PT  - JOURNAL ARTICLE
AU  - Yuichiro Kanno
AU  - Yuki Kure
AU  - Saori Kobayashi
AU  - Mariko Mizuno
AU  - Yumi Tsuchiya
AU  - Naoya Yamashita
AU  - Kiyomitsu Nemoto
AU  - Yoshio Inouye
TI  - The tripartite motif containing 24 acts as a novel coactivator of the constitutive active/androstane receptor
AID  - 10.1124/dmd.117.077693
DP  - 2017 Jan 01
TA  - Drug Metabolism and Disposition
PG  - dmd.117.077693
4099  - http://dmd.aspetjournals.org/content/early/2017/11/03/dmd.117.077693.short
4100  - http://dmd.aspetjournals.org/content/early/2017/11/03/dmd.117.077693.full
AB  - The constitutive active/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 co-regulators, including coactivators and corepressors. In this study, tripartite motif containing 24 (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 (DR4) motif, a binding site of the CAR. This enhancement was synergistically augmented in the presence of SRC1 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 the 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.