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Association with coregulators is the major determinant governing peroxisome proliferator-activated receptor mobility in living cells.

Authors
  • Tudor, Cicerone
  • Feige, Jérôme N
  • Pingali, Harikishore
  • Lohray, Vidya Bhushan
  • Wahli, Walter
  • Desvergne, Béatrice
  • Engelborghs, Yves
  • Gelman, Laurent
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publication Date
Feb 16, 2007
Volume
282
Issue
7
Pages
4417–4426
Identifiers
PMID: 17164241
Source
Medline
License
Unknown

Abstract

The nucleus is an extremely dynamic compartment, and protein mobility represents a key factor in transcriptional regulation. We showed in a previous study that the diffusion of peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptors regulating major cellular and metabolic functions, is modulated by ligand binding. In this study, we combine fluorescence correlation spectroscopy, dual color fluorescence cross-correlation microscopy, and fluorescence resonance energy transfer to dissect the molecular mechanisms controlling PPAR mobility and transcriptional activity in living cells. First, we bring new evidence that in vivo a high percentage of PPARs and retinoid X receptors is associated even in the absence of ligand. Second, we demonstrate that coregulator recruitment (and not DNA binding) plays a crucial role in receptor mobility, suggesting that transcriptional complexes are formed prior to promoter binding. In addition, association with coactivators in the absence of a ligand in living cells, both through the N-terminal AB domain and the AF-2 function of the ligand binding domain, provides a molecular basis to explain PPAR constitutive activity.

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