NR4A1

Official Full Name

nuclear receptor subfamily 4 group A member 1

Organism

Homo sapiens

GeneID

3164

Background

This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

Synonyms

HMR; N10; TR3; NP10; GFRP1; NAK-1; NGFIB; NUR77;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

Nuclear receptors (NR) are a class of ligand-dependent transcription factor subfamilies distributed in the cytoplasm or nucleus and are abundant in multicellular organisms. NR4A1 is a member of the NR4A family, which is classified as an early response gene family. It can be induced quickly and briefly by some stimuli including cyclic adenosine phosphate, phorbol esters, growth factors, peptide hormones, neurotransmitters, membrane depolarization, mechanical agitation, and magnetic fields. Studies have shown that NR4A1 functions as a response protein in the early stages of signal transduction.

Nr4a1 Figure 1. The important role of NR4A1 in GC cell apoptosis induced by TNFα. (Yan, H., et al. 2017)

The Biological Function of NR4A1

The function of NR4A1 varies depending on cell type and stimulus signal. In recent years, the biological function of NR4A1 has been studied through various methods such as analysis of the promoter region of the target gene of NR4A1, NR4A1 overexpression and suppression experiments based on cell culture, and establishment of animal (mouse) NR4A1 knockout models. The overexpression of NR4A1 can antagonize the ceramide-induced apoptosis of mature B-lymphoma cells, and has the functions of pro-survival and anti-apoptosis. However, in B-lymphoma, the overexpression of NR4A1 does not antagonize FasL-induced apoptosis, which may mean that NR4A1 does not participate in Fas-mediated apoptosis.

Studies have found that β-adrenergic receptor agonists can induce the production of NR4A1 in neurons cultured in vitro and can cause the release of norepinephrine in the rat cerebral cortex. In skeletal muscle cells cultured in vivo or in vitro, β-adrenaline can transiently induce NR4A1 mRNA expression, and this expression can be inhibited by β-adrenergic receptor antagonists. In denervated skeletal muscle, the expression of NR4A1 decreased significantly, indicating that the sympathetic nerve played a role in the expression of NR4A1.

NR4A1 and Atherosclerosis

NR4A1 is an important transcription factor in the regulation of vascular gene expression and plays a key role in vascular remodeling, such as cell survival, proliferation, and inflammation. Endothelial cell injury, accompanied by the expression of adhesion molecules and the ensuing recruitment of circulating monocytes, is an important event at the beginning of atherosclerosis. In endothelial cells, NR4A1 can be effectively induced by a variety of atherosclerotic stimuli, including atherosclerotic lipoprotein, inflammatory cytokines, growth factors, and hypoxia. The researchers analyzed the genome of human vascular smooth muscle cells stimulated by inflammatory cytokines and growth factors secreted by activated macrophages and found that NR4A1 was significantly induced. This is the first time that NR4A1 is associated with vascular smooth muscle cells under pathological conditions.

In a study of 14 vascular samples of AS patients at different pathological stages, it was found that NR4A1 was significantly abnormal in the neointimal vascular smooth muscle cells. However, no expression was found in the normal media of blood vessels (consisting of vascular smooth muscle cells). Subsequently, the researchers constructed a transgenic mouse model. Compared with wild-type mice, up-regulating the expression of NR4A1 can significantly inhibit the proliferation of vascular smooth muscle cells and neointimal formation caused by carotid ligation. In addition, NR4A1 can maintain the normal smooth muscle cell phenotype, contraction phenotype, by regulating the expression of blood vessel smooth muscle cell-specific marker proteins, such as α-actin and calcium-binding protein. Using the carotid artery ligation model study, it was found that compared with the wild type and the NR4A1 gene knockout mice, NR4A1 overexpression transgenic mice due to blood flow changes caused by the remodeling of blood vessels are significantly reduced. The mechanism may be by reducing macrophage infiltration and lowering the expression level of metalloproteinase-2 (MMP-2) in vascular smooth muscle cells rather than regulating vascular tension.

References:

Yan, H. , Xiao, F. , Zou, J. , Qiu, C. , Sun, W. , & Gu, M. , et al. (2017). Nr4a1-induced increase in the sensitivity of a human gastric cancer line to tnfα-mediated apoptosis is associated with the inhibition of jnk/parkin-dependent mitophagy. International Journal of Oncology.
Egarnes, B. , Marie-Renée Blanchet, & Gosselin, J. . (2017). Treatment with the nr4a1 agonist cytosporone b controls influenza virus infection and improves pulmonary function in infected mice. Plos One, 12(10), e0186639.
Zhang, Y. , Chen, G. , Gao, B. , Li, Y. , & Zhu, B. . (2016). Nr4a1 knockdown suppresses seizure activity by regulating surface expression of nr2b. Scientific Reports, 6, 37713.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry