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PPAR Research
Volume 2010, Article ID 250126, 21 pages
http://dx.doi.org/10.1155/2010/250126
Review Article

Coactivators in PPAR-Regulated Gene Expression

1Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA

Received 11 May 2010; Accepted 1 July 2010

Academic Editor: Yaacov Barak

Copyright © 2010 Navin Viswakarma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Peroxisome proliferator-activated receptor (PPAR)α, β (also known as δ), and γ function as sensors for fatty acids and fatty acid derivatives and control important metabolic pathways involved in the maintenance of energy balance. PPARs also regulate other diverse biological processes such as development, differentiation, inflammation, and neoplasia. In the nucleus, PPARs exist as heterodimers with retinoid X receptor-α bound to DNA with corepressor molecules. Upon ligand activation, PPARs undergo conformational changes that facilitate the dissociation of corepressor molecules and invoke a spatiotemporally orchestrated recruitment of transcription cofactors including coactivators and coactivator-associated proteins. While a given nuclear receptor regulates the expression of a prescribed set of target genes, coactivators are likely to influence the functioning of many regulators and thus affect the transcription of many genes. Evidence suggests that some of the coactivators such as PPAR-binding protein (PBP/PPARBP)/thyroid hormone receptor-associated protein 220 (TRAP220)/mediator complex subunit 1 (MED1) may exert a broader influence on the functions of several nuclear receptors and their target genes. Investigations into the role of coactivators in the function of PPARs should strengthen our understanding of the complexities of metabolic diseases associated with energy metabolism.