Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of protein phosphatase 2A in response to phenobarbital.
The nuclear receptor CAR, a phenobarbital (PB)-responsive transcription factor, translocates into the nucleus of hepatocytes after PB induction. In non-induced mice, CAR forms a physical complex with heat shock protein 90 (HSP90) in the cytoplasm. In response to PB induction, protein phosphatase 2A is recruited to the CAR:HSP90 complex. This recruitment may lead CAR to translocate into the nucleus, consistent with the inhibitions of nuclear CAR accumulation in PB-induced mouse primary hepatocytes by okadaic acid as well as by geldanamycin.
Yoshinari
Kouichi
K
Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Kobayashi
Kaoru
K
Moore
Rick
R
Kawamoto
Takeshi
T
Negishi
Masahiko
M
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D000090702:Constitutive Androstane Receptor; D003600:Cytosol / Q000737:chemistry; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000737:chemistry / Q000648:ultrastructure; D008099:Liver / Q000737:chemistry* / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D021381:Protein Transport / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D000090702:Constitutive Androstane Receptor; D018841:HSP90 Heat-Shock Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D010634:Phenobarbital