Tripartite Motif Containing 24 Acts as a Novel Coactivator of the Constitutive Active/Androstane Receptor.

The constitutive androstane receptor (CAR) is a nuclear receptor that acts as a transcription factor for a variety of genes, including genes encoding xenobiotic, steroid, and drug-metabolizing enzymes and transporters. Transactivation of a target gene by a transcription factor is generally mediated through the concerted and stepwise recruitment of various ...
proteins termed coregulators, including coactivators and corepressors. In this study, TRIM24 (also known as transcriptional intermediary factor 1 alpha) was found to interact with the CAR. TRIM24 enhanced the CAR-dependent transactivation in reporter assays using the direct repeat-4 motif, a binding site of the CAR. This enhancement was synergistically augmented in the presence of steroid receptor coactivator (SRC) 1 or SRC2, both of which are coactivators of the CAR. In addition, TRIM24 was recruited to the CAR-binding element of the CYP2B6 promoter together with the CAR. We also noted that knockdown of TRIM24 suppressed CAR-induced CYP2B6 mRNA expression in HepTR/CAR and HepaRG cells and suppressed CAR-induced CYP3A4 mRNA expression in HepaRG cells but not HepTR/CAR cells. From these results, we suggest that TRIM24 is a novel coactivator of the CAR that is involved in cell- and/or promoter- selective transactivation.
Mesh Terms:
Carrier Proteins, Cytochrome P-450 CYP2B6, Cytochrome P-450 CYP3A, Gene Knockdown Techniques, Hep G2 Cells, Humans, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 2, Promoter Regions, Genetic, RNA Interference, RNA, Messenger, RNA, Small Interfering, Receptors, Cytoplasmic and Nuclear, Transcriptional Activation
Drug Metab. Dispos.
Date: Dec. 01, 2017
Download Curated Data For This Publication
214135
Switch View:
  • Interactions 4