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The FASEB Journal, Vol 10, 940-954, Copyright © 1996 by The Federation of American Societies for Experimental Biology

REVIEWS

A decade of molecular biology of retinoic acid receptors

P Chambon
Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERUM/ULP, College de France, Strasbourg, France.

Retinoids play an important role in development, differentiation, and homeostasis. The discovery of retinoid receptors belonging to the superfamily of nuclear ligand-activated transcriptional regulators has revolutionized our molecular understanding as to how these structurally simple molecules exert their pleiotropic effects. Diversity in the control of gene expression by retinoid signals is generated through complexity at different levels of the signaling pathway. A major source of diversity originates from the existence of two families of retinoid acid (RA) receptors (R), the RAR isotypes (alpha, beta, and gamma) and the three RXR isotypes (alpha, beta, and gamma), and their numerous isoforms, which bind as RXR/RAR heterodimers to the polymorphic cis- acting response elements of RA target genes. The possibility of cross- modulation (cross-talk) with cell-surface receptors signaling pathways, as well as the finding that RARs and RXRs interact with multiple putative coactivators and/or corepressors, generates additional levels of complexity for the array of combinatorial effects that underlie the pleiotropic effects of retinoids. This review focuses on recent developments, particularly in the area of structure-function relationships.


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K. Ohnuma-Ishikawa, T. Morio, T. Yamada, Y. Sugawara, M. Ono, M. Nagasawa, A. Yasuda, C. Morimoto, K. Ohnuma, N. H. Dang, et al.
Knockdown of XAB2 Enhances All-Trans Retinoic Acid-Induced Cellular Differentiation in All-Trans Retinoic Acid-Sensitive and -Resistant Cancer Cells
Cancer Res., February 1, 2007; 67(3): 1019 - 1029.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. R. Moise, M. Golczak, Y. Imanishi, and K. Palczewski
Topology and Membrane Association of Lecithin: Retinol Acyltransferase
J. Biol. Chem., January 19, 2007; 282(3): 2081 - 2090.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
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 Res., January 15, 2007; 67(2): 609 - 615.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Isken, J. Holzschuh, J. M. Lampert, L. Fischer, V. Oberhauser, K. Palczewski, and J. von Lintig
Sequestration of Retinyl Esters Is Essential for Retinoid Signaling in the Zebrafish Embryo
J. Biol. Chem., January 12, 2007; 282(2): 1144 - 1151.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
O. Ziouzenkova, G. Orasanu, G. Sukhova, E. Lau, J. P. Berger, G. Tang, N. I. Krinsky, G. G. Dolnikowski, and J. Plutzky
Asymmetric Cleavage of {beta}-Carotene Yields a Transcriptional Repressor of Retinoid X Receptor and Peroxisome Proliferator-Activated Receptor Responses
Mol. Endocrinol., January 1, 2007; 21(1): 77 - 88.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
S. Folkertsma, P. I. van Noort, A. de Heer, P. Carati, R. Brandt, A. Visser, G. Vriend, and J. de Vlieg
The Use of in Vitro Peptide Binding Profiles and in Silico Ligand-Receptor Interaction Profiles to Describe Ligand-Induced Conformations of the Retinoid X Receptor {alpha} Ligand-Binding Domain
Mol. Endocrinol., January 1, 2007; 21(1): 30 - 48.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
X.-H. Tang, M.-J. Suh, R. Li, and L. J. Gudas
Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid
J. Lipid Res., January 1, 2007; 48(1): 165 - 176.
[Abstract] [Full Text] [PDF]

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 Molecular Cancer TherapeuticsHome page
Y. Kato, B. C. Salumbides, X.-F. Wang, D. Z. Qian, S. Williams, Y. Wei, T. B. Sanni, P. Atadja, and R. Pili
Antitumor effect of the histone deacetylase inhibitor LAQ824 in combination with 13-cis-retinoic acid in human malignant melanoma
Mol. Cancer Ther., January 1, 2007; 6(1): 70 - 81.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
C. W. Xiao, J. Mei, W. Huang, C. Wood, M. R. L'Abbe, G. S. Gilani, G. M. Cooke, and I. H. Curran
Dietary Soy Protein Isolate Modifies Hepatic Retinoic Acid Receptor-{beta} Proteins and Inhibits Their DNA Binding Activity in Rats
J. Nutr., January 1, 2007; 137(1): 1 - 6.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
M. D. Williams, N. Chakravarti, M. S. Kies, S.-I. Maruya, J. N. Myers, J. C. Haviland, R. S. Weber, R. Lotan, and A. K. El-Naggar
Implications of Methylation Patterns of Cancer Genes in Salivary Gland Tumors
Clin. Cancer Res., December 15, 2006; 12(24): 7353 - 7358.
[Abstract] [Full Text] [PDF]

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 Pharmacol. Rev.Home page
P. Germain, B. Staels, C. Dacquet, M. Spedding, and V. Laudet
Overview of Nomenclature of Nuclear Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 685 - 704.
[Abstract] [Full Text] [PDF]

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 Pharmacol. Rev.Home page
P. Germain, P. Chambon, G. Eichele, R. M. Evans, M. A. Lazar, M. Leid, A. R. De Lera, R. Lotan, D. J. Mangelsdorf, and H. Gronemeyer
International Union of Pharmacology. LX. Retinoic Acid Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 712 - 725.
[Abstract] [Full Text] [PDF]

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 Pharmacol. Rev.Home page
P. Germain, P. Chambon, G. Eichele, R. M. Evans, M. A. Lazar, M. Leid, A. R. De Lera, R. Lotan, D. J. Mangelsdorf, and H. Gronemeyer
International Union of Pharmacology. LXIII. Retinoid X Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 760 - 772.
[Abstract] [Full Text] [PDF]

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 Pharmacol. Rev.Home page
G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al.
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D.-Y. Xuan, X. Li, Z.-H. Deng, H.-L. Zhang, P.-x. Feng, X.-Y. Duan, and Y. Jin
Identification and Characterization of a Novel Gene, Mcpr1, and Its Possible Function in the Proliferation of Embryonic Palatal Mesenchymal Cells
J. Biol. Chem., November 10, 2006; 281(45): 33997 - 34008.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
T. H. Tezel, L. Geng, H. J. Kaplan, and L. V. Del Priore
Retinal Pigment Epithelium Rescues Vascular Endothelium from Retinoic Acid-Induced Apoptosis
Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5075 - 5087.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
Y. Tateishi, R. Sonoo, Y.-i. Sekiya, N. Sunahara, M. Kawano, M. Wayama, R. Hirota, Y.-i. Kawabe, A. Murayama, S. Kato, et al.
Turning Off Estrogen Receptor {beta}-Mediated Transcription Requires Estrogen-Dependent Receptor Proteolysis
Mol. Cell. Biol., November 1, 2006; 26(21): 7966 - 7976.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
G. Bistulfi, S. Pozzi, M. Ren, S. Rossetti, and N. Sacchi
A Repressive Epigenetic Domino Effect Confers Susceptibility to Breast Epithelial Cell Transformation: Implications for Predicting Breast Cancer Risk
Cancer Res., November 1, 2006; 66(21): 10308 - 10314.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
H. Freeman and R.D. Cox
Type-2 diabetes: a cocktail of genetic discovery
Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R202 - R209.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. J. Choi, S. S. Chung, E. J. Rho, H. W. Lee, M. H. Lee, H.-S. Choi, J. H. Seol, S. H. Baek, O. S. Bang, and C. H. Chung
Negative Modulation of RXR{alpha} Transcriptional Activity by Small Ubiquitin-related Modifier (SUMO) Modification and Its Reversal by SUMO-specific Protease SUSP1
J. Biol. Chem., October 13, 2006; 281(41): 30669 - 30677.
[Abstract] [Full Text] [PDF]

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 JEMHome page
I. Szatmari, A. Pap, R. Ruhl, J.-X. Ma, P. A. Illarionov, G. S. Besra, E. Rajnavolgyi, B. Dezso, and L. Nagy
PPAR{gamma} controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells
J. Exp. Med., October 2, 2006; 203(10): 2351 - 2362.
[Abstract] [Full Text] [PDF]

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 J. Leukoc. Biol.Home page
M. Ricote, C. S. Snyder, H.-Y. Leung, J. Chen, K. R. Chien, and C. K. Glass
Normal hematopoiesis after conditional targeting of RXR{alpha} in murine hematopoietic stem/progenitor cells
J. Leukoc. Biol., October 1, 2006; 80(4): 850 - 861.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
J.-g. Wang, L. W. Barsky, E. Davicioni, K. I. Weinberg, T. J. Triche, X.-k. Zhang, and L. Wu
Retinoic acid induces leukemia cell G1 arrest and transition into differentiation by inhibiting cyclin-dependent kinase-activating kinase binding and phosphorylation of PML/RAR{alpha}
FASEB J, October 1, 2006; 20(12): 2142 - 2144.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
A. Maeda, T. Maeda, M. Golczak, Y. Imanishi, P. Leahy, R. Kubota, and K. Palczewski
Effects of Potent Inhibitors of the Retinoid Cycle on Visual Function and Photoreceptor Protection from Light Damage in Mice
Mol. Pharmacol., October 1, 2006; 70(4): 1220 - 1229.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
G. Cimino, F. Lo-Coco, S. Fenu, L. Travaglini, E. Finolezzi, M. Mancini, M. Nanni, A. Careddu, F. Fazi, F. Padula, et al.
Sequential Valproic Acid/All-trans Retinoic Acid Treatment Reprograms Differentiation in Refractory and High-Risk Acute Myeloid Leukemia.
Cancer Res., September 1, 2006; 66(17): 8903 - 8911.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. N. Shelton, I. T. Sandoval, A. Eisinger, S. Chidester, A. Ratnayake, C. M. Ireland, and D. A. Jones
Up-regulation of CYP26A1 in Adenomatous Polyposis Coli-Deficient Vertebrates via a WNT-Dependent Mechanism: Implications for Intestinal Cell Differentiation and Colon Tumor Development.
Cancer Res., August 1, 2006; 66(15): 7571 - 7577.
[Abstract] [Full Text] [PDF]

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 Hum ReprodHome page
A. Rodriguez, C. Diez, S. Ikeda, L.J. Royo, J.N. Caamano, C. Alonso-Montes, F. Goyache, I. Alvarez, N. Facal, and E. Gomez
Retinoids during the in vitro transition from bovine morula to blastocyst
Hum. Reprod., August 1, 2006; 21(8): 2149 - 2157.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
J. P. Chute, G. G. Muramoto, J. Whitesides, M. Colvin, R. Safi, N. J. Chao, and D. P. McDonnell
Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells
PNAS, August 1, 2006; 103(31): 11707 - 11712.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
D. Passeri, A. Marcucci, G. Rizzo, M. Billi, M. Panigada, L. Leonardi, F. Tirone, and F. Grignani
Btg2 enhances retinoic Acid-induced differentiation by modulating histone h4 methylation and acetylation.
Mol. Cell. Biol., July 1, 2006; 26(13): 5023 - 5032.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
X. Gu, F. Xu, W. Song, X. Wang, P. Hu, Y. Yang, X. Gao, and Q. Zhao
A Novel Cytochrome P450, Zebrafish Cyp26D1, Is Involved in Metabolism of All-trans Retinoic Acid
Mol. Endocrinol., July 1, 2006; 20(7): 1661 - 1672.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
H. Tozaki-Saitoh, S. Koizumi, Y. Sato, M. Tsuda, T. Nagao, and K. Inoue
Retinoic Acids Increase P2X2 Receptor Expression through the 5'-Flanking Region of P2rx2 Gene in Rat Phaeochromocytoma PC-12 Cells
Mol. Pharmacol., July 1, 2006; 70(1): 319 - 328.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y.-S. Cho, E.-J. Kim, U.-H. Park, H.-S. Sin, and S.-J. Um
Additional Sex Comb-like 1 (ASXL1), in Cooperation with SRC-1, Acts as a Ligand-dependent Coactivator for Retinoic Acid Receptor
J. Biol. Chem., June 30, 2006; 281(26): 17588 - 17598.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. R. Singh, A. E. Gururaj, R. K. Vadlamudi, and R. Kumar
9-cis-Retinoic Acid Up-regulates Expression of Transcriptional Coregulator PELP1, a Novel Coactivator of the Retinoid X Receptor {alpha} Pathway
J. Biol. Chem., June 2, 2006; 281(22): 15394 - 15404.
[Abstract] [Full Text] [PDF]


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