Redundant Enhancement of Mouse Constitutive Androstane Receptor Transactivation by p160 Coactivator Family Members

Arch Biochem Biophys. 2007 Dec 1;468(1):49-57. doi: 10.1016/j.abb.2007.09.005. Epub 2007 Sep 18.

Abstract

Constitutive androstane receptor (CAR) transactivation is enhanced by p160 coactivators, which include three members, SRC-1, SRC-2, and SRC-3. Each of the p160 coactivators enhanced mouse CAR (mCAR) transactivation of the CYP2B1 phenobarbital (PB)-responsive enhancer in transfected cultured cells and mouse hepatocytes in vivo. The cellular localization of the p160 coactivators in hepatocytes in vivo was not altered by PB treatment, nor did any of the p160 coactivators selectively colocalize with mCAR in the nucleus. Exogenous expression of each p160 coactivator mediated the PB-independent nuclear accumulation of mCAR in hepatocytes in vivo. Induction of Cyp2b10 gene expression by PB was equivalent or greater in mice null for each of the p160 coactivators than in wild type mice. These results indicate that the p160 coactivators are redundant with regard to enhancing CAR-mediated induction of cytochrome P450 genes. SRC-3 alone of the p160 coactivators enhanced CAR transactivation in hepatic cells without PB treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • DNA-Binding Proteins
  • Hepatocytes / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation / physiology*

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Mybbp1a protein, mouse
  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Transcription Factors
  • constitutive androstane receptor