2018 Fiscal Year Final Research Report
The mechanism of selective gene regulation Xenobiotic receptor CAR
Project/Area Number |
16K08351
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Environmental and hygienic pharmacy
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Research Institution | Toho University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Keywords | 核内受容体 / 受容体型転写因子 / 遺伝子発現調節 / 転写共役因子 / 異物代謝 / 構成的アンドロスタン受容体 |
Outline of Final Research Achievements |
The constitutive active/androstane receptor (CAR) controls genes involved in xenochemical metabolism. Although numerous cofactors have been reported to be involved in CAR-mediated transactivation, unknown and poorly defined proteins recruited by CAR have yet to be characterized. In this study, a novel CAR-interacting proteins, cell cycle and apoptosis regulator 1 (CCAR1) and Tripartite Motif Containing 24(TRIM24), were identified as novel CAR binding proteins. Furthermore, knock down of these cofactors are showed different effect of CAR-induced transactivation. These findings demonstrated CCAR1 and TRIM24 to be novel transcriptional cofactors for CAR and provided insight regarding the mechanism of CAR-mediated gene-selective transactivation.
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Free Research Field |
衛生薬学、分子生物学
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Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により、まだ不明な点が多い受容体型転写因子による遺伝子選択的な発現調節機構の一端が明らかとなった。受容体型転写因子である核内受容体による選択遺伝子発現機構の解明は、選択的核内受容体調節薬のような作用を選択的に利用できる医薬品の開発の一助になると考えている。
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