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2000 Fiscal Year Final Research Report Summary

ANALYSIS OF CYTOPLASMIC FACTORS THAT PARTICIPATE IN GROWTH ARREST INDUCED BY OXIDATIVE STRESS

Research Project

Project/Area Number 10470487
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionSHOWA UNIVERSITY

Principal Investigator

NOSE Kiyoshi  SHOWA UNIV.SCH.PHARM.SCI., PROFESSOR, 薬学部, 教授 (70012747)

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)
Project Period (FY) 1998 – 2000
KeywordsHic-5 / paxillin / nuclear lozalization / c-fos / focal adhesion / 接着斑
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.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Nishiya,N. et al: "The LIM domains of hic-5 protein recognize specific DNA fragments"Nuci.Acids Res. 26. 4267-4273 (1998)

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  • [Publications] Fujita,H., et al.: "Interaction of Hic-5 with a focal adhesion tinase"J.Biol.Chem.. 273. 26516-26521 (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] Nishiya,N., et al.: "Hic-5 binds to the protein tyrosine phosphatase PEST."J.Biol.Chem.. 274. 9847-9853 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kim-Kaneyama,J., et al.: "Significance of nuclear relocalization of ERK1/2"J.Biol.Chem.. 275. 20685-20692 (2000)

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  • [Publications] Nishiya, N., Tachibana, K., Shibanuma, M., Mashimo, J., and Nose, K.: "Hic-5 reduced cell spreading on fibronectin : Competitive effects between paxillin and Hic-5 through interaction with FAK."Mol.Cell.Biol.. (in press).

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kim-Kaneyama, J., Nose, K., and Shibanuma, M.: "Significance of nuclear relocalization or ERK1/2 in reactivation of c-fos transcription and DNA synthesis in senescent fibroblasts."J.Biol.Chem.. 275. 20685-20692 (2000)

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  • [Publications] Mashimo, J., Shibanuma, M., Satoh, H., Chida, K., and Nose, K.: "Genomic structure and chromosomal mapping of the mouse hic-5 gene that encodes a focal adhesion protein."Gene. 249. 99-103 (2000)

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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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  • [Publications] Egawa, K., and Nose, K.: "Involvement of stress-activated kinase p38 in p53-independent induction of p21/WAF1/Cip1 gene expression."J.Health Sci.. 46. 200-203 (2000)

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  • [Publications] Egawa, K., Yamori, T., Nosaka, C., Kunimoto, S., Takeuchi, T., and Nose, K.: "Deoxynubomycin is a selective anti-tumor agent inducing apoptosis and inhibiting topoisomerase I."Biol.Pharm.Bullet.. 23. 1036-1040 (2000)

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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)

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Published: 2002-03-26  

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