2001 Fiscal Year Final Research Report Summary
Regulation of adhesion signals by a focal adhesion protein, Hie5.
| 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)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Hic-5 / paxillin / focal adhesion / c-fos / oxidative stress / Smad3 |
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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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Research Products
(16 results)
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[Publications] Jia, Y., Ramsom, R, F., Shibanuma, M., Liu, C., Welsh, M, J., and Smoyer, W, E.: "Identification and characterization of hic-5/ARA55 as an hsp27 binding protein"J. Biol. Chem. 276. 39911-39918 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ueno, M., Sonoda, Y., Funakoshi, M., Mukaida, N., Nose, K., and Kasahara, T.: "Differential induction of JE/MCP-1 in subclones from a murine macrophage cell line, RAW 264.7 : Role of kB-3 binding protein"Cytokine. 12. 207-219 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Egawa, K., Yamori, T., Nosaka, C., Kunimoto, S., Takeuchi, T., and Nose, K: "Deoxynubomycin is a selective ant-tumor agent inducing apoptosis and inhibiting topoisomerase I"Biol. Pharm. Bullet. 23. 1036-1040 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Ishino, K., Kaneyama, S., Shibanuma, M., and Nose, K: "Specific decrease in the level of Hic-5, a focal adhesion protein, during immortalization of mouse embryonic fibroblasts, and its association with focal adhesion kinase"J. Cell. Biochem. 76. 411-419 (2000)
Description
「研究成果報告書概要(欧文)」より
