Transcription coactivator PRIP, the Peroxisome Proliferator-Activated Receptor (PPAR)-interacting protein, is redundant for the function of nuclear receptors PPARα and CAR, the constitutive androstane receptor, in mouse liver

Joy Sarkar, Chao Qi, Dongsheng Guo, Mohamed R. Ahmed, Yuzhi Jia, Nobuteru Usuda, Navin Viswakarma, Sambasiva Rao Musunuri, Janardan K Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Disruption of the genes encoding for the transcription coactivators, peroxisome proliferator-activated receptor (PPAR)-interacting protein (PRIP/ASC-2/RAP250/ TRBP/NRC) and PPAR-binding protein (PBP/TRAP220/DRIP205/ MED1), results in embryonic lethality by affecting placental and multiorgan development. Targeted deletion of coactivator PBP gene in liver parenchymal cells (PBPLiv-/-) results in the near abrogation of the induction of PPARα and CAR (constitutive androstane receptor)-regulated genes in liver. Here, we show that targeted deletion of coactivator PRIP gene in liver (PRIPLiv-/-) does not affect the induction of PPARα-regulated pleiotropic responses, including hepatomegaly, hepatic peroxisome proliferation, and induction of mRNAs of genes involved in fatty acid oxidation system, indicating that PRIP is not essential for PPARα-mediated transcriptional activity. We also provide additional data to show that liver-specific deletion of PRIP gene does not interfere with the induction of genes regulated by nuclear receptor CAR. Furthermore, disruption of PRIP gene in liver did not alter zoxazolamine-induced paralysis, and acetaminophen-induced hepatotoxicity. Studies with adenovirally driven EGFP-CAR expression in liver demonstrated that, unlike PBP, the absence of PRIP does not prevent phenobarbital-mediated nuclear translocation/retention of the receptor CAR in liver in vivo and cultured hepatocytes in vitro. These results show that PRIP deficiency in liver does not interfere with the function of nuclear receptors PPARα and CAR. The dependence of PPARα- and CAR-regulated gene transcription on coactivator PBP but not on PRIP attests to the existence of coactivator selectivity in nuclear receptor function.

Original languageEnglish (US)
Pages (from-to)255-269
Number of pages15
JournalGene Expression
Volume13
Issue number4-5
Publication statusPublished - Jul 10 2007

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Keywords

  • CAR
  • Nuclear receptor coactivators
  • PBP/TRAP220/MED1
  • PPARα
  • PRIP

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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