Journal of receptor and signal transduction research
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J. Recept. Signal Transduct. Res. · Jan 2006
ReviewControl of peroxisome proliferator-activated receptor fate by the ubiquitinproteasome system.
Peroxisome proliferator-activated receptor (PPAR) alpha, gamma, and delta belong to the nuclear hormone receptor superfamily of ligand-activated transcription factors. PPARs regulate metabolic, developmental, and differentiation pathways and play important roles in human diseases, such as diabetes, atherosclerosis, cancer, and chronic inflammation. PPARs are the targets of drugs of widespread clinical use and represent promising targets for discovery of new therapeutics. ⋯ The UPS plays an important role in regulating the levels and modulating ligand-dependent and-independent activity of nuclear receptors. This review highlights the current knowledge regarding the interactions of the UPS with PPARs and focuses on the differential regulation of the level and activity of the PPAR isotypes by the UPS in response to selective ligands. Understanding the connections between the UPS and PPARs can provide insights in the actions of existing drugs and raise the possibilities for development of more effective PPAR-based therapeutics.