Nuclear receptor 4A (NR4A) family - orphans no more

Authors

• Stephen Safe, Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA. Electronic address: ssafe@cvm.tamu.edu.
• Un-Ho Jin, Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
• Benjamin Morpurgo, Texas A&M Institute for Genomic Medicine, Texas A&M University, 670 Raymond Stotzer Pkwy, College Station, TX 77843, USA.
• Ala Abudayyeh, Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
• Mandip Singh, Department of Pharmaceutics, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
• Ronald B. Tjalkens, Department of Toxicology and Neuroscience, Colorado State University, 1680Campus Delivery, Fort Collins, CO 80523-1680, USA.

Document Type

Article

Abstract

The orphan nuclear receptors NR4A1, NR4A2 and NR4A3 are immediate early genes induced by multiple stressors, and the NR4A receptors play an important role in maintaining cellular homeostasis and disease. There is increasing evidence for the role of these receptors in metabolic, cardiovascular and neurological functions and also in inflammation and inflammatory diseases and in immune functions and cancer. Despite the similarities of NR4A1, NR4A2 and NR4A3 and their interactions with common cis-genomic elements, they exhibit unique activities and cell-/tissue-specific functions. Although endogenous ligands for NR4A receptors have not been identified, there is increasing evidence that structurally-diverse synthetic molecules can directly interact with the ligand binding domain of NR4A1 and act as agonists or antagonists, and ligands for NR4A2 and NR4A3 have also been identified. Since NR4A receptors are key factors in multiple diseases, there are opportunities for the future development of NR4A ligands for clinical applications in treating multiple health problems including metabolic, neurologic and cardiovascular diseases, other inflammatory conditions, and cancer.

Keywords

Multiple functions, NR4A, Novel ligands, Nuclear receptors

Medical Subject Headings

Arthritis (metabolism); Cardiovascular Diseases (metabolism); DNA-Binding Proteins (metabolism); Homeostasis; Humans; Immunity, Cellular; Inflammation (metabolism); Ligands; Metabolic Diseases (genetics, metabolism); Neoplasms (metabolism); Nuclear Receptor Subfamily 4, Group A, Member 1 (genetics, metabolism); Nuclear Receptor Subfamily 4, Group A, Member 2 (genetics, metabolism); Receptors, Steroid (metabolism); Receptors, Thyroid Hormone (metabolism)

Publication Date

3-1-2016

Publication Title

The Journal of steroid biochemistry and molecular biology

E-ISSN

1879-1220

Volume

157

First Page

48

Last Page

60

PubMed ID

25917081

Digital Object Identifier (DOI)

10.1016/j.jsbmb.2015.04.016

Recommended Citation

Safe, Stephen; Jin, Un-Ho; Morpurgo, Benjamin; Abudayyeh, Ala; Singh, Mandip; and Tjalkens, Ronald B., "Nuclear receptor 4A (NR4A) family - orphans no more" (2016). Translational Neuroscience. 2552.
https://scholar.barrowneuro.org/neurobiology/2552