Is PPAR<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>/<mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>δ</mml:mi></mml:math> a Retinoid Receptor?

Berry, Daniel C.; Noy, Noa

doi:https://doi.org/10.1155/2007/73256

PPAR Research

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Volume 2007 | Article ID 073256 | https://doi.org/10.1155/2007/73256

Is PPARβ/δ a Retinoid Receptor?

Daniel C. Berry¹and Noa Noy¹

Academic Editor: John P. Vanden Heuvel

Received11 Jun 2007

Accepted21 Nov 2007

Published17 Jan 2008

Abstract

The broad ligand-binding characteristic of PPARβ/δ has long hampered identification of physiologically-meaningful ligands for the receptor. The observations that the activity of PPARβ/δ is supported by fatty acid binding protein 5 (FABP5), which directly delivers ligands from the cytosol to the receptor, suggest that bona fide PPARβ/δ ligands both activate the receptor, and trigger the nuclear translocation of FABP5. Using these criteria, it was recently demonstrated that all-trans-retinoic acid (RA), the activator of the classical retinoic acid receptor RAR, also serves as a ligand for PPARβ/δ. Partitioning of RA between its two receptors was found to be regulated by FABP5, which delivers it to PPARβ/δ, and cellular RA binding protein II (CRABP-II), which targets it to RAR. Consequently, RA activates PPARβ/δ in cells that display a high FABP5/CRABP-II expression ratio. It remains to be clarified whether compounds other than RA may also serve as endogenous activators for this highly promiscuous protein.

References

D. J. Mangelsdorf and R. M. Evans, “The RXR heterodimers and orphan receptors,” Cell, vol. 83, no. 6, pp. 841–850, 1995.
View at: Publisher Site | Google Scholar
V. Bocher, G. Chinetti, J. C. Fruchart, and B. Staels, “Role of the peroxisome proliferator-activated receptors (PPARS) in the regulation of lipids and inflammation control,” Journal de la Société de Biologie, vol. 196, no. 1, pp. 47–52, 2002.
View at: Google Scholar
V. Bocher, I. Pineda-Torra, J. C. Fruchart, and B. Staels, “PPARs: transcription factors controlling lipid and lipoprotein metabolism,” Annals of the New York Academy of Sciences, vol. 967, pp. 7–18, 2002.
View at: Google Scholar
A. Chawla, J. J. Repa, R. M. Evans, and D. J. Mangelsdorf, “Nuclear receptors and lipid physiology: opening the X-files,” Science, vol. 294, no. 5548, pp. 1866–1870, 2001.
View at: Publisher Site | Google Scholar
S. A. Smith, “Peroxisomal proliferate-activated receptors and the regulation of lipid oxidation and adipogenesis,” Biochemical Society Transactions, vol. 25, no. 4, pp. 1242–1248, 1997.
View at: Google Scholar
T. M. Willson, P. J. Brown, D. D. Sternbach, and B. R. Henke, “The PPARs: from orphan receptors to drug discovery,” Journal of Medicinal Chemistry, vol. 43, no. 4, pp. 527–550, 2000.
View at: Publisher Site | Google Scholar
S. Mandard, M. Muller, and S. Kersten, “Peroxisome proliferator-activated receptor $α$ target genes,” Cellular and Molecular Life Sciences, vol. 61, no. 4, pp. 393–416, 2004.
View at: Publisher Site | Google Scholar
D. Duffy and D. J. Rader, “Drugs in development: targeting high-density lipoprotein metabolism and reverse cholesterol transport,” Current Opinion in Cardiology, vol. 20, no. 4, pp. 301–306, 2005.
View at: Publisher Site | Google Scholar
M. A. Lazar, “PPAR $γ$ , 10 years later,” Biochimie, vol. 87, no. 1, pp. 9–13, 2005.
View at: Publisher Site | Google Scholar
M. Lehrke and M. A. Lazar, “The many faces of PPAR $γ$ ,” Cell, vol. 123, no. 6, pp. 993–999, 2005.
View at: Publisher Site | Google Scholar
J. M. Lehmann, L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer, “An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor $γ$ (PPAR $γ$ ),” Journal of Biological Chemistry, vol. 270, no. 22, pp. 12953–12956, 1995.
View at: Publisher Site | Google Scholar
B. Desvergne and W. Wahli, “Peroxisome proliferator-activated receptors: nuclear control of metabolism,” Endocrine Reviews, vol. 20, no. 5, pp. 649–688, 1999.
View at: Publisher Site | Google Scholar
P. R. Devchand, H. Keller, J. M. Peters, M. Vazquez, F. J. Gonzalez, and W. Wahli, “The PPAR $α$ -leukotriene B4 pathway to inflammation control,” Nature, vol. 384, no. 6604, pp. 39–43, 1996.
View at: Publisher Site | Google Scholar
B. M. Forman, E. Goode, J. Chen et al., “Identification of a nuclear receptor that is activated by farnesol metabolites,” Cell, vol. 81, no. 5, pp. 687–693, 1995.
View at: Publisher Site | Google Scholar
J. M. Peters, S. S. Lee, W. Li et al., “Growths, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor $ß$ ( $d$ ),” Molecular and Cellular Biology, vol. 20, no. 14, pp. 5119–5128, 2000.
View at: Publisher Site | Google Scholar
A. Cimini, L. Cristiano, A. Bernardo, E. Benedetti, S. D. I. Loreto, and M. P. Ceru, “Peroxisomes and PPARs in cultured neural cells,” Advances in Experimental Medicine and Biology, vol. 544, pp. 271–280, 2003.
View at: Google Scholar
N. S. Tan, L. Michalik, B. Desvergne, and W. Wahli, “Peroxisome proliferator-activated receptor- $β$ as a target for wound healing drugs,” Expert Opinion on Therapeutic Targets, vol. 8, no. 1, pp. 39–48, 2004.
View at: Publisher Site | Google Scholar
N. S. Tan, L. Michalik, N. Noy et al., “Critical roles of PPAR $ß / d$ in keratinocyte response to inflammation,” Genes & Development, vol. 15, no. 24, pp. 3263–3277, 2001.
View at: Publisher Site | Google Scholar
N. S. Tan, L. Michalik, N. Di-Poi, B. Desvergne, and W. Wahli, “Critical roles of the nuclear receptor PPAR $β$ (peroxisome-proliferator-activated receptor $β$ ) in skin wound healing,” Biochemical Society Transactions, vol. 32, no. 1, pp. 97–102, 2004.
View at: Publisher Site | Google Scholar
Y.-X. Wang, C.-L. Zhang, R. T. Yu et al., “Regulation of muscle fiber type and running endurance by PPAR $d$ ,” PLoS Biology, vol. 2, no. 10, p. e294, 2004.
View at: Publisher Site | Google Scholar
G. Icre, W. Wahli, and L. Michalik, “Functions of the peroxisome proliferator-activated receptor (PPAR) $α$ and $β$ in skin homeostasis, epithelial repair, and morphogenesis,” The Journal of Investigative Dermatology Symposium Proceedings, vol. 11, no. 1, pp. 30–35, 2006.
View at: Publisher Site | Google Scholar
L. Michalik and W. Wahli, “Peroxisome proliferator-activated receptors (PPARs) in skin health, repair and disease,” Biochimica et Biophysica Acta, vol. 1771, no. 8, pp. 991–998, 2007.
View at: Google Scholar
A. D. Burdick, D. J. Kim, M. A. Peraza, F. J. Gonzalez, and J. M. Peters, “The role of peroxisome proliferator-activated receptor- $β$ / $δ$ in epithelial cell growth and differentiation,” Cell Signal, vol. 18, no. 1, pp. 9–20, 2006.
View at: Publisher Site | Google Scholar
N. Di-Poi, N. S. Tan, L. Michalik, W. Wahli, and B. Desvergne, “Antiapoptotic role of PPAR $β$ in keratinocytes via transcriptional control of the Akt1 signaling pathway,” Molecular Cell, vol. 10, no. 4, pp. 721–733, 2002.
View at: Publisher Site | Google Scholar
O. Braissant, F. Foufelle, C. Scotto, M. Dauca, and W. Wahli, “Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR- $α$ , - $β$ , and - $γ$ in the adult rat,” Endocrinology, vol. 137, no. 1, pp. 354–366, 1996.
View at: Publisher Site | Google Scholar
Y. X. Wang, C. H. Lee, S. Tiep et al., “Peroxisome-proliferator-activated receptor $d$ activates fat metabolism to prevent obesity,” Cell, vol. 113, no. 2, pp. 159–70, 2003.
View at: Publisher Site | Google Scholar
C. H. Lee, K. Kang, I. R. Mehl et al., “Peroxisome proliferator-activated receptor $d$ promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 7, pp. 2434–2439, 2006.
View at: Publisher Site | Google Scholar
T. Yamada, H. Katagiri, T. Asano et al., “Role of PDK1 in insulin-signaling pathway for glucose metabolism in 3T3-L1 adipocytes,” American Journal of Physiology. Endocrinology and Metabolism, vol. 282, no. 6, pp. E1385–E1394, 2002.
View at: Google Scholar
R. T. Nolte, G. B. Wisely, S. Westin et al., “Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor- $?$ ,” Nature, vol. 395, no. 6698, pp. 137–143, 1998.
View at: Publisher Site | Google Scholar
H. E. Xu, M. H. Lambert, V. G. Montana et al., “Molecular recognition of fatty acids by peroxisome proliferator-activated receptors,” Molecular Cell, vol. 3, no. 3, pp. 397–403, 1999.
View at: Publisher Site | Google Scholar
S. A. Fyffe, M. S. Alphey, L. Buetow et al., “Recombinant human PPAR- $ß$ / $d$ ligand-binding domain is locked in an activated conformation by endogenous fatty acids,” Journal of Molecular Biology, vol. 356, no. 4, pp. 1005–1013, 2006.
View at: Publisher Site | Google Scholar
S. Kersten and W. Wahli, “Peroxisome proliferator activated receptor agonists,” EXS, vol. 89, pp. 141–151, 2000.
View at: Google Scholar
B. M. Forman, J. Chen, and R. M. Evans, “Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors $α$ and $δ$ ,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 9, pp. 4312–4317, 1997.
View at: Publisher Site | Google Scholar
N. Shaw, M. Elholm, and N. Noy, “Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor $β / δ$ ,” Journal of Biological Chemistry, vol. 278, no. 43, pp. 41589–41592, 2003.
View at: Publisher Site | Google Scholar
F. Sussman and A. R. De Lera, “Ligand recognition by RAR and RXR receptors: binding and selectivity,” Journal of Medicinal Chemistry, vol. 48, no. 20, pp. 6212–6219, 2005.
View at: Publisher Site | Google Scholar
P. Chambon, “A decade of molecular biology of retinoic acid receptors,” FASEB Journal, vol. 10, no. 9, pp. 940–954, 1996.
View at: Google Scholar
D. J. Mangelsdorf, “Vitamin A receptors,” Nutrition Reviews, vol. 52, no. 2 part 2, pp. S32–S44, 1994.
View at: Google Scholar
L. J. Donato, J. H. Suh, and N. Noy, “Suppression of mammary carcinoma cell growth by retinoic acid: the cell cycle control gene Btg2 is a direct target for retinoic acid receptor signaling,” Cancer Research, vol. 67, no. 2, pp. 609–615, 2007.
View at: Publisher Site | Google Scholar
C. Rochette-Egly and P. Chambon, “F9 embryocarcinoma cells: a cell autonomous model to study the functional selectivity of RARs and RXRs in retinoid signaling,” Histology and Histopathology, vol. 16, no. 3, pp. 909–922, 2001.
View at: Google Scholar
D. J. Park, A. M. Chumakov, P. T. Vuong et al., “CCAAT/enhancer binding protein epsilon is a potential retinoid target gene in acute promyelocytic leukemia treatment,” The Journal of Clinical Investigation, vol. 103, no. 10, pp. 1399–1408, 1999.
View at: Google Scholar
L. Altucci and H. Gronemeyer, “Nuclear receptors in cell life and death,” Trends in Endocrinology and Metabolism, vol. 12, no. 10, pp. 460–468, 2001.
View at: Publisher Site | Google Scholar
L. J. Donato and N. Noy, “Suppression of mammary carcinoma growth by retinoic acid: proapoptotic genes are targets for retinoic acid receptor and cellular retinoic acid-binding protein II signaling,” Cancer Research, vol. 65, no. 18, pp. 8193–8199, 2005.
View at: Publisher Site | Google Scholar
S. Kitareewan, I. Pitha-Rowe, D. Sekula et al., “UBE1L is a retinoid target that triggers PML/RAR $a$ degradation and apoptosis in acute promyelocytic leukemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 6, pp. 3806–3811, 2002.
View at: Publisher Site | Google Scholar
S. B. Wolbach and P. R. Howe, “Nutrition Classics,” The Journal of Experimental Medicine, vol. 42, pp. 753–777, 1925.
View at: Publisher Site | Google Scholar
S. B. Wolbach and P. R. Howe, “Tissue changes following deprivation of fat-soluble A vitamin,” Nutrition Reviews, vol. 36, no. 1, pp. 16–19, 1978.
View at: Google Scholar
B. Chapellier, M. Mark, N. Messaddeq et al., “Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled,” EMBO Journal, vol. 21, no. 13, pp. 3402–3413, 2002.
View at: Publisher Site | Google Scholar
Q. Le, M. I. Dawson, D. R. Soprano, and K. J. Soprano, “Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids,” Oncogene, vol. 19, no. 11, pp. 1457–1465, 2000.
View at: Publisher Site | Google Scholar
S. Wu, A. Donigan, C. D. Platsoucas, W. Jung, D. R. Soprano, and K. J. Soprano, “All-trans-retinoic acid blocks cell cycle progression of human ovarian adenocarcinoma cells at late G1,” Experimental Cell Research, vol. 232, no. 2, pp. 277–286, 1997.
View at: Publisher Site | Google Scholar
S. Wu, D. Zhang, A. Donigan, M. I. Dawson, D. R. Soprano, and K. J. Soprano, “Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth,” Journal of Cellular Biochemistry, vol. 68, no. 3, pp. 378–388, 1998.
View at: Publisher Site | Google Scholar
A. K. Verma, E. A. Conrad, and R. K. Boutwell, “Differential effect of retinoic acid and 7,8-benzoflavone on the induction of mouse skin tumors by the complete carcinogenesis process and by the initiation-promotion regimen,” Cancer Research, vol. 42, no. 9, pp. 3519–3525, 1982.
View at: Google Scholar
N.-S. Tan, N. S. Shaw, N. Vinckenbosch et al., “Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription,” Molecular and Cellular Biology, vol. 22, no. 14, pp. 5114–5127, 2002.
View at: Publisher Site | Google Scholar
M. Schmuth, C. M. Haqq, W. J. Cairns et al., “Peroxisome proliferator-activated receptor (PPAR)- $ß / d$ stimulates differentiation and lipid accumulation in keratinocytes,” Journal of Investigative Dermatology, vol. 122, no. 4, pp. 971–983, 2004.
View at: Publisher Site | Google Scholar
S. Kersten, S. Mandard, N. S. Tan et al., “Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene,” Journal of Biological Chemistry, vol. 275, no. 37, pp. 28488–28493, 2000.
View at: Publisher Site | Google Scholar
T. T. Schug, D. C. Berry, N. S. Shaw, S. N. Travis, and N. Noy, “Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors,” Cell, vol. 129, no. 4, pp. 723–733, 2007.
View at: Publisher Site | Google Scholar
A. S. Budhu, R. Gillilan, and N. Noy, “Localization of the RAR interaction domain of cellular retinoic acid binding protein-II,” Journal of Molecular Biology, vol. 305, no. 4, pp. 939–949, 2001.
View at: Publisher Site | Google Scholar
A. S. Budhu and N. Noy, “Direct channeling of retinoic acid between cellular retinoic acid-binding protein II and retinoic acid receptor sensitizes mammary carcinoma cells to retinoic acid-induced growth arrest,” Molecular and Cellular Biology, vol. 22, no. 8, pp. 2632–2641, 2002.
View at: Publisher Site | Google Scholar
D. Dong, S. E. Ruuska, D. J. Levinthal, and N. Noy, “Distinct roles for cellular retinoic acid-binding proteins I and II in regulating signaling by retinoic acid,” Journal of Biological Chemistry, vol. 274, no. 34, pp. 23695–23698, 1999.
View at: Publisher Site | Google Scholar
R. J. Sessler and N. Noy, “A ligand-activated nuclear localization signal in cellular retinoic acid binding protein-II,” Molecular Cell, vol. 18, no. 3, pp. 343–353, 2005.
View at: Publisher Site | Google Scholar
D. Manor, E. N. Shmidt, A. Budhu et al., “Mammary carcinoma suppression by cellular retinoic acid binding protein-II,” Cancer Research, vol. 63, no. 15, pp. 4426–4433, 2003.
View at: Google Scholar
L.H. Gutiérrez-González, C. Ludwig, C. Hohoff et al., “Solution structure and backbone dynamics of human epidermal-type fatty acid-binding protein (E-FABP),” Biochemical Journal, vol. 364, no. 3, pp. 725–737, 2002.
View at: Publisher Site | Google Scholar
A. W. Norris and A. A. Spector, “Very long chain n-3 and n-6 polyunsaturated fatty acids bind strongly to liver fatty acid-binding protein,” Journal of Lipid Research, vol. 43, no. 4, pp. 646–653, 2002.
View at: Google Scholar

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Copyright © 2007 Daniel C. Berry and Noa Noy. 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.

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