Redundant enhancement of mouse constitutive androstane receptor transactivation by p160 coactivator family members

Jun Xia, Lan Liao, Joy Sarkar, Kojiro Matsumoto, Janardan K. Reddy, Jianming Xu, Byron Kemper

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)49-57
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume468
Issue number1
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

Keywords

  • Cellular localization
  • Cytochrome P450
  • Hepatic gene expression
  • In vivo transfection
  • Phenobarbital
  • p160-Null mice

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