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PMID: 12189208 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 18 ·2002-09-03 ·Pages 11836-41

Surapureddi S, Yu S, Bu H, Hashimoto T, Yeldandi AV, Kashireddy P, Cherkaoui-Malki M, Qi C, Zhu YJ, Rao MS, Reddy JK

Abstract

Peroxisome proliferator-activated receptor alpha (PPAR alpha) 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 PPAR alpha-interacting cofactor (PRIC) complex from rat liver nuclear extracts that interacts with full-length PPAR alpha in the presence of ciprofibrate, a synthetic ligand, and leukotriene B(4), a natural ligand. The liganded PPAR alpha-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 PPAR alpha and acts as a coactivator by moderately stimulating PPAR alpha-mediated transcription in transfected cells. We conclude that liganded PPAR alpha 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.

MeSH Terms
Amino Acid Sequence Animals Cloning, Molecular DNA, Complementary Liver/metabolism Male Molecular Sequence Data Rats Rats, Inbred F344 Receptors, Cytoplasmic and Nuclear/metabolism Trans-Activators/chemistry,genetics,metabolism Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA, Complementary Helz2 protein, rat Receptors, Cytoplasmic and Nuclear Trans-Activators Transcription Factors
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Surapureddi Sailesh
Department of Pathology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA.
Yu Songtao
Bu Hengfu
Hashimoto Takashi
Yeldandi Anjana V
Kashireddy Papreddy
Cherkaoui-Malki Mustapha
Qi Chao
Zhu Yi-Jun
Rao M Sambasiva
Reddy Janardan K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.182426699
Published
2002-09-03
Epub
2002-00-20
Pages
11836-41
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC129355
Subset
IM
Grants
NIGMS NIH HHS · GM23570 · United States
NCI NIH HHS · CA84472 · United States
NIGMS NIH HHS · R37 GM023750 · United States
NCI NIH HHS · R01 CA084472 · United States
NIGMS NIH HHS · R01 GM023750 · United States
Databases
GENBANK
AF517673
External Links
PubMed source DOI: 10.1073/pnas.182426699 PMC Full Text View journal details
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