Identification of a transcriptionally active peroxisome proliferator-activated receptor α-interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator

Sailesh Surapureddi, Songtao Yu, Hengfu Bu, Takashi Hashimoto, Anjana V Yeldandi, Papreddy Kashireddy, Mustapha Cherkaoui-Malki, Chao Qi, Yijun Zhu, Sambasiva Rao Musunuri, Janardan K Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Peroxisome proliferator-activated receptor α (PPARα) plays a central role in the cell-specific pleiotropic responses induced by structurally diverse synthetic chemicals designated as peroxisome proliferators. Transcriptional regulation by liganded nuclear receptors involves the participation of cofactors that form multiprotein complexes to achieve cell- and gene-specific transcription. Here we report the identification of such a transcriptionally active PPARα-interacting cofactor (PRIC) complex from rat liver nuclear extracts that interacts with full-length PPARα in the presence of ciprofibrate, a synthetic ligand, and leukotriene B4, a natural ligand. The liganded PPARα-PRIC complex enhanced transcription from a peroxisomal enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme gene promoter template that contains peroxisome proliferator response elements. Rat liver PRIC complex comprises some 25 polypeptides, and their identities were established by mass spectrometry and limited sequence analysis. Eighteen of these peptides contain one or more LXXLL motifs necessary for interacting with nuclear receptors. PRIC complex includes known coactivators or coactivator-binding proteins (CBP, SRC-1, PBP, PRIP, PIMT, TRAP100, SUR-2, and PGC-1), other proteins that have not previously been described in association with transcription complexes (CHD5, TOG, and MORF), and a few novel polypeptides designated PRIC300. -285, -215, -177, and -145. We describe the cDNA for PRIC285, which contains five LXXLL motifs. It interacts with PPARα and acts as a coactivator by moderately stimulating PPARα-mediated transcription in transfected cells. We conclude that liganded PPARα recruits a distinctive multiprotein complex from rat liver nuclear extracts. The composition of this complex may provide insight into the basis of tissue and species sensitivity to peroxisome proliferators.

Original languageEnglish (US)
Pages (from-to)11836-11841
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number18
DOIs
StatePublished - Sep 3 2002

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Identification of a transcriptionally active peroxisome proliferator-activated receptor α-interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator'. Together they form a unique fingerprint.

  • Cite this