Nuclear receptor 4A3 explained

The nuclear receptor 4A3 (NR4A3) (nuclear receptor subfamily 4, group A, member 3) also known as neuron-derived orphan receptor 1 (NOR1) is a protein that in humans is encoded by the NR4A3 gene.^[1] NR4A3 is a member of the nuclear receptor family of intracellular transcription factors.

NR4A3 plays a central regulatory role in cell proliferation, differentiation, mitochondrial respiration,^[2] metabolism^{[3] [4]} and apoptosis^[5]

Interactions

NR4A3 has been shown to interact with SIX3.^{[6] [7]}

See also

• NUR nuclear receptor family

Further reading

• Ohkura N, Hijikuro M, Yamamoto A, Miki K . Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells . Biochemical and Biophysical Research Communications . 205 . 3 . 1959–65 . Dec 1994 . 7811288 . 10.1006/bbrc.1994.2900 .
• Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS . Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma . Oncogene . 12 . 2 . 229–35 . Jan 1996 . 8570200 .
• Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M . Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation . Human Molecular Genetics . 4 . 12 . 2219–26 . Dec 1995 . 8634690 . 10.1093/hmg/4.12.2219 .
• Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K . Structure, mapping and expression of a human NOR-1 gene, the third member of the Nur77/NGFI-B family . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1308 . 3 . 205–14 . Sep 1996 . 8809112 . 10.1016/0167-4781(96)00101-7 .
• Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K . Alternative splicing generates isoforms of human neuron-derived orphan receptor-1 (NOR-1) mRNA . Gene . 211 . 1 . 79–85 . Apr 1998 . 9573341 . 10.1016/S0378-1119(98)00095-X .
• Labelle Y, Bussières J, Courjal F, Goldring MB . The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator . Oncogene . 18 . 21 . 3303–8 . May 1999 . 10359536 . 10.1038/sj.onc.1202675 . 21623156 .
• Panagopoulos I, Mencinger M, Dietrich CU, Bjerkehagen B, Saeter G, Mertens F, Mandahl N, Heim S . Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11) . Oncogene . 18 . 52 . 7594–8 . Dec 1999 . 10602519 . 10.1038/sj.onc.1203155 . 31905291 .
• Sjögren H, Wedell B, Meis-Kindblom JM, Kindblom LG, Stenman G, Kindblom JM . Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21) . Cancer Research . 60 . 24 . 6832–5 . Dec 2000 . 11156374 .
• Liu D, Jia H, Holmes DI, Stannard A, Zachary I . Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1 . Arteriosclerosis, Thrombosis, and Vascular Biology . 23 . 11 . 2002–7 . Nov 2003 . 14525795 . 10.1161/01.ATV.0000098644.03153.6F . free .
• Rius J, Martínez-González J, Crespo J, Badimon L . Involvement of neuron-derived orphan receptor-1 (NOR-1) in LDL-induced mitogenic stimulus in vascular smooth muscle cells: role of CREB . Arteriosclerosis, Thrombosis, and Vascular Biology . 24 . 4 . 697–702 . Apr 2004 . 14962944 . 10.1161/01.ATV.0000121570.00515.dc . free .
• Hisaoka M, Okamoto S, Yokoyama K, Hashimoto H . Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas without detectable NR4A3 fusion genes . Cancer Genetics and Cytogenetics . 152 . 2 . 101–7 . Jul 2004 . 15262426 . 10.1016/j.cancergencyto.2003.11.011 .
• Laflamme C, Filion C, Labelle Y . Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1 . Human Mutation . 24 . 6 . 502–8 . Dec 2004 . 15523651 . 10.1002/humu.20102 . 42925900 . free .
• Rius J, Martínez-González J, Crespo J, Badimon L . NOR-1 is involved in VEGF-induced endothelial cell growth . Atherosclerosis . 184 . 2 . 276–82 . Feb 2006 . 15949808 . 10.1016/j.atherosclerosis.2005.04.008 .
• Pei L, Castrillo A, Chen M, Hoffmann A, Tontonoz P . Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli . The Journal of Biological Chemistry . 280 . 32 . 29256–62 . Aug 2005 . 15964844 . 10.1074/jbc.M502606200 . free .
• Bonta PI, van Tiel CM, Vos M, Pols TW, van Thienen JV, Ferreira V, Arkenbout EK, Seppen J, Spek CA, van der Poll T, Pannekoek H, de Vries CJ . Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses . Arteriosclerosis, Thrombosis, and Vascular Biology . 26 . 10 . 2288–94 . Oct 2006 . 16873729 . 10.1161/01.ATV.0000238346.84458.5d . free .
• Pearen MA, Ryall JG, Maxwell MA, Ohkura N, Lynch GS, Muscat GE . The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle . Endocrinology . 147 . 11 . 5217–27 . Nov 2006 . 16901967 . 10.1210/en.2006-0447 . free .
• Pearen MA, Myers SA, Raichur S, Ryall JG, Lynch GS, Muscat GE . The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle . Endocrinology . 149 . 6 . 2853–65 . Jun 2008 . 18325999 . 10.1210/en.2007-1202 . free .
• Vacca M, Murzilli S, Salvatore L, Di Tullio G, D'Orazio A, Lo Sasso G, Graziano G, Pinzani M, Chieppa M, Mariani-Costantini R, Palasciano G, Moschetta A . Neuron-derived orphan receptor 1 promotes proliferation of quiescent hepatocytes . Gastroenterology . 144 . 7 . 1518–1529.e3 . Jun 2013 . 23462179 . 10.1053/j.gastro.2013.02.027 . free .

Notes and References

1. Hedvat CV, Irving SG . The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor . Molecular Endocrinology . 9 . 12 . 1692–700 . Dec 1995 . 10.1210/mend.9.12.8614405 . 8614405 . free .
2. Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS . β-Cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion . Am J Physiol Endocrinol Metab . 311 . 1 . E186–201 . July 2016 . 27221116 . 10.1152/ajpendo.00022.2016 . free .
3. Pearen MA, Ryall JG, Maxwell MA, Ohkura N, Lynch GS, Muscat GE . The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle . Endocrinology . 147 . 11 . 5217–27 . Nov 2006 . 16901967 . 10.1210/en.2006-0447 . free .
4. Pearen MA, Myers SA, Raichur S, Ryall JG, Lynch GS, Muscat GE . The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle . Endocrinology . 149 . 6 . 2853–65 . Jun 2008 . 18325999 . 10.1210/en.2007-1202 . free .
5. Nomiyama T, Nakamachi T, Gizard F, Heywood EB, Jones KL, Ohkura N, Kawamori R, Conneely OM, Bruemmer D . The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation . The Journal of Biological Chemistry . 281 . 44 . 33467–76 . Nov 2006 . 16945922 . 1829169 . 10.1074/jbc.M603436200 . free .
6. Laflamme C, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y . The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas . Cancer Research . 63 . 2 . 449–54 . Jan 2003 . 12543801 .
7. Ohkura N, Ohkubo T, Maruyama K, Tsukada T, Yamaguchi K . The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3 . Developmental Neuroscience . 23 . 1 . 17–24 . 2001 . 11173923 . 10.1159/000048692 . 84167063 .