RGD Reference Report - Identification of a transcriptionally active peroxisome proliferator-activated receptor alpha -interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator. - Rat Genome Database

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

Authors: Surapureddi, S  Yu, S  Bu, H  Hashimoto, T  Yeldandi, AV  Kashireddy, P  Cherkaoui-Malki, M  Qi, C  Zhu, YJ  Rao, MS  Reddy, JK 
Citation: Surapureddi S, etal., Proc Natl Acad Sci U S A 2002 Sep 3;99(18):11836-41.
RGD ID: 729665
Pubmed: PMID:12189208   (View Abstract at PubMed)
PMCID: PMC129355   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.182426699   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kat6bRatpositive regulation of transcription by RNA polymerase II  IDA  RGD 
PparaRatregulation of DNA-templated transcription  IDA  RGD 
PparaRatregulation of fatty acid metabolic process  TAS  RGD 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Kat6b  (lysine acetyltransferase 6B)
Med24  (mediator complex subunit 24)
Ncoa6  (nuclear receptor coactivator 6)
Ppara  (peroxisome proliferator activated receptor alpha)

Objects referenced in this article
Gene Chd5 chromodomain helicase DNA binding protein 5 Rattus norvegicus
Gene Med1 mediator complex subunit 1 Rattus norvegicus

Additional Information