Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Peroxisome proliferator-activated receptor (ppar) gamma coactivator-1 recruitment regulates ppar subtype specificity

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Oberkofler, H.
  • Esterbauer, H.
  • Linnemayr, V.
  • Strosberg, Donny
  • Krempler, F.
  • Patsch, W.

publication date

  • 2002

journal

  • Journal of Biological Chemistry  Journal

abstract

  • The peroxisome proliferator-activated receptors (PPAR) alpha and gamma play key roles in the transcriptional control of contrasting metabolic pathways such as adipogenesis and fatty acid beta-oxidation. Both ligand-activated nuclear receptors bind to common target gene response elements and interact with distinct domains of the transcriptional coactivator PGC-1 to attain their full transcriptional potency. Thus, PPAR subtype specificity may be determined by ligand availability and transcription factor or coactivator expression levels. To identify other, perhaps more precise mechanisms contributing to PPAR subtype specificity, we studied PGC-1 recruitment by PPARs using a previously described hormone response element in the human UCP1 promoter and a human brown adipocyte cell line as our model system. As in rodents, PGC-1 is involved in the transcriptional regulation of the UCP1 gene in humans and mediates the effects of PPARalpha and PPARgamma agonists and retinoic acid. Interestingly, a previously postulated PGC-1 repressor selectively affects the PPARalpha-mediated activation of UCP1 gene expression. Furthermore, inhibition of p38 MAPK signaling, known to regulate the PGC-1/repressor interaction, decreases the stimulatory effect of PPARalpha agonist treatment without reducing the response to thiazolidinedione or retinoic acid. These data support a model whereby PPAR subtype specificity is regulated by recruitment of PGC-1.

subject areas

  • Adipocytes
  • Animals
  • Base Sequence
  • Carrier Proteins
  • Cell Line
  • Cell Nucleus
  • DNA, Complementary
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • Humans
  • Imidazoles
  • Ion Channels
  • Ligands
  • MAP Kinase Signaling System
  • Membrane Proteins
  • Mitochondrial Proteins
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • Mutation
  • Oxygen
  • Plasmids
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Pyridines
  • Rats
  • Receptors, Cytoplasmic and Nuclear
  • Signal Transduction
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • Tretinoin
  • p38 Mitogen-Activated Protein Kinases
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M200475200

PubMed ID

  • 11875072
scroll to property group menus

Additional Document Info

start page

  • 16750

end page

  • 16757

volume

  • 277

issue

  • 19

©2019 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support