| Project/Area Number |
13470491
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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 |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
NOSE Kiyoshi SHOWA UNIV., SCH.PHARM.SCI., PROFESSOR, 薬学部, 教授 (70012747)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Kazunori SHOWA UNIV., SCH.PHARM.SCI., RESEARCH ASSOCIATE, 薬学部, 助手 (60349040)
KIM-KANEYAMA Joori SHOWA UNIV., SCH.PHARM.SCI., RESEARCH ASSOCIATE, 薬学部, 助手 (10338535)
SHIBANUMA Makoto SHOWA UNIV., SCH.PHARM.SCI., ASSOCIATE PROFESSOR, 薬学部, 助教授 (60245876)
江川 清 昭和大学, 薬学部, 講師 (00095879)
真下 順一 昭和大学, 薬学部, 講師 (60054045)
西谷 直之 昭和大学, 薬学部, 助手 (10286867)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2003: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | Hic-5 / paxillin / nuclear lozalization / c-fos / focal adhesion / 核マトリクス / 核移行 / 細胞接着斑 / パキシリン / 接着斑 / MMP / p38 / 上皮細胞 |
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| Research Abstract |
Hic-5 (hydrogen peroxide-inducible clone-5) encodes a LIM protein which localizes in the focal adhesions and participates in the signal transduction from the cell surface. The Hic-5 protein translocates from the cell surface to the nucleus under oxidative condition, and regulates several target genes such as c-fos and p21. In case of c-fos genes, the transcriptional regulatory domain located at 5'-upstream region of approximately 1.5 kb from the cap site was responsible for transactivation by Hic-5. This domain contains several cis-acting sequences, but Sp1 elements was critical for the response to Hic-5. As for the mechanism of nuclear translocation of Hic-5, the LIM domains were found to be necessary. Overexpression of a cytoplasmic factor that interacts with the LIM domain 3 of Hic-5 (PTP-PEST) decreased nuclear accumulation of Hic-5 under oxidative condition. Hic-5 has an activity to oligomerize through the LIM 4 domain, and this domain functions to direct Hic-5 to the nuclear matrix fraction. Oxidative stress increased the association of Hic-5 with the nuclear matrix. These results indicate that the focal adhesion protein Hic-5 involves in cell surface signalings as well as transcriptional regulation under oxidative conditions.
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