Previous Article | Next Article ![]()
Molecular and Cellular Biology, September 1999, p. 6318-6322, Vol. 19, No. 9
Pharmacogenetics Section, Laboratory of
Reproductive and Developmental Toxicology, National Institute of
Environmental Health Sciences, National Institutes of Health, Research
Triangle Park, North Carolina 27709
Received 16 April 1999/Returned for modification 1 June
1999/Accepted 16 June 1999
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.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Phenobarbital-Responsive Nuclear Translocation of
the Receptor CAR in Induction of the CYP2B Gene
*
Corresponding author. Mailing address: Laboratory of
Reproductive and Developmental Toxicology, National Institute of
Environmental Health Sciences, National Institutes of Health, Research
Triangle Park, NC 27709. Phone: (919) 541-2404. Fax: (919) 541-0696. E-mail: negishi{at}niehs.nih.gov.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|