2006 Fiscal Year Final Research Report Summary
Phosphorylation of heat shock transcription factor in the stress response
| Project/Area Number |
16570142
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SAKURAI Hiroshi Kanazawa University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00225848)
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| Project Period (FY) |
2004 – 2006
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| Keywords | stress response / heat shock transcription factor / phosphorylation / yeast |
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| Research Abstract |
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
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