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- Table of Contents
Facts about Nuclear receptor subfamily 4 group A member 2.
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Human | |
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Gene Name: | NR4A2 |
Uniprot: | P43354 |
Entrez: | 4929 |
Belongs to: |
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nuclear hormone receptor family |
human homolog of; NGFI-B beta; NOT; NR4A2; nuclear receptor subfamily 4, group A, member 2; Nurr1; orphan nuclear receptor NR4A2; Orphan nuclear receptor NURR1; T-cell nuclear receptor NOT; TINUR; transcriptionally inducible nuclear receptor related 1; Transcriptionally-inducible nuclear receptor
Mass (kDA):
66.591 kDA
Human | |
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Location: | 2q24.1 |
Sequence: | 2; NC_000002.12 (156324432..156332724, complement) |
Expressed in a number of cell lines of T-cell, B-cell and fibroblast origin. Strong expression in brain tissue.
Cytoplasm. Nucleus. Mostly nuclear; oxidative stress promotes cytoplasmic localization.
Ionizing radiation-induced PARylation is an atypical target for the NR4A2 marker. This marker is essential in controlling the expression of genes and is important in the differentiation of signalling which is co-regulated by the NR4A2 and NR4A3 proteins. This article will discuss the most effective applications of this marker. We will examine how the NR4A2 marker modulates the expression of genes in monocytes.
NR4A2 is a major Ionizing radiation-induced PARylated Protein. This protein has been implicated in the process of tumorigenesis. This mutant was utilized as a reporter gene. EGFP and NR4A2 were transiently transfected into U2OS cells. Transfections using NR4A2 mutants induced a high amount of PAR in cells of the cA1/A2 line.
Poly-ADP-ribosylation of DNA repair factors has been widely studied, but the mechanisms of PARylation remain poorly understood. Before, NR4A's nuclear orphan receptors were associated with DSB repair. They serve as transcription factors and contain a tandem zinc-finger DNA binding domain (DBD). The DBD of NR4A is bound to polyADP-ribose and assists in DNA-PK kinase assembly at DNA lesions. By targeting the NR4A DBD enables cancer therapy.
Jurkat cells showed the effect of IR upon NR4A2 They also had high levels of ACA-sensitive currents due to IR. Additionally, the phosphorylation process of NR4A2 is a well-known ionizing radiation target. Additionally radiation-induced PARylation caused DNA repair and both of these processes affect mitochondrial functions.
PARP inhibits TNKS1BP1 activity. This means that TNKS1BP1 could be as a therapeutic target for ionizing radiation-induced PARylation. Additionally, it can sensitize childhood high-grade glioma cells to the PARY-induced DNA-PKcs. Therefore, PARP inhibition may increase radiotherapy effectiveness.
Researchers discovered that ionizing radiation caused RNA damage that raised the expression of NR4A2 in the latest study. The cellular response protein that is involved in mitotic progress was identified as poly(ADPribose Polymerase-3. They identified a novel cellular reaction protein, PAP3G that coimmunoprecipitates well with NR4A2(Raptor). They also found that RAF was blocked by an variant of NR4A2 that lacks the Lys840 spot for acetylation.
These observations are consistent with those observed in humans. Despite the fact that NR4A2 is an important target for ionizing radiation, its impact on the human cancer cells is largely undetermined. It isn't yet clear if radiation-induced PARylation causes the desired effect in humans. However scientists remain hopeful and continue to look for a medication that can stop or reduce NR4A2.
Furthermore, Jurkat cells are subject to G2/M cell cycle inhibition due to radiation ionizing. This suggests that IR might affect GTPase signaling and Ca2+ signaling. Fluo-3 fluorescence is dependent on the side scatter of Jurkat cell. Fluo-3 fluorescence can be used to determine the Ca2+ concentration in the cytosol. High levels of Ca2+ are apparent in the high cytosolic levels.
NR4As regulate transcription by binding directly to DNA. Additionally they function as heteromers, homomers, or monomers to control the expression of particular genes. They target genes involved in cell proliferation and survival as well as inflammation. These molecules are crucial for cellular functions including immune responses. Boster Bio's NR4A2 marker modulates gene expression in the human the spleen.
Researchers discovered that miR137 acted on NR4A2 via the Notch pathway. The results of the experiments showed that miR-137 decreased the activity of luciferase mutant and wild-type NR4A2 cells. These results were consistent with previous studies that showed miR137 inhibits Notch. Similar results were observed with miR-137 in breast cancer cells.
This study has important clinical implications. NR4A is involved with the decidualization human embryonic stem cell cells. It also regulates the expression of insulin-like growth factor binding protein-1. Female females who are infertile are afflicted by a absence of the uterine Nr4A1. Also, loss of FOXO1A could inhibit PRL and IGFBP-1. Female infertility can be caused by decreased expression of NR4A2 within the human ejaculatory Stroma.
Another study published by Zimprich et al. (2003) assessed the role of NR4A2 in familial Parkinson disease (PD). Researchers discovered that the gene is responsible foxO1A's expression. This gene is involved in the production of dopamine within the brain. Mutations of NR4A2 may lead to the development of Parkinson's.
The RNAseq dataset was analysed using the NR4A2 marker and the p-values generated by the Wald test. The NR4A2 promoter was effectively recovered from Flag-NR4A immunoprecipitates, but not the LacZ control. There was no PCR product available for the LacZ control. This suggests that the RNAseq marker could be utilized in an environment of clinical testing to determine the expression of genes.
Furthermore, NR4A2 marker suppresses p-p65 in human lung cancer cells. This gene is also involved in the regulation and activation of inflammation as well as apoptosis. When overexpressed, it promotes the production of apoptotic and inflammation mediators. Nurr1 may block the methylation of p65 which reduces the expression of these genes. It also blocks the signaling pathway that regulates NF-kB.
Nuclear receptors (NRs) are membrane proteins that have multiple domains that affect transcription. They are able to bind DNA as homomer or monomer and regulate the expression of important genes involved in cellular processes, such as cell survival and proliferation. They also facilitate signalling between tissues, cells, and cells. Because of their important roles in the cell, these receptors represent therapeutic targets.
DKO thymocytes show a greater negative selection than WT. CD4SP DKO mice have four to six times the amount of thymocytes as cells in WT. This suggests that the majority of the negative selection in mice is caused by NR4A dependent deletion. Furthermore, previous studies implicate the NR4A family in negative selection of cells via the ubiquitous and tissue-restricted antibodies.
Numerous studies have shown that NR4A3 is implicated in the onset and progression of many diseases that include obesity, diabetes, atherosclerosis as well as inflammation and diabetes. Recent research also shows that NR4A3 has a role in regulating the release of hormones in the human brain.
Additionally, in vivo have revealed that NR4A3 has cell-intrinsic roles in the thymic development. The regulation of ERK expression in a tumor-associated macrophage cell line is also an effect of the NR4A3 gene. It isn't known what role NR4A3 plays in cancer.
Western analysis of blots is used to measure the expression of proteins. The experiments included blocking nitrocellulose membranes with blocking buffer, incubating with primary antibodies overnight, and washing them five times with 1xTBST. Secondary antibodies were used to detect the signal following in vitro stimulation. We also used a FOXP3/transcribing factor buffer set from eBioscience.
Knockdowns of NR4A3 have a broad effect on gene expression, in contrast to NR4A2, that only regulates signalling, which is only controlled by NR4A2. The results also show which DEGs were significantly up - or down-regulated by NR4A3 knockdown.
Similar to this, Nor1 inhibits the growth of tumor cells by interfering with their metabolism. It also blocks autophagy, suppressing autophagy-induced melanoma cells. A knockdown of Nor1 also blocks the formation of LC3-II.
The expression of genes in monocytes is controlled by the genes regulatory proteins NR4A2 (or NR4A3). Both NR4As work as receptors for interferon-alpha, which is a signalling molecule that controls the production of cytokines. These proteins are controlled by different ligands. This dual regulation of gene expression could result from the existence of redundant signalling pathways or distinct cell functions.
NR4A2 and NR4A3 both are active, constitutively active nuclear receivers with distinct roles the homeostasis of immune cells. Both proteins are abundant in gene clusters that are linked to antigen processing and the presentation of antigens and the response of cells to interferon-alpha. These proteins have similar levels of gene expression monocytes that have been stimulated as well as unstimulated.
Additionally, NR4A2 is an important regulator of numerous genes in the body, including those involved in inflammation. PGE2 increases NR4A2 expression and within an hour, NR4A2 mRNA increased 14-fold. After 24 hours, NR4A2 mRNA decreased to the levels of baseline. Additionally, the expression of PRL increases from 4 to 43 times. These results suggest that NR4A2 is an early gene induction factor for PRL.
The gene NR4A2 has been linked to PR/SET Domain 6 MCF2, HUNK, and PR/SET Domain 6 as well as other. These genes are affected by NR4A2-activated receivers. NR4A2 is also associated with calcium channel-related genes such as CACNA2D1.
The gene NR4A2 is responsible for the expression of PRL in synoviocytes of humans. PRL is an immunomodulatory peptide hormone involved in inflammation and autoimmune diseases. NR4A2 increases the levels of PRL mRNA and secretes PRL-specific protein in K4IM cells. The removal of the endogenous NR4A receptors decreased PRL levels by 95 percent. Additionally, PRL expression is triggered by NR4A2 which requires an active DNA binding domain in order to activate the PRL promoter region in the distal region.
As mentioned previously Boster Bio's NR4A2-based binding ligands (RIL) are different in structure and function as agonists and antagonists. Recently, NR4A3 ligands were identified. The group of ligands known as NR4A is recognized to regulate gene expression through modifications in mRNA levels post-translational modification, and protein synthesis. It also acts as transcriptional regulators and binds directly to the promoter region of targeted genes.
PMID: 7877627 by Mages H.W., et al. NOT, a human immediate-early response gene closely related to the steroid/thyroid hormone receptor NAK1/TR3.
PMID: 10216262 by Ichinose H., et al. Molecular cloning of the human Nurr1 gene: characterization of the human gene and cDNAs.