| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| 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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