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Int. J. Mol. Sci. 2018, 19(6), 1738; https://doi.org/10.3390/ijms19061738

Functional Regulation of PPARs through Post-Translational Modifications

1
Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore
2
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Singapore 138673, Singapore
3
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117596, Singapore
*
Author to whom correspondence should be addressed.
Received: 3 May 2018 / Revised: 5 June 2018 / Accepted: 7 June 2018 / Published: 12 June 2018
(This article belongs to the Special Issue PPARs in Cellular and Whole Body Energy Metabolism)
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Abstract

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily and they are essential regulators of cell differentiation, tissue development, and energy metabolism. Given their central roles in sensing the cellular metabolic state and controlling metabolic homeostasis, PPARs became important targets of drug development for the management of metabolic disorders. The function of PPARs is mainly regulated through ligand binding, which induces structural changes, further affecting the interactions with co-activators or co-repressors to stimulate or inhibit their functions. In addition, PPAR functions are also regulated by various Post-translational modifications (PTMs). These PTMs include phosphorylation, SUMOylation, ubiquitination, acetylation, and O-GlcNAcylation, which are found at numerous modification sites. The addition of these PTMs has a wide spectrum of consequences on protein stability, transactivation function, and co-factor interaction. Moreover, certain PTMs in PPAR proteins have been associated with the status of metabolic diseases. In this review, we summarize the PTMs found on the three PPAR isoforms PPARα, PPARβ/δ, and PPARγ, and their corresponding modifying enzymes. We also discuss the functional roles of these PTMs in regulating metabolic homeostasis and provide a perspective for future research in this intriguing field. View Full-Text
Keywords: nuclear receptors; PPARα; PPARγ; PPARβ/δ; post-translational modifications nuclear receptors; PPARα; PPARγ; PPARβ/δ; post-translational modifications
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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. (CC BY 4.0).
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Brunmeir, R.; Xu, F. Functional Regulation of PPARs through Post-Translational Modifications. Int. J. Mol. Sci. 2018, 19, 1738.

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