2014 Fiscal Year Final Research Report
Analysis to elucidate regulatory mechanism of LXR in uterine tissue
Project/Area Number |
24592505
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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 |
Obstetrics and gynecology
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Research Institution | The University of Tokyo |
Principal Investigator |
HIRAIKE Osamu 東京大学, 医学部附属病院, 講師 (20529060)
|
Co-Investigator(Kenkyū-buntansha) |
ODA Katsutoshi 東京大学医学部附属病院, 女性外科, 准教授 (30359068)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Keywords | 核内受容体 / 転写因子 / 乳がん / 子宮体がん |
Outline of Final Research Achievements |
Liver X receptors (LXRs) have been shown to maintain whole-body cholesterol level. Recent studies demonstrate that LXRs might inhibit cellular proliferation, but the underlying mechanism remains to be elucidated. We found that CCAR2 could form a complex with LXRα in a ligand-independent manner in HepG2 cells, and in vitro pull down assays revealed a direct interaction between the amino-terminus of CCAR2 and AF-2 domain of LXRα. Thereby CCAR2 attenuates the ligand-dependent transcriptional activation function of LXRα. Abrogation of CCAR2 resulted in a decreased cellular proliferation. Competitive immunoprecipitation studies have revealed that the downregulation of LXRα involves inhibition of SIRT1 interaction with LXRα. These results clearly indicate the mechanism that CCAR2 might regulate the transcriptional activation function of LXRα due to its specific inhibition of SIRT1 and serve to regulate the cellular proliferation.
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Free Research Field |
生殖生理
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