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

By C. Tudor, J.N. Feige, H. Pingali, V.B. Lohray, W. Wahli, B. Desvergne, Y. Engelborghs and L. Gelman

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

Topics: Animals; Fluorescence Resonance Energy Transfer; Hela Cells; Humans; Ligands; Nuclear Proteins/metabolism; Peroxisome Proliferator-Activated Receptors/metabolism; Protein Structure, Tertiary; Protein Transport; Retinoid X Receptors/metabolism
Publisher: 'American Society for Biochemistry & Molecular Biology (ASBMB)'
Year: 2007
DOI identifier: 10.1074/jbc.M608172200
OAI identifier: oai:serval.unil.ch:BIB_5E9EB7E03DD3
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