Abstract
The constitutive androstane receptor (CAR) plays a key role in the expression of xenobiotic/steroid and drug metabolizing enzymes and their transporters. In this study, we demonstrated that DP97, a member of the DEAD box DNA/RNA helicase protein family, is a novel CAR-interacting protein. Using HepG2 cells expressing human CAR in the presence of tetracycline, we showed that knockdown of DP97 with small interfering RNAs suppressed tetracycline-inducible mRNA expression of CYP2B6 and UGT1A1 but not CYP3A4. Thus, DP97 was found to be a gene (or promoter)-selective co-activator for hCAR. DP97-mediated CAR transactivation was synergistically enhanced by the co-expression of SRC-1 or PGC1α, therefore it might act as mediator between hCAR and appropriate co-activators.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Constitutive Androstane Receptor
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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HEK293 Cells
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism
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Humans
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nuclear Receptor Coactivator 1 / genetics
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Nuclear Receptor Coactivator 1 / metabolism
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Receptors, Cytoplasmic and Nuclear / genetics*
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Receptors, Cytoplasmic and Nuclear / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Activation*
Substances
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Constitutive Androstane Receptor
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Heat-Shock Proteins
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Neoplasm Proteins
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PPARGC1A protein, human
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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NCOA1 protein, human
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Nuclear Receptor Coactivator 1
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DDX54 protein, human
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DEAD-box RNA Helicases