Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor

Yijun Zhu, Chao Qi, Sanjay Jain, M. Sambasiva Rao, Janardan K. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

293 Scopus citations

Abstract

In an attempt to identify cofactors that could possibly influence the transcriptional activity of peroxisome proliferator-activated receptors (PPARs), we used a yeast two-hybrid system with Ga14-PPARγ as bait to screen a mouse liver cDNA library and have identified steroid receptor coactivator- 1 (SRC-1) as a PPAR transcriptional coactivator. We now report the isolation of a cDNA encoding a 165-kDa PPARγ-binding protein, designated PBP which also serves as a coactivator. PBP also binds to PPARα, RARα, RXR, and TRβ1, and this binding is increased in the presence of specific ligands. Deletion of the last 12 amino acids from the carboxyl terminus of PPARγ results in the abolition of interaction between PBP and PPARγ. PBP modestly increased the transcriptional activity of PPARγ, and a truncated form of PBP (amino acids 487-735) acted as a dominant-negative repressor, suggesting that PBP is a genuine coactivator for PPAR. In addition, PBP contains two LXXLL signature motifs considered necessary and sufficient for the binding of several coactivators to nuclear receptors. In situ hybridization and Northern analysis showed that PBP is expressed in many tissues of adult mice, including the germinal epithelium of testis, where it appeared most abundant, and during ontogeny, suggesting a possible role for this cofactor in cellular proliferation and differentiation.

Original languageEnglish (US)
Pages (from-to)25500-25506
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number41
DOIs
StatePublished - Oct 10 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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