Elucidation of the Intracellular Signaling Networks Involved in the Proliferation and Functional Differentiation Induced by Cell-cell Contact in Vascular Endothelial Cells.
| Project/Area Number |
16590695
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
HIRANO Mayumi Kyushu University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究院, 助手 (80336031)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Katsuya Kyushu University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究院, 講師 (80291516)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Vascular endothelial cells / cell-cell contact / p27^<Kip1> / promoter region / small G protein / Rac1 / transcription activity / growth arrest |
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| Research Abstract |
The present study demonstrated for the first time that the activation of Rac1 due to the formation of the cell-cell contact plays a critical role in the transcriptional up-regulation of p27^<Kip1>, thereby facilitating the contact-induced growth arrest in vascular endothelial cells. The induction of the homophilic cell-cell contact by adding the extra numbers of endothelial cells facilitated the cell cycle arrest, activated Rac1 but not RhoA, and up-regulated p27^<Kip1> mRNA. Such up-regulation of p27^<Kip1> mRNA was abolished by introducing the Rac1 inhibitor protein conjugated with the cell-penetrating peptide of human immunodeficiency viral Tat protein. Rac1 was thus suggested to mediate the contact-induced transcriptional up-regulation of p27^<Kip1>. We thus isolated the full-length of the porcine p27^<Kip1> gene, and examined the role of Rac1 in the contact-induced activation of the p27^<Kip1> promoter, using a luciferase reporter assay. The promoter activity was activated by adding the extra number of endothelial cells but not HeLa cells. Transduction of the Rac1 inhibitory protein significantly inhibited the promoter activation induced by the formation of the cell-cell contact. Analyzing various regions identified region -620〜-573 from the initiation codon to be responsible for the contact-induced, Rac1-dependent activation of the p27^<Kip1> promoter. Our findings thus proposes a novel mechanism of the transcriptional regulation of p27^<Kip1>, which is responsible for the contact-induced growth arrest in vascular endothelial cells.
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Report
(3 results)
Research Products
(26 results)
