| Project/Area Number |
13480231
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | YAMAGUCHI UNIVERSITY |
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Principal Investigator |
NAKAI Akira Yamaguchi University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (60252516)
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| Co-Investigator(Kenkyū-buntansha) |
INOUYE Sachie Yamaguchi University, graduate School of Medicine, Lecture, 大学院・医学研究科, 講師 (60159978)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2002: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2001: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | cell cycle / heat shock protein / transcription factor / lens / testis / apoptosis / stress / mouse / 熱ショック / 精子 / シャペロン / 腎臓 / 熱ショック応答 / 熱ショック転写因子 |
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| Research Abstract |
It is well known that cells can survive against an exposure to lethal temperatures when cells are pre-incubated at sublethal high temperatures. This phenomenon is called "induced thermotolerance", and is regulated by heat shock transcription factors (HSFs). In this research project, we uncovered novel two mechanisms of cell protection controlled by HSF1. First, HSF1 and HSF3 in chicken B lymphocytes up-regulate Hsp90α expression in normally growing cells. Furthermore, Hsp90 stabilizes Cdc2 protein that is essential for G_2 to M phase transition. Second, HSF1 is protecting cell death against various kinds of stresses independently of the activation of heat shock genes. HSF1 may regulate unknown target genes other than heat shock genes.
To understand physiological roles of HSFs, we analyzed mice mutated in HSF4 and HSF1. We found that HSF4 is essential for lens development. The lack of HSF4 expression in the lens results in progression of cataract. It was also reported from other group that mutation of HSF4 gene is associated with hereditary cataract. We also found that HSF1 promotes apoptosis of male germ cells exposed to thermal stress. HSF1 activates a novel heat shock gene T-cell death-associated gene 51 (TDAG51) that is a pro-apoptotic gene, and is essential for Fas expression in T cell hybridoma. The induction of TDAG51 as well as Fas in response to heat shock was lacking in the testis in HSF1-null mice. Thus, we identified a novel HSF1-mediated quality control mechanism in spermatogenesis.
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