Involvement of non-chaperone target genes for heat shock transcription factor in cell homeostasis.
| Project/Area Number |
16K07292
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 細胞増殖 / ストレス応答 / 熱ショック転写因子 / 基本転写因子 / MAPキナーゼ経路 / プロテインホスファターゼ / 初期応答遺伝子 / 熱ショック応答 / IER2 / IER5 / IER5L / HSF1 / Protein phosphatase 2A / CDC25 / GADD45 / MAPキナーゼ / 転写開始と伸長 / タンパク分解 / 遺伝子 / 蛋白質 / ストレス |
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| Outline of Final Research Achievements |
Heat shock factor HSF1 is known as the major transcriptional regulator for chaperone genes, and it also regulates the expression of non-chaperone genes under normal growth conditions. In this study, I focused on the roles of HSF1-target genes, including immediate-early response factor IER5, general transcription factor TAF7, and cell growth regulator GADD45. IER5 functions as a modulator of protein phosphatase 2A and regulates the protein stability and activity of cell division cycle regulators. Heat-induced TAF7 is necessary for the prolonged expression of chaperone genes. GADD45 is necessary for heat stress survival. These results suggest that HSF1 is involved in the control of cell proliferation and death through regulating the expression of various non-chaperone target genes.
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| Academic Significance and Societal Importance of the Research Achievements |
HSF1は、タンパク質の恒常性維持や細胞の増殖・がん化などさまざまな生理現象に関与するが、その多くはHSPシャペロンの発現を介しての効果であると考えられている。本研究では、HSF1の多様な機能の重要性について明らかにした。得られた結果は、細胞増殖やタンパク変性ストレスに対する応答機構、および、恒常性維持機構の解明において、重要な知見を与えるものである。また、HSF1やその標的遺伝子であるIER5、およびIER2は、がん細胞で高発現しており、がん治療や予後の予測において、これらの遺伝子の役割の解明が期待される。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Heme Orientation of Cavity Mutant Hemoglobins (His F8 --> Gly) in Either alpha or beta Subunits: Circular Dichroism, (1) H NMR, and Resonance Raman Studies.2016
Author(s)
Nagai, M., Nagai, Y., Aki, Y., Sakurai, H., Mizusawa, N., Ogura, T., Kitagawa, T., Yamamoto, Y. and Nagatomo, S.
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Journal Title
Chirality
Volume: 28
Issue: 8
Pages: 585-592
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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