Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2009 (2009), Article ID 925309, 9 pages
http://dx.doi.org/10.1155/2009/925309
Review Article

Cross-Talk between PPARs and the Partners of RXR: A Molecular Perspective

1Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2M9
2Discipline of Molecular and Cellular Biology, J. Douglas Crashley Myelodysplastic Syndrome Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, T2-058, Toronto, ON, Canada M4N 3M5
3Department of Medical Oncology, Crashley Myelodysplastic Syndromes Research Laboratory, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada M4N 3M5
4Department of Medicine, University of Toronto, Toronto, ON, Canada M4G 2C4

Received 2 September 2009; Accepted 7 September 2009

Academic Editor: Xing-Ming Shi

Copyright © 2009 Lap Shu Alan Chan and Richard A. Wells. 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.

Linked References

  1. I. Issemann and S. Green, “Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators,” Nature, vol. 347, no. 6294, pp. 645–650, 1990. View at Publisher · View at Google Scholar · View at Scopus
  2. M. Okuno, E. Arimoto, Y. Ikenobu, T. Nishihara, and M. Imagawa, “Dual DNA-binding specificity of peroxisome-proliferator-activated receptor γ controlled by heterodimer formation with retinoid X receptor γ,” Biochemical Journal, vol. 353, no. 2, pp. 193–198, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Y. Tsai and M.-J. Tsai, “Chick ovalbumin upstream promoter-transcription factors (COUP-TFs): coming of age,” Endocrine Reviews, vol. 18, no. 2, pp. 229–240, 1997. View at Publisher · View at Google Scholar · View at Scopus
  4. 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 · View at Google Scholar · View at Scopus
  5. V. Giguere, “Orphan nuclear receptors: from gene to function,” Endocrine Reviews, vol. 20, no. 5, pp. 689–725, 1999. View at Google Scholar · View at Scopus
  6. A. A. Bogan, Q. Dallas-Yang, M. D. Ruse Jr. et al., “Analysis of protein dimerization and ligand binding of orphan receptor HNF4a,” Journal of Molecular Biology, vol. 302, no. 4, pp. 831–851, 2000. View at Publisher · View at Google Scholar · View at Scopus
  7. C.-H. Lee, C. Chinpaisal, and L.-N. Wei, “A novel nuclear receptor heterodimerization pathway mediated by orphan receptors TR2 and TR4,” Journal of Biological Chemistry, vol. 273, no. 39, pp. 25209–25215, 1998. View at Publisher · View at Google Scholar · View at Scopus
  8. R. H. Zetterstrom, L. Solomin, T. Mitsiadis, L. Olson, and T. Perlmann, “Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1,” Molecular Endocrinology, vol. 10, no. 12, pp. 1656–1666, 1996. View at Publisher · View at Google Scholar · View at Scopus
  9. P. L. Hallenbeck, M. S. Marks, R. E. Lippoldt, K. Ozato, and V. M. Nikodem, “Heterodimerization of thyroid hormone (TH) receptor with H-2RIIBP (RXRβ) enhances DNA binding and TH-dependent transcriptional activation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 12, pp. 5572–5576, 1992. View at Publisher · View at Google Scholar · View at Scopus
  10. W. Seol, H.-S. Choi, and D. D. Moore, “Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors,” Molecular Endocrinology, vol. 9, no. 1, pp. 72–85, 1995. View at Google Scholar · View at Scopus
  11. M. Nishimura, S. Naito, and T. Yokoi, “Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies,” Drug Metabolism and Pharmacokinetics, vol. 19, no. 2, pp. 135–149, 2004. View at Google Scholar · View at Scopus
  12. P. Dolle, “Developmental expression of retinoic acid receptors (RARs),” Nuclear Receptor Signaling, vol. 7, article e006, 2009. View at Google Scholar · View at Scopus
  13. L. Michalik, B. Desvergne, C. Dreyer, M. Gavillet, R. N. Laurini, and W. Wahli, “PPAR expression and function during vertebrate development,” International Journal of Developmental Biology, vol. 46, no. 1, pp. 105–114, 2002. View at Google Scholar · View at Scopus
  14. D. Forrest, M. Sjoberg, and B. Vennstrom, “Contrasting developmental and tissue-specific expression of α and β thyroid hormone receptor genes,” EMBO Journal, vol. 9, no. 5, pp. 1519–1528, 1990. View at Google Scholar · View at Scopus
  15. D. K. Panda, S. A. Kawas, M. F. Seldin, G. N. Hendy, and D. Goltzman, “25-Hydroxyvitamin D 1α-hydroxylase: structure of the mouse gene, chromosomal assignment, and developmental expression,” Journal of Bone and Mineral Research, vol. 16, no. 1, pp. 46–56, 2001. View at Google Scholar · View at Scopus
  16. L. J. Jonk, M. E. de Jonge, C. E. Pals et al., “Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors,” Mechanisms of Development, vol. 47, no. 1, pp. 81–97, 1994. View at Publisher · View at Google Scholar · View at Scopus
  17. N. J. McKenna, A. J. Cooney, F. J. Demayo et al., “Minireview: evolution of NURSA, the nuclear receptor signaling atlas,” Molecular Endocrinology, vol. 23, no. 6, pp. 740–746, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. K. Umesono, K. K. Murakami, C. C. Thompson, and R. M. Evans, “Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors,” Cell, vol. 65, no. 7, pp. 1255–1266, 1991. View at Google Scholar · View at Scopus
  19. F. Rastinejad, “Retinoid X receptor and its partners in the nuclear receptor family,” Current Opinion in Structural Biology, vol. 11, no. 1, pp. 33–38, 2001. View at Publisher · View at Google Scholar · View at Scopus
  20. B. M. Forman and R. M. Evans, “Nuclear hormone receptors activate direct, inverted, and everted repeats,” Annals of the New York Academy of Sciences, vol. 761, pp. 29–37, 1995. View at Publisher · View at Google Scholar · View at Scopus
  21. F. Rastinejad, T. Perlmann, R. M. Evans, and P. B. Sigler, “Structural determinants of nuclear receptor assembly on DNA direct repeats,” Nature, vol. 375, no. 6528, pp. 203–211, 1995. View at Google Scholar · View at Scopus
  22. Q. Zhao, S. A. Chasse, S. Devarakonda, M. L. Sierk, B. Ahvazi, and F. Rastinejad, “Structural basis of RXR-DNA interactions,” Journal of Molecular Biology, vol. 296, no. 2, pp. 509–520, 2000. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Rastinejad, T. Wagner, Q. Zhao, and S. Khorasanizadeh, “Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1,” EMBO Journal, vol. 19, no. 5, pp. 1045–1054, 2000. View at Google Scholar · View at Scopus
  24. J. D. Tugwood, I. Issemann, R. G. Anderson, K. R. Bundell, W. L. McPheat, and S. Green, “The mouse peroxisome proliferator activated receptor recognizes a response element in the 5 flanking sequence of the rat acyl CoA oxidase gene,” EMBO Journal, vol. 11, no. 2, pp. 433–439, 1992. View at Google Scholar · View at Scopus
  25. V. Chandra, P. Huang, Y. Hamuro et al., “Structure of the intact PPAR-?-RXR-a nuclear receptor complex on DNA,” Nature, vol. 456, no. 7220, pp. 350–356, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Mader, P. Leroy, J.-Y. Chen, and P. Chambon, “Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors,” Journal of Biological Chemistry, vol. 268, no. 1, pp. 591–600, 1993. View at Google Scholar · View at Scopus
  27. B. M. Forman, J. Casanova, B. M. Raaka, J. Ghysdael, and H. H. Samuels, “Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptors and related factors bind to DNA response elements as monomers, homodimers, or heterodimers,” Molecular Endocrinology, vol. 6, no. 3, pp. 429–442, 1992. View at Publisher · View at Google Scholar · View at Scopus
  28. A. M. Naar, J.-M. Boutin, S. M. Lipkin et al., “The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors,” Cell, vol. 65, no. 7, pp. 1267–1279, 1991. View at Google Scholar · View at Scopus
  29. R. Kurokawa, M. Soderstrom, A. Horlein et al., “Polarity-specific activities of retinoic acid receptors determined by a co-repressor,” Nature, vol. 377, no. 6548, pp. 451–454, 1995. View at Google Scholar · View at Scopus
  30. R. Kurokawa, J. DiRenzo, and M. Boehm, “Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding,” Nature, vol. 371, no. 6497, pp. 528–531, 1994. View at Publisher · View at Google Scholar · View at Scopus
  31. S. A. Kliewer, K. Umesono, D. J. Noonan, R. A. Heyman, and R. M. Evans, “Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors,” Nature, vol. 358, no. 6389, pp. 771–774, 1992. View at Publisher · View at Google Scholar · View at Scopus
  32. D. J. Mangelsdorf, K. Umesono, S. A. Kliewer, U. Borgmeyer, E. S. Ong, and R. M. Evans, “A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR,” Cell, vol. 66, no. 3, pp. 555–561, 1991. View at Google Scholar · View at Scopus
  33. H. Nakshatri and P. Bhat-Nakshatri, “Multiple parameters determine the specificity of transcriptional response by nuclear receptors HNF-4, ARP-1, PPAR, RAR and RXR through common response elements,” Nucleic Acids Research, vol. 26, no. 10, pp. 2491–2499, 1998. View at Publisher · View at Google Scholar · View at Scopus
  34. A. IJpenberg, E. Jeannin, W. Wahli, and B. Desvergne, “Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element,” Journal of Biological Chemistry, vol. 272, no. 32, pp. 20108–20117, 1997. View at Publisher · View at Google Scholar · View at Scopus
  35. V. Vivat-Hannah, W. Bourguet, M. Gottardis, and H. Gronemeyer, “Separation of retinoid X receptor homo- and heterodimerization functions,” Molecular and Cellular Biology, vol. 23, no. 21, pp. 7678–7688, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. W. Bourguet, M. Ruff, P. Chambon, H. Gronemeyer, and D. Moras, “Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-α,” Nature, vol. 375, no. 6530, pp. 377–382, 1995. View at Google Scholar · View at Scopus
  37. W. Bourguet, P. Germain, and H. Gronemeyer, “Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications,” Trends in Pharmacological Sciences, vol. 21, no. 10, pp. 381–388, 2000. View at Publisher · View at Google Scholar · View at Scopus
  38. 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 · View at Google Scholar · View at Scopus
  39. W. Bourguet, V. Vivat, J.-M. Wurtz, P. Chambon, H. Gronemeyer, and D. Moras, “Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains,” Molecular Cell, vol. 5, no. 2, pp. 289–298, 2000. View at Google Scholar · View at Scopus
  40. V. Pogenberg, J.-F. Guichoul, V. Vivat-Hannah et al., “Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies,” Journal of Biological Chemistry, vol. 280, no. 2, pp. 1625–1633, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. K. Suino, L. Peng, R. Reynolds et al., “The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization,” Molecular Cell, vol. 16, no. 6, pp. 893–905, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. R. X. Xu, M. H. Lambert, B. B. Wisely et al., “A structural basis for constitutive activity in the human CAR/RXRa heterodimer,” Molecular Cell, vol. 16, no. 6, pp. 919–928, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. M. C. Jaye, J. A. Krawiec, N. Campobasso et al., “Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure,” Journal of Medicinal Chemistry, vol. 48, no. 17, pp. 5419–5422, 2005. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Svensson, T. Östberg, M. Jacobsson et al., “Crystal structure of the heterodimeric complex of LXRa and RXRß ligand-binding domains in a fully agonistic conformation,” EMBO Journal, vol. 22, no. 18, pp. 4625–4633, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. R. T. Gampe Jr., V. G. Montana, M. H. Lambert et al., “Asymmetry in the PPAR?/RXRa crystal structure reveals the molecular basis of heterodimerization among nuclear receptors,” Molecular Cell, vol. 5, pp. 545–555, 2000. View at Google Scholar
  46. H. E. Xu, M. H. Lambert, V. G. Montana et al., “Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 24, pp. 13919–13924, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. C. D. Haffner, J. M. Lenhard, A. B. Miller et al., “Structure-based design of potent retinoid X receptor a agonists,” Journal of Medicinal Chemistry, vol. 47, no. 8, pp. 2010–2029, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. Z.-P. Chen, J. Iyer, W. Bourguet et al., “Ligand- and DNA-induced dissociation of RXR tetramers,” Journal of Molecular Biology, vol. 275, no. 1, pp. 55–65, 1998. View at Publisher · View at Google Scholar · View at Scopus
  49. D. Dong and N. Noy, “Heterodimer formation by retinoid X receptor: regulation by ligands and by the receptor's self-association properties,” Biochemistry, vol. 37, no. 30, pp. 10691–10700, 1998. View at Publisher · View at Google Scholar · View at Scopus
  50. T. Ide, H. Shimano, T. Yoshikawa et al., “Cross-talk between peroxisome proliferator-activated receptor (PPAR) a and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling,” Molecular Endocrinology, vol. 17, no. 7, pp. 1255–1267, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. T. Yoshikawa, T. Ide, H. Shimano et al., “Cross-talk between peroxisome proliferator-activated receptor (PPAR) a and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARS suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling,” Molecular Endocrinology, vol. 17, no. 7, pp. 1240–1254, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. K. S. Miyata, B. Zhang, S. L. Marcus, J. P. Capone, and R. A. Rachubinski, “Chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds to a peroxisome proliferator-responsive element and antagonizes peroxisome proliferator-mediated signaling,” Journal of Biological Chemistry, vol. 268, no. 26, pp. 19169–19172, 1993. View at Google Scholar · View at Scopus
  53. K. Hashimoto, R. N. Cohen, M. Yamada et al., “Cross-talk between thyroid hormone receptor and liver X receptor regulatory pathways is revealed in a thyroid hormone resistance mouse model,” Journal of Biological Chemistry, vol. 281, no. 1, pp. 295–302, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. P. D. Thompson, J.-C. Hsieh, G. K. Whitfield et al., “Vitamin D receptor displays DNA binding and transactivation as a heterodimer with the retinoid X receptor, but not with the thyroid hormone receptor,” Journal of Cellular Biochemistry, vol. 75, no. 3, pp. 462–480, 1999. View at Publisher · View at Google Scholar · View at Scopus
  55. D. J. Waxman, “P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR,” Archives of Biochemistry and Biophysics, vol. 369, no. 1, pp. 11–23, 1999. View at Publisher · View at Google Scholar · View at Scopus
  56. X.-K. Zhang, G. Salbert, M.-O. Lee, and M. Pfahl, “Mutations that alter ligand-induced switches and dimerization activities in the retinoid X receptor,” Molecular and Cellular Biology, vol. 14, no. 6, pp. 4311–4323, 1994. View at Google Scholar · View at Scopus
  57. T. Perlmann, K. Umesono, P. N. Rangarajan, B. M. Forman, and R. M. Evans, “Two distinct dimerization interfaces differentially modulate target gene specificity of nuclear hormone receptors,” Molecular Endocrinology, vol. 10, no. 8, pp. 958–966, 1996. View at Publisher · View at Google Scholar · View at Scopus
  58. S.-K. Lee, B. Lee, and J. W. Lee, “Mutations in retinoid X receptor that impair heterodimerization with specific nuclear hormone receptor,” Journal of Biological Chemistry, vol. 275, no. 43, pp. 33522–33526, 2000. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Nakajima, J.-C. Hsieh, and P. N. MacDonald, “The C-terminal region of the vitamin D receptor is essential to form a complex with a receptor auxiliary factor required for high affinity binding to the vitamin D-responsive element,” Molecular Endocrinology, vol. 8, no. 2, pp. 159–172, 1994. View at Publisher · View at Google Scholar · View at Scopus
  60. H. M. Sucov, E. Dyson, C. L. Gumeringer, J. Price, K. R. Chien, and R. M. Evans, “RXRα mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis,” Genes and Development, vol. 8, no. 9, pp. 1007–1018, 1994. View at Google Scholar · View at Scopus
  61. J. Chen, S. W. Kubalak, and K. R. Chien, “Ventricular muscle-restricted targeting of the RXRα gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis,” Development, vol. 125, no. 10, pp. 1943–1949, 1998. View at Google Scholar · View at Scopus
  62. Y. Wu, X. Zhang, F. Bardag-Gorce et al., “Retinoid X receptor a regulates glutathione homeostasis and xenobiotic detoxification processes in mouse liver,” Molecular Pharmacology, vol. 65, no. 3, pp. 550–557, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. T. Imai, M. Jiang, P. Kastner, P. Chambon, and D. Metzger, “Selective ablation of retinoid X receptor α in hepatocytes impairs their lifespan and regenerative capacity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 8, pp. 4581–4586, 2001. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Li, A. K. Indra, X. Warot et al., “Skin abnormalities generated by temporally controlled RXRa mutations in mouse epidermis,” Nature, vol. 407, no. 6804, pp. 633–636, 2000. View at Publisher · View at Google Scholar · View at Scopus
  65. 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 · View at Google Scholar · View at Scopus
  66. J. Huang, W. C. Powell, A. C. Khodavirdi et al., “Prostatic intraepithelial neoplasia in mice with conditional disruption of the retinoid X receptor a allele in the prostate epithelium,” Cancer Research, vol. 62, no. 16, pp. 4812–4819, 2002. View at Google Scholar · View at Scopus
  67. Y. Barak, M. C. Nelson, E. S. Ong et al., “PPAR? is required for placental, cardiac, and adipose tissue development,” Molecular Cell, vol. 4, no. 4, pp. 585–595, 1999. View at Publisher · View at Google Scholar · View at Scopus
  68. S. M. Rangwala and M. A. Lazar, “Peroxisome proliferator-activated receptor γ in diabetes and metabolism,” Trends in Pharmacological Sciences, vol. 25, no. 6, pp. 331–336, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. N. Kubota, Y. Terauchi, H. Miki et al., “PPAR? mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance,” Molecular Cell, vol. 4, no. 4, pp. 597–609, 1999. View at Publisher · View at Google Scholar · View at Scopus
  70. P. Chambon, “The retinoid signaling pathway: molecular and genetic analyses,” Seminars in Cell Biology, vol. 5, no. 2, pp. 115–125, 1994. View at Google Scholar · View at Scopus
  71. M. Mark, N. B. Ghyselinck, O. Wendling et al., “A genetic dissection of the retinoid signalling pathway in the mouse,” Proceedings of the Nutrition Society, vol. 58, no. 2, pp. 609–613, 1999. View at Google Scholar
  72. E. Hondares, O. Mora, P. Yubero et al., “Thiazolidinediones and rexinoids induce peroxisome proliferator-activated receptor-coactivator (PGC)-1a gene transcription: an autoregulatory loop controls PGC-1a expression in adipocytes via peroxisome proliferator-activated receptor-? coactivation,” Endocrinology, vol. 147, no. 6, pp. 2829–2838, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. T. Teruel, J. C. Clapham, and S. A. Smith, “PPARγ activation by Wy 14643 induces transactivation of the Rat UCP-1 promoter without increasing UCP-1 mRNA levels and attenuates PPARγ-mediated increases in UCP-1 mRNA levels induced by rosiglitazone in fetal rat brown adipocytes,” Biochemical and Biophysical Research Communications, vol. 264, no. 2, pp. 311–315, 1999. View at Publisher · View at Google Scholar · View at Scopus
  74. J. Berger, M. D. Leibowitz, T. W. Doebber et al., “Novel peroxisome proliferator-activated receptor (PPAR) ? and PPARd ligands produce distinct biological effects,” Journal of Biological Chemistry, vol. 274, no. 10, pp. 6718–6725, 1999. View at Publisher · View at Google Scholar · View at Scopus
  75. J. E. Cobb, S. G. Blanchard, E. G. Boswell et al., “N-(2-benzoylphenyl)-L-tyrosine PPAR? agonists. 3. Structure-activity relationship and optimization of the N-aryl substituent,” Journal of Medicinal Chemistry, vol. 41, no. 25, pp. 5055–5069, 1998. View at Publisher · View at Google Scholar · View at Scopus
  76. H. M. Wright, C. B. Clish, T. Mikami et al., “A synthetic antagonist for the peroxisome proliferator-activated receptor ? inhibits adipocyte differentiation,” Journal of Biological Chemistry, vol. 275, no. 3, pp. 1873–1877, 2000. View at Publisher · View at Google Scholar · View at Scopus
  77. R. Mukherjee, P. A. Hoener, L. Jow et al., “A selective peroxisome proliferator-activated receptor-? (PPAR?) modulator blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes,” Molecular Endocrinology, vol. 14, no. 9, pp. 1425–1433, 2000. View at Google Scholar · View at Scopus
  78. T.-C. He, T. A. Chan, B. Vogelstein, and K. W. Kinzler, “PPARδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs,” Cell, vol. 99, no. 3, pp. 335–345, 1999. View at Publisher · View at Google Scholar · View at Scopus
  79. C. L. Chaffer, D. M. Thomas, E. W. Thompson, and E. D. Williams, “PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma,” BMC Cancer, vol. 6, article 53, 2006. View at Google Scholar
  80. C.-C. Yang, C.-Y. Ku, S. Wei et al., “Peroxisome proliferator-activated receptor ?-independent repression of prostate-specific antigen expression by thiazolidinediones in prostate cancer cells,” Molecular Pharmacology, vol. 69, no. 5, pp. 1564–1570, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Aggarwal, S.-W. Kim, K. Cheon, F. H. Tabassam, J.-H. Yoon, and J. S. Koo, “Nonclassical action of retinoic acid on the activation of the cAMP response element-binding protein in normal human bronchial epithelial cells,” Molecular Biology of the Cell, vol. 17, no. 2, pp. 566–575, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. L. S. Chan and R. A. Wells, “Manipulation of reciprocal salt bridges at the heterodimerization interface alters the dimerization properties of mouse RXRα and PPARγ1,” Biochemical and Biophysical Research Communications, vol. 358, no. 4, pp. 1080–1085, 2007. View at Publisher · View at Google Scholar · View at Scopus