2000 Fiscal Year Final Research Report Summary
MOLECULAR MECHANISM OF GLUCOCORTICOID RECEPTOR REGULATION
Project/Area Number |
10470222
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Research Category |
Grant-in-Aid for Scientific Research (B).
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | The University of Tokyo (1999-2000) Asahikawa Medical College (1998) |
Principal Investigator |
TANAKA Hirotoshi The University of Tokyo Insitute of Medical Science Associate Professor, 医科学研究所, 助教授 (00171794)
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Co-Investigator(Kenkyū-buntansha) |
HANDA Hiroshi Tokyo Insitute of Technology Frontier Colaborative Res. Center Professor, フロンテイア創造共同研究センター, 教授 (80107432)
HOSONO Osamu The University of Tokyo Insitute of Medical Science Associate, 医科学研究所, 助手 (50190210)
MORIMOTO Chikao The University of Tokyo Insitute of Medical Science Professor, 医科学研究所, 教授 (30119028)
牧野 雄一 東京大学, 医科学研究所, 学術振興会特別研究員
HAYASHI Shinichi Saitama Cancer Center Research Institute Chief Investigator, 生化学部, 主任研究員 (60144862)
YUICHI Makino The University of Tokyo Insitute of Medical Science JSPS fellow (PD)
|
Project Period (FY) |
1998 – 2000
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Keywords | NUCLEAR RECEPTOR / TRANSCRIPTION FACTOR / MOLECULAR BIOLOGY / GENE EXPRESSION / PHARMACOLOGY / DRUG DEVELOPMENT / STEROID |
Research Abstract |
Glucocorticoids perform these functions by binding to a cytoplasmic receptor protein glucocorticoid receptor (GR), which is a member of the nuclear receptor superfamily and acts as a ligand-inducible transcription factor. Upon binding, GR translocates to the nucleus, whereby binds to the target DNA sequences and regulates the rate of transcription in concert with various protein factors including coactiovators, integrators, and chromatin components. We have found that this sequential process for activation of GR is modulated by cellular redox state. Moreover, we identified the regions which are apt to be mainly influenced by redox ; DNA binding domain and nuclear localization signal. We also revealed that the function of the ligand binding domain is variably modulated by ligands via interaction with distinct regions of the very domain. Further analysis, therefore, will critically demonstrate the strategy for novel drug development against GR.
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[Publications] Kiyoshi Migita,Hirotoshi Tanaka,Kensaku Okamoto,Noritada Yoshikawa,Yasufumi Ichinose,Satoshi Urayama,Satoshi Yamasaki,Hiroaki Ida,Yojiro Kawabe,Atushi Kawakami,Katsumi Eguchi: "FK506 augments glucocorticoid-mediated cyclooxygenase-2 down-regulation in human rheumatoid synovial fibroblasts"Lab.Invest.. 80(2). 135-141 (2000)
Description
「研究成果報告書概要(和文)」より
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