| Project/Area Number |
11470488
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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 |
SHIBANUMA Motoko SHOWA UNIV. SCH. PHARM. SCI., ASSOCIATE PROFESSOR, 薬学部, 助教授 (60245876)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIYA Naoyuki SHOWA UNIV. SCH. PHARM. SCI., RESEARCH ASSOCIATE, 薬学部, 助手 (10286867)
MASHIMO Junnichi SHOWA UNIV. SCH. PHARM. SCI., Lecturer, 薬学部, 講師 (60054045)
EGAWA Kiyoshi SHOWA UNIV. SCH. PHARM. SCI., Lecturer, 薬学部, 講師 (00095879)
大場 基 昭和大学, 薬学部, 助手 (70297018)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | Hic-5 / paxillin / focal adhesion / c-fos / oxidative stress / Smad3 / NES / 過酸化水素 / c-foc |
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| Research Abstract |
Hic-5 is a component of the focal adhesion complex, and is involved in regulation of signaling elicited from integrins. In fibroblastic cells, Hie5 was found to compete focal adhesion kinase (FAK) with paxillin, thereby inhibited cell spreading and motility. This inhibition was restored yb overexpression of v-Src or constitutive active form of Raci. These results indicate that Hie5 blocks integrin signals at the focal adhesion and regulates downstream signaling pathways. On the other hand, Hic-5 translocated to the nucleus under oxidative stress. Hic-5 contains nuclear exclusion signal in its N-terminal LD3 domain, and redox-sensitive cystein residues that participate in the nuclear translocation. In the nucleus, Hic-5 seemed to regulate transcription of several target genes such as c-fos and p21.In reporter assays, Hic-5 stimulated c-los enhancer through activation of Sp1 elements. Direct association between Hic-5 and Spi was not detected, but Hic-5 formed a complex with Smad3 that is involved in TGF*-signalin. Thus, Hic-5 participates not only in the surface signaling, but also in the nuclear transcriptional regulation.
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