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• W2138506509 abstract "A previous report demonstrated that treatment of human hepatocytes with phenobarbital, an activator of nuclear receptor constitutive androstane receptor (CAR), increases mRNA levels of an efflux transporter ABCG2, which is involved in the excretion of xenobiotics in liver and intestine. The results suggest that human CAR (hCAR) transactivates human ABCG2 (hABCG2) expression. In this study, we confirmed increase in ABCG2 mRNA levels in human hepatocytes after adenoviral expression of hCAR and treatment with its activator. Reporter assays suggested the existence of an hCAR-responsive element between −8000 and −7485 of hABCG2 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays identified a DR5 motif (direct repeat separated by five nucleotides) within the region as a binding motif of hCAR/human retinoid X receptor α heterodimer. The introduction of mutations into the DR5 motif resulted in the complete loss of the hCAR-mediated transactivation. Interestingly, human pregnane X receptor, belonging to the same NR1I subfamily as CAR, did not activate any reporter gene containing the DR5 motif. Taken together, our present findings suggest that hCAR transactivates hABCG2 through the DR5 motif located in its distal promoter in human hepatocytes and that the motif prefers hCAR to pregnane X receptor." @default.
• W2138506509 created "2016-06-24" @default.
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• W2138506509 date "2012-01-01" @default.
• W2138506509 modified "2023-10-09" @default.
• W2138506509 title "Transactivation of ABCG2 through a novel cis-element in the distal promoter by constitutive androstane receptor but not pregnane X receptor in human hepatocytes" @default.
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• W2138506509 doi "https://doi.org/10.1016/j.abb.2011.10.014" @default.
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