Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR

Yijun Zhu, Lixin Kan, Chao Qi, Yashpal S. Kanwar, Anjana V. Yeldandi, M. Sambasiva Rao, Janardan K. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

We previously isolated and identified steroid receptor coactivator-1 (SRC-1) and peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP/PPARBP) as coactivators for PPAR, using the ligand-binding domain of PPARγ, as bait in a yeast two-hybrid screening. As part of our continuing effort to identify cofactors that influence the transcriptional activity of PPARs, we now report the isolation of a novel coactivator from mouse, designated PRIP (peroxisome proliferator-activated receptor interacting protein), a nuclear protein with 2068 amino acids and encoded by 13 exons. Northern analysis showed that PRIP mRNA is ubiquitously expressed in many tissues of adult mice. PRIP contains two LXXLL signature motifs. The amino- terminal LXXL motif (amino acid position 892 to 896) of PRIP was found to be necessary for nuclear receptor interaction, but the second LXX motif (amino acid position 1496 to 1500) appeared unable to bind PPARγ. Deletion of the last 12 amino acids from the carboxyl terminus of PPARγ resulted in the abolition of the interaction between PRIP and PPARγ. PRIP also binds to PPARα, RARα, RXRα, ER, and TRβ1, and this binding is increased in the presence of specific ligands. PRIP acts as a strong coactivator for PPARγ in the yeast and also potentiates the transcriptional activities of PPARγ and RXRα in mammalian cells. A truncated form of PRIP (amino acids 786-1132) acts as a dominant-negative repressor, suggesting that PRIP is a genuine coactivator.

Original languageEnglish (US)
Pages (from-to)13510-13516
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number18
DOIs
StatePublished - May 5 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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