| Project/Area Number |
13470215
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TANAKA Hirotoshi The University of Tokyo, Institute 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 Institute of Technology, Frontier Collaborative Research Center, Professor, フロンティア創造研究センター, 教授 (80107432)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | GENE / TRANSCRIPTION / NUCLEIC ACID / PHYSIOLOGY / PATHOLOGY / ENDOCRINOLOGY / PHARMACOLOGY / MOLECULAR BIOLOGY / ステロイドホルモン / 転写因子 / 共役因子 / DNA / RNA / グルココルチコイド / 発生工学 / 核内レセプター / 転写調節 |
|---|
| Research Abstract |
Nuclear receptors are a ligand-inducible transcription factor and regulate variety of physiological functions. Among others, the glucocorticoid receptor (GR) is a receptor for adrenocorticoglucocorticoid and pharmaceutical glucocorticoids. We have shown that GR function is modulated by a number of cellular factors including redox state, hsp90, and a novel nuclear protein HEXIM1. Moreover, a novel class of synthetic glucocorticoid cortivazol elicited differential modulation of AF-1 function of the GR. This ligand-dependent modulation of AF-1 is shown to involve helix 3 and 5 of the ligand binding domain of the GR and a p160 coactivator TIF2. Concerning the biological role of HEXIM1, we performed microarray analysis for glucocorticoiid-regulated gene expression, and showed that HEXIM1 desensitizes cells to glucocorticoids via sequestration of the GR into a particular subdomain of the nucleus.
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