权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

所有生物体都通过改变转录程序和表达一组称为热休克蛋白（HSPs）的蛋白质来应对高温。在真核生物中，热袜子转录因子（HSF）激活热袜子基因的转录。HSF靶基因包含一个顺式作用序列，称为热休克元件。面包酵母（Saccharomyces cerevisiae）有一个HSF1位点编码的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，但详细的调控机制尚不清楚。在这个项目中，我重点研究了Hsfl磷酸化和去磷酸化的机制以及Hsfl在各种应激反应中的作用。通过DNA微阵列分析，我们发现酵母Hsfl是热诱导转录约70个基因所必需的，靶基因编码参与广泛生物学功能的分子伴侣和蛋白质。我们已经鉴定了温度敏感hsfl突变的多拷贝抑制基因，并发现hsfl与蛋白激酶Pkc1一起调节细胞壁重塑以响应热休克。大约一半Hsfl靶基因的转录激活需要热诱导Hsfl的过度磷酸化。这一要求与与HSE结合的Hsfl三聚体之间的协同相互作用有关。与此一致的是，Hsfl的寡聚化是应激诱导Hsfl过度磷酸化的先决条件。我们还表明，人类HSF1与酵母Hsfl识别hsse的方式略有不同。综上所述，这些结果表明HSE的结构是HSF-HSE相互作用的重要决定因素