Molecular Endocrinology, Vol 6, 2129-2135, Copyright © 1992 by Endocrine Society

ARTICLES

Identification of a new brain-specific transcription factor, NURR1

SW Law, OM Conneely, FJ DeMayo and BW O'Malley
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.

We have identified and cloned a novel member of the nuclear receptor superfamily. The cDNA was isolated from a mouse brain cDNA library and encodes a protein 598 amino acids in length with a predicted mol wt of 66 kilodaltons. The amino acid sequence of the protein is closely related to an additional family member and immediate early gene product, Nur77, and the novel factor is referred to as Nurr1 (Nur- related factor 1). The relationship between Nurr1 and Nur77 suggests that these proteins constitute an additional subfamily within the nuclear receptor superfamily. Like Nur77, the expression of Nurr1 is induced by membrane depolarization of PC12 cells. However, while Nur77 shows an early transcriptional response to nerve growth factor stimulation, the failure of Nurr1 to respond to this agent suggests a differential selectivity of the two proteins in terms of their transcriptional responses to specific stimuli. Finally, both proteins are differentially expressed during development and in tissues of the adult mouse. Unlike Nur77, Nurr1 appears to be predominantly located in brain tissue, suggesting a primary role for this putative transcription factor in regulation of gene expression in the central nervous system.

This article has been cited by other articles:

				F. M. J. Jacobs, A. J. A. van der Linden, Y. Wang, L. von Oerthel, H. S. Sul, J. P. H. Burbach, and M. P. Smidt Identification of Dlk1, Ptpru and Klhl1 as novel Nurr1 target genes in meso-diencephalic dopamine neurons Development, July 15, 2009; 136(14): 2363 - 2373. [Abstract] [Full Text] [PDF]

				J. Rambaud, J. Desroches, A. Balsalobre, and J. Drouin TIF1{beta}/KAP-1 Is a Coactivator of the Orphan Nuclear Receptor NGFI-B/Nur77 J. Biol. Chem., May 22, 2009; 284(21): 14147 - 14156. [Abstract] [Full Text] [PDF]

				A. G. Smith, N. Luk, R. A. Newton, D. W. Roberts, R. A. Sturm, and G. E. O. Muscat Melanocortin-1 Receptor Signaling Markedly Induces the Expression of the NR4A Nuclear Receptor Subgroup in Melanocytic Cells J. Biol. Chem., May 2, 2008; 283(18): 12564 - 12570. [Abstract] [Full Text] [PDF]

				K. Wang and Y.-J. Y. Wan Nuclear Receptors and Inflammatory Diseases Experimental Biology and Medicine, May 1, 2008; 233(5): 496 - 506. [Abstract] [Full Text] [PDF]

				M. Noguchi, V. Ropars, C. Roumestand, and F. Suizu Proto-oncogene TCL1: more than just a coactivator for Akt FASEB J, August 1, 2007; 21(10): 2273 - 2284. [Abstract] [Full Text] [PDF]

				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]

				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]

				P. Sacchetti, R. Carpentier, P. Segard, C. Olive-Cren, and P. Lefebvre Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1 Nucleic Acids Res., November 14, 2006; 34(19): 5515 - 5527. [Abstract] [Full Text] [PDF]

				W. I. Colon-Cesario, M. M. Martinez-Montemayor, S. Morales, J. Felix, J. Cruz, M. Adorno, L. Pereira, N. Colon, C. S. Maldonado-Vlaar, and S. Pena de Ortiz Knockdown of Nurr1 in the rat hippocampus: Implications to spatial discrimination learning and memory Learn. Mem., November 1, 2006; 13(6): 734 - 744. [Abstract] [Full Text] [PDF]

				P. I. Bonta, C. M. van Tiel, M. Vos, T. W.H. Pols, J. V. van Thienen, V. Ferreira, E. K. Arkenbout, J. Seppen, C. A. Spek, T. van der Poll, et al. Nuclear Receptors Nur77, Nurr1, and NOR-1 Expressed in Atherosclerotic Lesion Macrophages Reduce Lipid Loading and Inflammatory Responses Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2288 - 2288. [Abstract] [Full Text] [PDF]

				M. Hiromura, F. Suizu, M. Narita, K. Kinowaki, and M. Noguchi Identification of Nerve Growth Factor-responsive Element of the TCL1 Promoter as a Novel Negative Regulatory Element J. Biol. Chem., September 22, 2006; 281(38): 27753 - 27764. [Abstract] [Full Text] [PDF]

				A. G. Smith and G. E. O. Muscat Orphan nuclear receptors: therapeutic opportunities in skeletal muscle Am J Physiol Cell Physiol, August 1, 2006; 291(2): C203 - C217. [Abstract] [Full Text] [PDF]

				L. Pei, A. Castrillo, and P. Tontonoz Regulation of Macrophage Inflammatory Gene Expression by the Orphan Nuclear Receptor Nur77 Mol. Endocrinol., April 1, 2006; 20(4): 786 - 794. [Abstract] [Full Text] [PDF]

				H. Zeng, L. Qin, D. Zhao, X. Tan, E. J. Manseau, M. Van Hoang, D. R. Senger, L. F. Brown, J. A. Nagy, and H. F. Dvorak Orphan nuclear receptor TR3/Nur77 regulates VEGF-A-induced angiogenesis through its transcriptional activity J. Exp. Med., March 20, 2006; 203(3): 719 - 729. [Abstract] [Full Text] [PDF]

				L. Pei, A. Castrillo, M. Chen, A. Hoffmann, and P. Tontonoz Induction of NR4A Orphan Nuclear Receptor Expression in Macrophages in Response to Inflammatory Stimuli J. Biol. Chem., August 12, 2005; 280(32): 29256 - 29262. [Abstract] [Full Text] [PDF]

				J. A. Ralph, A. N. McEvoy, D. Kane, B. Bresnihan, O. FitzGerald, and E. P. Murphy Modulation of Orphan Nuclear Receptor NURR1 Expression by Methotrexate in Human Inflammatory Joint Disease Involves Adenosine A2A Receptor-Mediated Responses J. Immunol., July 1, 2005; 175(1): 555 - 565. [Abstract] [Full Text] [PDF]

				S. Chintharlapalli, R. Burghardt, S. Papineni, S. Ramaiah, K. Yoon, and S. Safe Activation of Nur77 by Selected 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes Induces Apoptosis through Nuclear Pathways J. Biol. Chem., July 1, 2005; 280(26): 24903 - 24914. [Abstract] [Full Text] [PDF]

				R. Flaig, H. Greschik, C. Peluso-Iltis, and D. Moras Structural Basis for the Cell-specific Activities of the NGFI-B and the Nurr1 Ligand-binding Domain J. Biol. Chem., May 13, 2005; 280(19): 19250 - 19258. [Abstract] [Full Text] [PDF]

				C. Martens, S. Bilodeau, M. Maira, Y. Gauthier, and J. Drouin Protein-Protein Interactions and Transcriptional Antagonism between the Subfamily of NGFI-B/Nur77 Orphan Nuclear Receptors and Glucocorticoid Receptor Mol. Endocrinol., April 1, 2005; 19(4): 885 - 897. [Abstract] [Full Text] [PDF]

				J. Martinez-Gonzalez and L. Badimon The NR4A subfamily of nuclear receptors: new early genes regulated by growth factors in vascular cells Cardiovasc Res, February 15, 2005; 65(3): 609 - 618. [Abstract] [Full Text] [PDF]

				K. C. Park, K.-H. Song, H. K. Chung, H. Kim, D. W. Kim, J. H. Song, E. S. Hwang, H. S. Jung, S.-H. Park, I. Bae, et al. CR6-Interacting Factor 1 Interacts with Orphan Nuclear Receptor Nur77 and Inhibits Its Transactivation Mol. Endocrinol., January 1, 2005; 19(1): 12 - 24. [Abstract] [Full Text] [PDF]

				X. Cao, W. Liu, F. Lin, H. Li, S. K. Kolluri, B. Lin, Y.-h. Han, M. I. Dawson, and X.-k. Zhang Retinoid X Receptor Regulates Nur77/Thyroid Hormone Receptor 3-Dependent Apoptosis by Modulating Its Nuclear Export and Mitochondrial Targeting Mol. Cell. Biol., November 15, 2004; 24(22): 9705 - 9725. [Abstract] [Full Text] [PDF]

				N. Ke, G. Claassen, D.-H. Yu, A. Albers, W. Fan, P. Tan, M. Grifman, X. Hu, K. DeFife, V. Nguy, et al. Nuclear Hormone Receptor NR4A2 Is Involved in Cell Transformation and Apoptosis Cancer Res., November 15, 2004; 64(22): 8208 - 8212. [Abstract] [Full Text] [PDF]

				T. Ponnio and O. M. Conneely nor-1 Regulates Hippocampal Axon Guidance, Pyramidal Cell Survival, and Seizure Susceptibility Mol. Cell. Biol., October 15, 2004; 24(20): 9070 - 9078. [Abstract] [Full Text] [PDF]

				J. Lammi, J. Huppunen, and P. Aarnisalo Regulation of the Osteopontin Gene by the Orphan Nuclear Receptor NURR1 in Osteoblasts Mol. Endocrinol., June 1, 2004; 18(6): 1546 - 1557. [Abstract] [Full Text] [PDF]

				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 J. Physiol., April 1, 2004; 556(1): 43 - 59. [Abstract] [Full Text] [PDF]

				M. P. Smidt, S. M. Smits, H. Bouwmeester, F. P. T. Hamers, A. J. A. van der Linden, A. J. C. G. M. Hellemons, J. Graw, and J. P. H. Burbach Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3 Development, March 1, 2004; 131(5): 1145 - 1155. [Abstract] [Full Text] [PDF]

				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 J. Biol. Chem., January 16, 2004; 279(3): 2005 - 2011. [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; 17(24): 3036 - 3047. [Abstract] [Full Text] [PDF]

				R. A. DeYoung, J. C. Baker, D. Cado, and A. Winoto The Orphan Steroid Receptor Nur77 Family Member Nor-1 Is Essential for Early Mouse Embryogenesis J. Biol. Chem., November 21, 2003; 278(47): 47104 - 47109. [Abstract] [Full Text] [PDF]

				K. Zheng, B. Heydari, and D. K. Simon A Common NURR1 Polymorphism Associated With Parkinson Disease and Diffuse Lewy Body Disease Arch Neurol, May 1, 2003; 60(5): 722 - 725. [Abstract] [Full Text] [PDF]

				R. Dono Fibroblast growth factors as regulators of central nervous system development and function Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R867 - R881. [Abstract] [Full Text] [PDF]

				M. Maira, C. Martens, E. Batsche, Y. Gauthier, and J. Drouin Dimer-Specific Potentiation of NGFI-B (Nur77) Transcriptional Activity by the Protein Kinase A Pathway and AF-1-Dependent Coactivator Recruitment Mol. Cell. Biol., February 1, 2003; 23(3): 763 - 776. [Abstract] [Full Text]

				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., January 10, 2003; 92(1): 96 - 103. [Abstract] [Full Text] [PDF]

				P. Sacchetti, H. Dwornik, P. Formstecher, C. Rachez, and P. Lefebvre Requirements for Heterodimerization between the Orphan Nuclear Receptor Nurr1 and Retinoid X Receptors J. Biol. Chem., September 13, 2002; 277(38): 35088 - 35096. [Abstract] [Full Text] [PDF]

				P. Aarnisalo, C.-H. Kim, J. W. Lee, and T. Perlmann Defining Requirements for Heterodimerization between the Retinoid X Receptor and the Orphan Nuclear Receptor Nurr1 J. Biol. Chem., September 13, 2002; 277(38): 35118 - 35123. [Abstract] [Full Text] [PDF]

				K. D. S. A. Wansa, J. M. Harris, and G. E. O. Muscat The Activation Function-1 Domain of Nur77/NR4A1 Mediates Trans-activation, Cell Specificity, and Coactivator Recruitment J. Biol. Chem., August 30, 2002; 277(36): 33001 - 33011. [Abstract] [Full Text] [PDF]

				P.-Y. Xu, R. Liang, J. Jankovic, C. Hunter, Y.-X. Zeng, T. Ashizawa, D. Lai, and W.-D. Le Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease Neurology, March 26, 2002; 58(6): 881 - 884. [Abstract] [Full Text] [PDF]

				A. N. McEvoy, E. A. Murphy, T. Ponnio, O. M. Conneely, B. Bresnihan, O. FitzGerald, and E. P. Murphy Activation of Nuclear Orphan Receptor NURR1 Transcription by NF-{kappa}B and Cyclic Adenosine 5'-Monophosphate Response Element-Binding Protein in Rheumatoid Arthritis Synovial Tissue J. Immunol., March 15, 2002; 168(6): 2979 - 2987. [Abstract] [Full Text] [PDF]

				K.-H. Song, J.-I. Park, M.-O. Lee, J. Soh, K. Lee, and H.-S. Choi LH Induces Orphan Nuclear Receptor Nur77 Gene Expression in Testicular Leydig Cells Endocrinology, December 1, 2001; 142(12): 5116 - 5123. [Abstract] [Full Text] [PDF]

				D. S. Castro, E. Hermanson, B. Joseph, A. Wallen, P. Aarnisalo, A. Heller, and T. Perlmann Induction of Cell Cycle Arrest and Morphological Differentiation by Nurr1 and Retinoids in Dopamine MN9D Cells J. Biol. Chem., November 9, 2001; 276(46): 43277 - 43284. [Abstract] [Full Text] [PDF]

				H. Baker, N. Liu, H. S. Chun, S. Saino, R. Berlin, B. Volpe, and J. H. Son Phenotypic Differentiation during Migration of Dopaminergic Progenitor Cells to the Olfactory Bulb J. Neurosci., November 1, 2001; 21(21): 8505 - 8513. [Abstract] [Full Text] [PDF]

				J.-I. Park, H.-J. Park, H.-S. Choi, K. Lee, W.-K. Lee, and S.-Y. Chun Gonadotropin Regulation of NGFI-B Messenger Ribonucleic Acid Expression during Ovarian Follicle Development in the Rat Endocrinology, July 1, 2001; 142(7): 3051 - 3059. [Abstract] [Full Text] [PDF]

				S. Tetradis, O. Bezouglaia, and A. Tsingotjidou Parathyroid Hormone Induces Expression of the Nuclear Orphan Receptor Nurr1 in Bone Cells Endocrinology, February 1, 2001; 142(2): 663 - 670. [Abstract] [Full Text] [PDF]

				P. M. Fernandez, F. Brunel, M. A. Jimenez, J. M. Saez, S. Cereghini, and M. M. Zakin Nuclear Receptors Nor1 and NGFI-B/Nur77 Play Similar, Albeit Distinct, Roles in the Hypothalamo-Pituitary-Adrenal Axis Endocrinology, July 1, 2000; 141(7): 2392 - 2400. [Abstract] [Full Text] [PDF]

				D. S. Castro, M. Arvidsson, M. B. Bolin, and T. Perlmann Activity of the Nurr1 Carboxyl-terminal Domain Depends on Cell Type and Integrity of the Activation Function 2 J. Biol. Chem., December 24, 1999; 274(52): 37483 - 37490. [Abstract] [Full Text] [PDF]

				M. Maira, C. Martens, A. Philips, and J. Drouin Heterodimerization between Members of the Nur Subfamily of Orphan Nuclear Receptors as a Novel Mechanism for Gene Activation Mol. Cell. Biol., November 1, 1999; 19(11): 7549 - 7557. [Abstract] [Full Text] [PDF]

				L.-J. Chew, F. Huang, J.-M. Boutin, and V. Gallo Identification of Nuclear Orphan Receptors as Regulators of Expression of a Neurotransmitter Receptor Gene J. Biol. Chem., October 8, 1999; 274(41): 29366 - 29375. [Abstract] [Full Text] [PDF]

				V. Giguère Orphan Nuclear Receptors: From Gene to Function Endocr. Rev., October 1, 1999; 20(5): 689 - 725. [Abstract] [Full Text]

				M. Werme, P. Thoren, L. Olson, and S. Brene Addiction-Prone Lewis But Not Fischer Rats Develop Compulsive Running that Coincides with Downregulation of Nerve Growth Factor Inducible-B and Neuron-Derived Orphan Receptor 1 J. Neurosci., July 15, 1999; 19(14): 6169 - 6174. [Abstract] [Full Text] [PDF]

				Y. Ueda, S. Bandoh, J. Fujita, M. Sato, Y. Yamaji, and J. Takahara Expression of Nerve Growth Factor-Induced Clone B Subfamily and Pro-opiomelanocortin Gene in Lung Cancer Cell Lines Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1319 - 1325. [Abstract] [Full Text]

				X. Chen, V. Zachar, C. Chang, P. Ebbesen, and X. Liu Differential Expression of Nur77 Family Members in Human T-Lymphotropic Virus Type 1-Infected Cells: Transactivation of the TR3/nur77 Gene by Tax Protein J. Virol., August 1, 1998; 72(8): 6902 - 6906. [Abstract] [Full Text] [PDF]

				J. D. Feldman, L. Vician, M. Crispino, G. Tocco, V. L. Marcheselli, N. G. Bazan, M. Baudry, and H. R. Herschman KID-1, a Protein Kinase Induced by Depolarization in Brain J. Biol. Chem., June 26, 1998; 273(26): 16535 - 16543. [Abstract] [Full Text] [PDF]

				O. Saucedo-Cardenas, J. D. Quintana-Hau, W.-D. Le, M. P. Smidt, J. J. Cox, F. De Mayo, J. P. H. Burbach, and O. M. Conneely Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons PNAS, March 31, 1998; 95(7): 4013 - 4018. [Abstract] [Full Text] [PDF]

				L. F. Michael, M. A. Lazar, and C. R. Mendelson Peroxisome Proliferator-Activated Receptor {gamma}1 Expression Is Induced during Cyclic Adenosine Monophosphate-Stimulated Differentiation of Alveolar Type II Pneumonocytes Endocrinology, September 1, 1997; 138(9): 3695 - 3703. [Abstract] [Full Text] [PDF]

				R. H. Zetterström, L. Solomin, L. Jansson, B. J. Hoffer, L. Olson, and T. Perlmann Dopamine Neuron Agenesis in Nurr1-Deficient Mice Science, April 11, 1997; 276(5310): 248 - 250. [Abstract] [Full Text]

				E. P. Murphy and O. M. Conneely Neuroendocrine Regulation of the Hypothalamic Pituitary Adrenal Axis by the nurr1/nur77 Subfamily of Nuclear Receptors Mol. Endocrinol., January 1, 1997; 11(1): 39 - 47. [Abstract] [Full Text]

				S. Lee, R. Wesselschmidt, G. Linette, O Kanagawa, J. Russell, and J Milbrandt Unimpaired thymic and peripheral T cell death in mice lacking the nuclear receptor NGFI-B (Nur77) Science, July 28, 1995; 269(5223): 532 - 535. [Abstract] [PDF]

				T Perlmann and L Jansson A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes & Dev., April 1, 1995; 9(7): 769 - 782. [Abstract] [PDF]