| Project/Area Number |
10470222
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| 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)
|
|---|
| 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)
江口 英孝 埼玉県県立がんセンター研究所, 研究員 (00260232)
三浦 貴徳 旭川医科大学, 医学部, 助手 (90281881)
梅園 和彦 京都大学, ウィルス研究所, 教授 (50183752)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥5,100,000 (Direct Cost: ¥5,100,000)
|
|---|
| Keywords | NUCLEAR RECEPTOR / TRANSCRIPTION FACTOR / MOLECULAR BIOLOGY / GENE EXPRESSION / PHARMACOLOGY / DRUG DEVELOPMENT / STEROID / グルココルチコイド受容体 / レドックス制御 / リガンド / 薬理学 / 内分泌学 / ステロイドホルモン / 核内受容体 / 分子生物学 |
|---|
| 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.
|
