Abstract
In this chapter, we summarize the birth of the field of nuclear receptors. These receptors exhibit a multitude of roles in cell biology and hence have attracted a great deal of interest in the drug discovery field. It is not certain whether these receptors evolved independently or an ancestral protein acquired various functions upon binding to preexisting small molecules, ligands. Currently, members of this receptor superfamily are categorized in six groups, including “orphan receptors.” Research in the area has resulted in several clinically used drugs and continues to reveal further previously unknown roles for these receptors paving the road toward more valuable discoveries in the future.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- CAR:
-
Constitutive androstane receptor
- COUP-TFII:
-
COUP transcription factor II receptor
- ERRs:
-
Estrogen-related receptors
- GCNF1:
-
The germ cell nuclear factor-1
- HNF-4:
-
Hepatocyte nuclear factor-4 receptor
- LXRs:
-
Liver X receptors
- NGFI-B, NURR1, and NOR1:
-
The nerve growth factor induced clone B group of orphan receptors
- NR5A1:
-
The steroidogenic factor 1
- PPARs:
-
Peroxisome proliferator-activated receptors
- PXR:
-
Pregnane X receptor
- RARs:
-
Retinoic acid receptor
- Rev-Erb, ROR:
-
Receptor tyrosine kinase-like orphan receptors
- RXRs:
-
Retinoid X receptor
- TRs:
-
Thyroid hormone receptor
- VDR:
-
Vitamin D receptor
References
Shi Y (2007) Orphan nuclear receptors in drug discovery. Drug Discov Today 12:440–445. PMC. Web. 22 July 2018
Hoffmann JM, Partridge L (2015) Nuclear hormone receptors: roles of xenobiotic detoxification and sterol homeostasis in healthy aging. Crit Rev Biochem Mol Biol 50(5):380–392
Ranhotra HS (2013) The orphan nuclear receptors in cancer and diabetes. J Recept Signal Transduct Res 33(4):207–212
Lonard DM, O'Malley BW (2012) Nuclear receptor coregulators: modulators of pathology and therapeutic targets. Nat Rev Endocrinol 8(10):598–604
Malek G, Lad EM (2014) Emerging roles for nuclear receptors in the pathogenesis of age-related macular degeneration. Cell Mol Life Sci 71(23):4617–4636
Kadmiel M, Cidlowski JA (2013) Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci 34(9):518–530
Oyekan A (2011) PPARs and their effects on the cardiovascular system. Clin Exp Hypertens 33(5):287–293
Youssef J, Badr M (2015) Peroxisome proliferator-activated receptors: features, functions, and future. Nucl Recep Res 2:Article ID 101188. https://doi.org/10.11131/2015/101188
Gawienowski AM, Gibbs CC (1968) Identification of cholesterol and progesterone in apple seeds. Steroids 12(4):545–550
Simons RG, Grinwich DL (1989) Immunoreactive detection of four mammalian steroids in plants. Can J Bot 67(2):288–296
Weigel NL, Zhang Y (1998) Ligand-independent activation of steroid hormone receptors. J Mol Med (Berl) 76(7):469–479
Zwijsen RM et al (1998) Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1. Genes Dev 12(22):3488–3498
Bennesch MA, Picard D (2015) Minireview: tipping the balance: ligand-independent activation of steroid receptors. Mol Endocrinol 29(3):349–363
Jensen EV (1962) On the mechanism of estrogen action. Perspect Biol Med 6:47–59
Jensen EV, Greene GL, Closs LE, DeSombre ER, Nadji M (1982) Receptors reconsidered: a 20-year perspective. Recent Prog Horm Res 38:1–40
Nuclear Receptors Nomenclature Committee (1999) A unified nomenclature system for the nuclear receptor superfamily. Cell 97(2):161–163
Mullican SE, DiSpirito JR, Lazar MA (2013) The orphan nuclear receptors at their 25th year reunion. J Mol Endocrinol 51(3):T115–T140
di Masi A et al (2009) Nuclear receptors CAR and PXR: molecular, functional, and biomedical aspects. Mol Asp Med 30(5):297–343. https://doi.org/10.1016/j.mam.2009.04.002. Epub 2009 May 7
Willson TM, Moore JT (2002) Genomics versus orphan nuclear receptors—a half-time report. Mol Endocrinol 16:1135–1144
Acknowledgments
The authors acknowledge the financial support of the following agencies: M.D.G. from ANPCyT (PICT 2016-0545), UBACYT, and Instituto Nacional del Cáncer; G.I.M. from ANPCyT (PICT 2016-2607). M.B.C., J.C.S, and O.B.S. are partially supported by the Research Centers in Minority Institutions (RCMI) program, grant 2G12MD007592 to the Border Biomedical Research Center (BBRC) at UTEP, from the National Institutes on Minority Health and Health Disparities (NIMHD), a component of the NIH. M.B.C. is also supported by the Department of Defense (DOD) Prostate Cancer Research Program (PCRP) through grant number W81XWH-17-1-0435.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Mazaira, G.I. et al. (2019). Nuclear Receptors: A Historical Perspective. In: Badr, M. (eds) Nuclear Receptors. Methods in Molecular Biology, vol 1966. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9195-2_1
Download citation
DOI: https://doi.org/10.1007/978-1-4939-9195-2_1
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-4939-9194-5
Online ISBN: 978-1-4939-9195-2
eBook Packages: Springer Protocols