RT Journal Article SR Electronic T1 Phenobarbital-Responsive Nuclear Translocation of the Receptor CAR in Induction of the CYP2B Gene JF Molecular and Cellular Biology JO Mol. Cell. Biol. FD American Society for Microbiology SP 6318 OP 6322 DO 10.1128/MCB.19.9.6318 VO 19 IS 9 A1 Kawamoto, Takeshi A1 Sueyoshi, Tatsuya A1 Zelko, Igor A1 Moore, Rick A1 Washburn, Kimberly A1 Negishi, Masahiko YR 1999 UL http://mcb.asm.org/content/19/9/6318.abstract AB The constitutively active receptor (CAR) transactivates a distal enhancer called the phenobarbital (PB)-responsive enhancer module (PBREM) found in PB-inducible CYP2B genes. CAR dramatically increases its binding to PBREM in livers of PB-treated mice. We have investigated the cellular mechanism of PB-induced increase of CAR binding. Western blot analyses of mouse livers revealed an extensive nuclear accumulation of CAR following PB treatment. Nuclear contents of CAR perfectly correlate with an increase of CAR binding to PBREM. PB-elicited nuclear accumulation of CAR appears to be a general step regulating the induction of CYP2B genes, since treatments with other PB-type inducers result in the same nuclear accumulation of CAR. Both immunoprecipitation and immunohistochemistry studies show cytoplasmic localization of CAR in the livers of nontreated mice, indicating that CAR translocates into nuclei following PB treatment. Nuclear translocation of CAR also occurs in mouse primary hepatocytes but not in hepatocytes treated with the protein phosphatase inhibitor okadaic acid. Thus, the CAR-mediated transactivation of PBREM in vivo becomes PB responsive through an okadaic acid-sensitive nuclear translocation process.