Molecular Oncology Group, McGill University Health Centre
and Departments of Biochemistry, Medicine, and Oncology, McGill
University, Montréal, Québec, Canada H3A 1A1
I. Introduction
II. Nuclear Receptors: General Concepts
A.Anatomy of nuclear receptors
B. Mechanisms of action
III.Orphan Nuclear Receptors
A. Definition
B. Nomenclature
C.Structural and functional diversity
IV. Novel Hormone ResponseSystems: RXR and Its HeterodimericPartners
A. RXR: rexinoids
B. PPAR: multiple ligands, multiple functions
C. PXR: pregnanes,xenobiotic compounds, and benzoate derivatives
D. CAR (constitutiveandrostane receptor): androstanes and phenobarbital
E. LXR:control of cholesterol metabolism by oxysterols
F. FXR: bileacids receptor
V. Orphans in Search of a Home
A. HNF4: diabetesand possible regulation by acyl-coenzyme A(CoA)
thioesters
B. FTZ-F1: steroidogenesis and sexual development
C. Rev-Erb:singular members of the superfamily
D. ROR: neuron developmentand T cell selection
E. TR2: the testis receptors
F. TLX:forebrain development
G. COUP-TF: neurogenesis, angiogenesis,and heart development
H. ERR: placenta development and controlof lipid metabolism
I. NGFI-B: hypothalamus-pituitary axis(HPA), T cells, and dopaminergic
neurons
J. GCNF: one of akind
K. DAX-1: adrenal development and sex determination
L.SHP: a promiscuous and inhibitory heterodimeric partner
VI.Concluding Remarks
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E. Nsegbe, A. Wallen-Mackenzie, S. Dauger, J.-C. Roux, Y. Shvarev, H. Lagercrantz, T. Perlmann, and E. Herlenius Congenital hypoventilation and impaired hypoxic response in Nurr1 mutant mice
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T. Tokumoto, M. Tokumoto, R. Horiguchi, K. Ishikawa, and Y. Nagahama Diethylstilbestrol induces fish oocyte maturation
PNAS,
March 9, 2004;
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M. H. Bassett, T. Suzuki, H. Sasano, P. C. White, and W. E. Rainey The Orphan Nuclear Receptors NURR1 and NGFIB Regulate Adrenal Aldosterone Production
Mol. Endocrinol.,
February 1, 2004;
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D. Galleguillos, A. Vecchiola, J. A. Fuentealba, V. Ojeda, K. Alvarez, A. Gomez, and M. E. Andres PIAS{gamma} Represses the Transcriptional Activation Induced by the Nuclear Receptor Nurr1
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January 16, 2004;
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Y. Chen, L.-N. Wei, and J. D. Muller Probing protein oligomerization in living cells with fluorescence fluctuation spectroscopy
PNAS,
December 23, 2003;
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[Abstract][Full Text][PDF]
A. Wallen-Mackenzie, A. M. de Urquiza, S. Petersson, F. J. Rodriguez, S. Friling, J. Wagner, P. Ordentlich, J. Lengqvist, R. A. Heyman, E. Arenas, et al. Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells
Genes & Dev.,
December 15, 2003;
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H.-J. Kim, J.-Y. Kim, Y.-Y. Park, and H.-S. Choi Synergistic activation of the human orphan nuclear receptor SHP gene promoter by basic helix-loop-helix protein E2A and orphan nuclear receptor SF-1
Nucleic Acids Res.,
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M. E. Colosimo, S. Tran, and P. Sengupta The Divergent Orphan Nuclear Receptor ODR-7 Regulates Olfactory Neuron Gene Expression via Multiple Mechanisms in Caenorhabditis elegans
Genetics,
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D. Liu, Z. Zhang, W. Gladwell, and C. T. Teng Estrogen Stimulates Estrogen-Related Receptor {alpha} Gene Expression through Conserved Hormone Response Elements
Endocrinology,
November 1, 2003;
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M. Wiens, R. Batel, M. Korzhev, and W. E. G. Muller Retinoid X receptor and retinoic acid response in the marine sponge Suberites domuncula
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M. Gianni, A. Tarrade, E. A. Nigro, E. Garattini, and C. Rochette-Egly The AF-1 and AF-2 Domains of RAR{gamma}2 and RXR{alpha} Cooperate for Triggering the Transactivation and the Degradation of RAR{gamma}2/RXR{alpha} Heterodimers
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S. Suzuki, N. Suzuki, C. Mirtsos, T. Horacek, E. Lye, S.-K. Noh, A. Ho, D. Bouchard, T. W. Mak, and W.-C. Yeh Nur77 as a survival factor in tumor necrosis factor signaling
PNAS,
July 8, 2003;
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S. A. Kliewer The Nuclear Pregnane X Receptor Regulates Xenobiotic Detoxification
J. Nutr.,
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P. Ordentlich, Y. Yan, S. Zhou, and R. A. Heyman Identification of the Antineoplastic Agent 6-Mercaptopurine as an Activator of the Orphan Nuclear Hormone Receptor Nurr1
J. Biol. Chem.,
June 27, 2003;
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S. Catalano, V. Pezzi, A. Chimento, C. Giordano, A. Carpino, M. Young, M. J. McPhaul, and S. Ando Triiodothyronine Decreases the Activity of the Proximal Promoter (PII) of the Aromatase Gene in the Mouse Sertoli Cell Line, TM4
Mol. Endocrinol.,
May 1, 2003;
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H. Mizusaki, K. Kawabe, T. Mukai, E. Ariyoshi, M. Kasahara, H. Yoshioka, A. Swain, and K.-i. Morohashi Dax-1 (Dosage-Sensitive Sex Reversal-Adrenal Hypoplasia Congenita Critical Region on the X Chromosome, Gene 1) Gene Transcription Is Regulated by Wnt4 in the Female Developing Gonad
Mol. Endocrinol.,
April 1, 2003;
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S. N. Schreiber, D. Knutti, K. Brogli, T. Uhlmann, and A. Kralli The Transcriptional Coactivator PGC-1 Regulates the Expression and Activity of the Orphan Nuclear Receptor Estrogen-Related Receptor alpha (ERRalpha )
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K. Otte, H. Kranz, I. Kober, P. Thompson, M. Hoefer, B. Haubold, B. Remmel, H. Voss, C. Kaiser, M. Albers, et al. Identification of Farnesoid X Receptor {beta} as a Novel Mammalian Nuclear Receptor Sensing Lanosterol
Mol. Cell. Biol.,
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J. Martinez-Gonzalez, J. Rius, A. Castello, C. Cases-Langhoff, and L. Badimon Neuron-Derived Orphan Receptor-1 (NOR-1) Modulates Vascular Smooth Muscle Cell Proliferation
Circ. Res.,
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T. Suzuki, M. Kasahara, H. Yoshioka, K.-i. Morohashi, and K. Umesono LXXLL-Related Motifs in Dax-1 Have Target Specificity for the Orphan Nuclear Receptors Ad4BP/SF-1 and LRH-1
Mol. Cell. Biol.,
January 1, 2003;
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E. Raspe, G. Mautino, C. Duval, C. Fontaine, H. Duez, O. Barbier, D. Monte, J. Fruchart, J.-C. Fruchart, and B. Staels Transcriptional Regulation of Human Rev-erbalpha Gene Expression by the Orphan Nuclear Receptor Retinoic Acid-related Orphan Receptor alpha
J. Biol. Chem.,
December 13, 2002;
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L. J. Borgius, K. R. Steffensen, J.-A. Gustafsson, and E. Treuter Glucocorticoid Signaling Is Perturbed by the Atypical Orphan Receptor and Corepressor SHP
J. Biol. Chem.,
December 13, 2002;
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E. Raspe, H. Duez, A. Mansen, C. Fontaine, C. Fievet, J.-C. Fruchart, B. Vennstrom, and B. Staels Identification of Rev-erb{alpha} as a physiological repressor of apoC-III gene transcription
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M. E. Torres-Padilla, F. M. Sladek, and M. C. Weiss Developmentally Regulated N-terminal Variants of the Nuclear Receptor Hepatocyte Nuclear Factor 4alpha Mediate Multiple Interactions through Coactivator and Corepressor-Histone Deacetylase Complexes
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November 15, 2002;
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S. A. Kliewer, B. Goodwin, and T. M. Willson The Nuclear Pregnane X Receptor: A Key Regulator of Xenobiotic Metabolism
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