| Project/Area Number |
07670549
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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 |
内科学一般
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| Research Institution | Fujita Health University |
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Principal Investigator |
OSHIMA Hisaji Fujita Health University School of Medicine, Internal Medicine, Associate Professor, 医学部, 講師 (90138008)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | glucocorticoids / receptors / steroids / therapy / transcription / 遺伝子 / 転写因子 / メッセンジャーRNA / cDNAライブラリー / レポーター遺伝子 / ゲルシフト法 |
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| Research Abstract |
Glucocorticoid hormones have been widely used as a major thearpeutic agent in various autoimmune diseases despite a wide variety of serious adverse effects. We, in this project, have identified and clarified glucocorticoid modulatory elements binding proteins (GMEB) which works as a gene specific and tissue specific modulator of regulation of gene transcription by glucocorticoids. GMEBs are now identified as a heteroologomeric complex (GMEB-1 and GMEB-2) present in cytoplasma and nucleus in cells. GMEB-1 and GMEB-2 are 68KDa and 88KDa proteins respectively. Cloning of GMEB-1 and GMEB-2 cDAA shows that these proteins have unique primary protein sequences. We find also that GMEB functions as a transcription factor where they bind to DNA as a sequence specific manner. In vitro, GMEB binds to a palindromic sequence which is most preferentialy GCGA/CNNNG/TCGC.Biological activities of GMEB can vary in different tissues and also by a change in the growth conditions of cells. In addition, GMEB activities enhanced by some chinese medicine as a tissue specific manner. These findings can be a most hopeful evidence to undrestand a gene and tissue specific modulation of the glucocorticoid hormone actions and to develop more specific and powerful glucocorticoid therapies where less adverse effects are expected.
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