert with a protein kinase Pkc1 regulates cell wall remodeling in response to heat shock. Heat-induced hyperphosphorylation of Hsfl was required for transcriptional activation of approximately half of Hsfl target genes. This requirement was related to cooperative interactions among Hsfl trimers bound to the HSE. Consistent with this, oligomerization of Hsfl was prerequisite for stress-induced hyperphosphorylation of Hsfl. We have also shown that human HSF1 recognizes HSEs in a slightly different way than yeast Hsfl.Taken together, these results suggest that the architecture of the HSE is an important determinant for HSF-HSE interactions

所有生物体通过改变转录程序并表达一组称为热休克蛋白（HSP）的蛋白质来应对升高的温度。在真核生物中，热袜转录因子（HSF）激活了HSP基因的转录。 HSF的靶基因包含一个指定热冲击元件的顺式作用序列。面包师的酵母，酿酒酵母的葡萄糖，有一个由HSF1基因座编码的HSF。在热休克条件下，HSFL蛋白被广泛磷酸化并获得更强的激活能力，尽管详细的调节机制仍然未知。在这个项目中，我专注于HSFL磷酸化和去磷酸化的机制，而HSFL在对各种压力的响应中的作用”。通过使用DNA微阵列分析，我们表明酵母HSFL对于〜70个基因的热诱导转录是〜70个基因的转录，以及该靶基因构成基因的生物范围涉及的范围广泛。我们表征了温度敏感的HSFL突变的多拷贝抑制基因，发现HSFL与蛋白激酶PKC1一致，可调节对热休克的响应细胞壁重塑。热诱导的HSFL热磷酸化是需要大约一半HSFL靶基因的转录激活的。该要求与与HSE结合的HSFL三聚体之间的合作相互作用有关。与此相一致，HSFL的寡聚是应力诱导的HSFL过度磷酸化的先决条件。我们还表明，人类HSF1以与酵母HSFL略有不同的方式识别HSE。同时，这些结果表明HSE的体系结构是HSF-HSE相互作用的重要决定因素