| Project/Area Number |
10470487
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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) |
MASHIMO Junn'ichi SHOWA UNIV.SCH.PHARM.SCI., RESEARCH ASSOCIATE, 薬学部, 助手 (60054045)
EGAWA Kiyoshi SHOWA UNIV.SCH.PHARM.SCI., LECTURER, 薬学部, 講師 (00095879)
SHIBANUMA Motoko SHOWA UNIV.SCH.PHARM.SCI., ASSOCIATE PROFESSOR, 薬学部, 助教授 (60245876)
NISHIYA Naoyuki SHOWA UNIV.SCH.PHARM.SCI., RESEARCH ASSOCIATE, 薬学部, 助手 (10286867)
大場 基 昭和大学, 薬学部, 助手 (70297018)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Hic-5 / paxillin / nuclear lozalization / c-fos / focal adhesion / 接着斑 / 過酸化水素 / 核移行 / Hic-5蛋白質 / 細胞接着斑 / 酸化ストレス |
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| Research Abstract |
Hic-5 was isolated as a hydrogen peroxide-inducible gene that encodes a focal adhesion protein with striking similarity to paxillin. Under oxidative stress to the cell, Hic-5 was found to translocate to the nuclei, whereas paxillin did not. Truncated C-terminal parts that contain LIM domains of both proteins localized to the nuclei, and N-terminal parts were suggested to be involved in cytoplasmic retention. In particular, LD4 domain of Hic-5 was the most important for cytoplasmic localization. Cytochalasin D or phorbol ester also induced nuclear localization of Hic-5. From the survey of nuclear target genes of Hic-5, expression of c-fos was found to be inclreased in Hic-5-overexpressing cells. A luciferase reporter gene that contained 5'-regions of human c-fos gene was constructed, and introduced into fibroblasts in the absence or presence of hic-5 expression vector. When nuclear localization signal was added to Hic-5, it activated the transcription of c-fos. The DNA domain that participates in the activation localized at-1.5 kb region of c-fos gene. Hic-5 was, thus, participates both in regulation of focal adhesion signalings and in transcriptional control of specific genes.
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