Synonyms
HZF-3; Immediate-early response protein NOT; NGFI-B/Nur77 beta-type transcription factor homolog; NOT; Nuclear receptor related 1; Nuclear receptor subfamily 4 group A member 2; Nurr1; Orphan nuclear receptor NURR1; RNR1; T-cell nuclear receptor NOT; TINUR; Transcriptionally inducible nuclear receptor; Transcriptionally inducible nuclear receptor related
Historical Background
Orphan nuclear receptor Nurr1, also known as nuclear receptor subfamily 4, group A, member 2 (NR4A2), together with Nur77 (NR4A1) and Nor1 (NR4A3), is a member of the steroid/thyroid hormone nuclear receptor superfamily. Unlike the other nuclear receptors, Nurr1 is an immediate early gene, and its transcription can be induced by various stimuli such as depolarization, cAMP, inflammation, hormones, calcium, and growth factors (Volpicelli et al. 2004). Structurally, Nurr1 lacks a hydrophobic pocket for ligand binding and might function as ligand-independent nuclear receptor (Wang et al. 2016). The...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Barneda-Zahonero B, Servitja JM, Badiola N, Miñano-Molina AJ, Fadó R, Saura CA, et al. Nurr1 protein is required for N-methyl-d-aspartic acid (NMDA) receptor-mediated neuronal survival. J Biol Chem. 2012;287:11351–62. doi:10.1074/jbc.M111.272427.
Cheng HC, Ulane CM, Burke RE. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol. 2010;67:715–25. doi:10.1002/ana.21995.
Decressac M, Kadkhodaei B, Mattsson B, Laguna A, Perlmann T, Björklund A. α-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons. Sci Transl Med. 2012;4:163ra156. doi:10.1126/scitranslmed.3004676.
Decressac M, Volakakis N, Björklund A, Perlmann T. NURR1 in Parkinson disease – from pathogenesis to therapeutic potential. Nat Rev Neurol. 2013;9:629–36. doi:10.1038/nrneurol.2013.209.
Heng X, Jin G, Zhang X, Yang D, Zhu M, Shijun F, et al. Nurr1 regulates Top IIβ and functions in axon genesis of mesencephalic dopaminergic neurons. Mol Neurodegener. 2012;7:4. doi:10.1186/1750-1326-7-4.
Kim CH, Han BS, Moon J, Kim DJ, Shin J, Rajan S, et al. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. Proc Natl Acad Sci. 2015;112:8756–61. doi:10.1073/pnas.1509742112.
Liu H, Wei L, Tao Q, Deng H, Ming M, Xu P, et al. Decreased NURR1 and PITX3 gene expression in Chinese patients with Parkinson’s disease. Eur J Neurol. 2012;19:870–5. doi:10.1111/j.1468-1331.2011.03644.
McCoy JM, Walkenhorst DE, McCauley KS, Elaasar H, Everett JR, Mix KS. Orphan nuclear receptor NR4A2 induces transcription of the immunomodulatory peptide hormone prolactin. J Inflamm (Lond). 2015;12:13. doi:10.1186/s12950-015-0059-2.
Murphy EP, McEvoy A, Conneely OM, Bresnihan B, FitzGerald O. Involvement of the nuclear orphan receptor NURR1 in the regulation of corticotropin-releasing hormone expression and actions in human inflammatory arthritis. Arthritis Rheum. 2001;44:782–93.
Ranhotra HS. The NR4A orphan nuclear receptors: mediators in metabolism and diseases. J Recept Signal Transduct Res. 2015;35:184–8. doi:10.3109/10799893.2014.948555.
Raveney BJ, Oki S, Yamamura T. Nuclear receptor NR4A2 orchestrates Th17 cell-mediated autoimmune inflammation via IL-21 signalling. PLoS One. 2013;8:e56595. doi:10.1371/journal.pone.0056595.
Safe S, Jin UH, Morpurgo B, Abudayyeh A, Singh M, Tjalkens RB. Nuclear receptor 4A (NR4A) family – orphans no more. J Steroid Biochem Mol Biol. 2016;157:48–60.
Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009;137:47–59. doi:10.1016/j.cell.2009.01.038.
Verstraeten A, Theuns J, Van Broeckhoven C. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era. Trends Genet. 2015;31:140–9.
Volpicelli F, Perrone-Capano C, Da Pozzo P, Colucci-D’Amato L, di Porzio U. Modulation of nurr1 gene expression in mesencephalic dopaminergic neurones. J Neurochem. 2004;88:1283–94. Erratum in: J Neurochem. 2004;90:256.
Volpicelli F, Caiazzo M, Greco D, Consales C, Leone L, Perrone-Capano C, et al. Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro. J Neurochem. 2007;102(2):441–53.
Volpicelli F, De Gregorio R, Pulcrano S, Perrone-Capano C, di Porzio U, Bellenchi GC. Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain. PLoS One. 2012;7:e30661. doi:10.1371/journal.pone.0030661.
Wang J, Bi W, Zhao W, Varghese M, Koch RJ, Walker RH, et al. Selective brain penetrable Nurr1 transactivator for treating Parkinson’s disease. Oncotarget. 2016;7:7469–79. doi:10.18632/oncotarget.7191.
Wenzl K, Troppan K, Neumeister P, Deutsch AJ. The nuclear orphan receptor NR4A1 and NR4A3 as tumor suppressors in hematologic neoplasms. Curr Drug Targets. 2015;16:38–46.
Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T. Dopamine neuron agenesis in Nurr1-deficient mice. Science. 1997;276:248–50.
Zheng K, Heydari B, Simon DK. A common NURR1 polymorphism associated with Parkinson disease and diffuse Lewy body disease. Arch Neurol. 2003;60:722–5.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Volpicelli, F., di Porzio, U., Colucci-D’Amato, L. (2018). NR4A2 (Nuclear Receptor Subfamily 4, Group A, Member 2). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101617
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101617
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences