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Sci. Signal., 2 December 2008
Vol. 1, Issue 48, p. pe52
[DOI: 10.1126/scisignal.148pe52]

PERSPECTIVES

Ligand-Dependent and -Independent Regulation of PPAR{gamma} and Orphan Nuclear Receptors

H. Eric Xu1* and Yong Li2*

1 Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Northeast, Grand Rapids, MI 49503, USA.
2 Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, 709 Salk Hall, Pittsburgh, PA 15261, USA.

Abstract: Peroxisome proliferator–activated receptor {gamma} (PPAR{gamma}) is considered to be a ligand-activated nuclear receptor with essential roles in adipogenesis, glucose and lipid homeostasis, and inflammatory responses. An unusually large ligand-binding pocket is a distinguishing feature of PPAR{gamma} and two related receptors, PPAR{alpha} and PPARβ (also known as PPAR{delta}), which allows these receptors to interact with diverse chemical ligands including various fatty acids, fibrates, and the thiazolidinedione class of antidiabetic drugs. However, the physiologically relevant ligand of PPARs remains unknown. A PPAR{gamma} mutant that is incapable of binding ligands unexpectedly directed adipogenesis when introduced into fibroblasts. This raises key issues regarding the existence and roles of the hypothetical physiological ligands for PPAR{gamma}, issues that may also apply to other "orphan" nuclear receptors lacking bona fide ligands. Identification of the physiological ligands of PPARs and orphan nuclear receptors will be crucial for understanding the biology of these receptors.

* Corresponding authors. E-mail, eric.xu{at}vai.org (H.E.X.); yol21{at}pitt.edu (Y.L.)

Citation: H. E. Xu, Y. Li, Ligand-Dependent and -Independent Regulation of PPAR{gamma} and Orphan Nuclear Receptors. Sci. Signal. 1, pe52 (2008).

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