| Project/Area Number |
15590972
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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 |
Endocrinology
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| Research Institution | Shinshu University |
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Principal Investigator |
MIYAMOTO Takahide Shinshu University Graduate School, Department of Aging Medicine and Geriatrics, Assistant Professor, 医学研究科, 講師 (20192768)
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| Co-Investigator(Kenkyū-buntansha) |
KOMATSU Mitsuhisa Shinshu University Graduate School, Department of Aging Medicine and Geriatrics, Assistant Professor, 医学部附属病院, 講師 (90221978)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | nuclear receptor / transcriptional mediator / phage display system / PPAR / vitamin D3 / T7ファージディスプレイ / 共役因子 / VDR / クロストーク / 転写因子 / 相互作用 / リガンド / クローニング |
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| Research Abstract |
Nuclear hormone receptors for steroids, retinoids, thyroid hormone, vitamin D3, and prostanoids comprise a large family of sequence-specific transcription factors. They play diverse roles in development, differentiation and homeostasis by modulating gene transcription. Nuclear receptors thought to mediate their transcriptional effects in concert with coregulator proteins that modulate receptor interactions with components of the basal transcription machinery.
To date several co-factors have been isolated and characterized. Recent biochemical and genetic studies support the notion that hyperacetylation of core histones is a characteristic of gene activation, and, conversely, histone deacetylation is involved in transcriptional repression. Nuclear receptor co-repressors SMRT and N-CoR form complexes with Sin3 and histone deacetylase proteins, suggesting that chromatin remodeling by histone deacetylation is a possible mechanism for receptor mediated repression. It was found that CBP and p300 interact functionally with a human histone acetyltransferase protein P/CAF. Therefore, it appears that CBP/p300 and its associated protein P/CAF play a pivotal role in the ligand dependent transcriptional regulation and function through targeted modification of the chromatin structure. These co-factors, however, are common among the nuclear receptors. The purpose of this project is to identify the selective nuclear receptor cofactors using a novel cloning system.
To identify potential coregulators, we applied the T7 phage display system. The receptor fusioned with glutathione-S-transferase were used to isolate proteins capable of binding the receptor. The peptide from cDNA are expressed on the surface of each phage particle, and target cDNA can be amplified and enriched by binding to target nuclear receptor and passing-through irrelevant receptor.
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