PMID- 25721668 OWN - NLM STAT- MEDLINE DCOM- 20150625 LR - 20211203 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 459 IP - 1 DP - 2015 Mar 27 TI - Protein arginine methyltransferase 5 (PRMT5) is a novel coactivator of constitutive androstane receptor (CAR). PG - 143-7 LID - S0006-291X(15)00313-7 [pii] LID - 10.1016/j.bbrc.2015.02.085 [doi] AB - 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 protein arginine methyltransferase 5 (PRMT5) is a novel CAR-interacting protein. Furthermore, the PRMT-dependent induction of a CAR reporter gene, which was independent of methyltransferase activity, was enhanced in the presence of steroid receptor coactivator 1 (SRC1), peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) or DEAD box DNA/RNA helicase DP97. Using tetracycline inducible-hCAR system in HepG2 cells, we showed that knockdown of PRMT5 with small interfering RNA suppressed tetracycline -induced mRNA expression of CYP2B6 but not of CYP2C9 or CYP3A4. PRMT5 enhanced phenobarbital-mediated transactivation of a phenobarbital-responsive enhancer module (PBREM)-driven reporter gene in co-operation with PGC-1alpha in rat primary hepatocytes. Based on these findings, we suggest PRMT5 to be a gene (or promoter)-selective coactivator of CAR by mediating the formation of complexes between hCAR and appropriate coactivators. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Kanno, Yuichiro AU - Kanno Y AD - Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. Electronic address: ykanno@phar.toho-u.ac.jp. FAU - Inajima, Jun AU - Inajima J AD - Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. FAU - Kato, Sayaka AU - Kato S AD - Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. FAU - Matsumoto, Maika AU - Matsumoto M AD - Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. FAU - Tokumoto, Chikako AU - Tokumoto C AD - Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. FAU - Kure, Yuki AU - Kure Y AD - Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. FAU - Inouye, Yoshio AU - Inouye Y AD - Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150223 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Constitutive Androstane Receptor) RN - 0 (Neoplasm Proteins) RN - 0 (PPARGC1A protein, human) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Transcription Factors) RN - EC 1.14.13.- (CYP2C9 protein, human) RN - EC 1.14.13.- (Cytochrome P-450 CYP2C9) RN - EC 1.14.14.1 (CYP2B6 protein, human) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2B6) RN - EC 1.14.14.1 (Cytochrome P-450 CYP3A) RN - EC 1.14.14.55 (CYP3A4 protein, human) RN - EC 2.1.1.319 (PRMT5 protein, human) RN - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.7.7.- (DDX54 protein, human) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - Cell Line MH - Constitutive Androstane Receptor MH - Cytochrome P-450 CYP2B6/genetics/metabolism MH - Cytochrome P-450 CYP2C9/genetics/metabolism MH - Cytochrome P-450 CYP3A/genetics/metabolism MH - DEAD-box RNA Helicases/genetics/metabolism MH - Gene Expression Regulation MH - Gene Knockdown Techniques MH - Humans MH - Neoplasm Proteins/genetics/metabolism MH - Nuclear Receptor Coactivator 1/genetics/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MH - Protein-Arginine N-Methyltransferases/genetics/*metabolism MH - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism MH - Transcription Factors/genetics/metabolism MH - Transcriptional Activation OTO - NOTNLM OT - CAR OT - CYP2B6 OT - CYP3A4 OT - Nuclear receptor OT - PRMT5 EDAT- 2015/02/28 06:00 MHDA- 2015/06/26 06:00 CRDT- 2015/02/28 06:00 PHST- 2015/02/10 00:00 [received] PHST- 2015/02/13 00:00 [accepted] PHST- 2015/02/28 06:00 [entrez] PHST- 2015/02/28 06:00 [pubmed] PHST- 2015/06/26 06:00 [medline] AID - S0006-291X(15)00313-7 [pii] AID - 10.1016/j.bbrc.2015.02.085 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2015 Mar 27;459(1):143-7. doi: 10.1016/j.bbrc.2015.02.085. Epub 2015 Feb 23.