| Project/Area Number |
11672203
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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 |
Biological pharmacy
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| Research Institution | NATIONAL INSTITUTE OF PUBLIC HEALTH |
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Principal Investigator |
TOHKIN Masahiro NATIONAL INSTITUTE OF PUBLIC HEALTH, PHARMACEUTICAL SCIENCE, SENIOR RESEARCH OFFICER, 衛生薬学部, 主任研究官 (00270629)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSE Kouichi NATIONAL INSTITUTE OF PUBLIC HEALTH, PHARNACEUTICAL SCIENCE, SENIOR RESEARCH OFFICER, 衛生薬学部, 主任研究官 (30280754)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | DIOXIN / GENE EXPRESSION / CYP2A8 / CYP2A8 / マウス肝臓 / One hybrid screening / 核内因子 / AHR / XRE / ダイオキシン受容体 / 遺伝子転写活性 / 核内転写因子 |
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| Research Abstract |
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the biological responses to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Embryonic fibroblast (EF) isolated from AHR-null mice exhibited slow cell growth as compared with wild-type EF. Reintroduction of AHR into AHR-null EF increased cell growth, suggesting that AHR is involved in cell cycle control. The role of the AHR in cell cycle control was examined using the adenovirus oncoprotein E1A. EF, derived from wild-type and AHR-null mice, were transfected with two mutant E1A expression plasmids, that inactivate either p300/CBP or retinoblastoma protein (pRb). Although DNA synthesis of wild-type EF was induced by both E1A mutants, DNA synthesis in the AHR-null EF was induced only by the mutant that binds pRb but not by the mutant to p300/CBP. These data show that both pRb and p300/CBP were the target of E1A-induced DNA synthesis in wild-type EF. In AHR-null, however, only pRb was the target of E1A-induced DNA synthesis and p300/CBP cannot be inactivated by E1A in the absence of AHR. Immunoprecipitation revealed that AHR directly bound to p300 thus suggesting the intriguing possibility that AHR is involved in control of the cell cycle via interaction with p300.
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