Disease relevance of NR1H2

• NER, a new member of the steroid hormone nuclear receptor (NR)-encoding gene family, was isolated from a human osteosarcoma SAOS/B10 cell line cDNA library [1].
• The nominal associations of LXRA and LXRB alleles with obesity are interesting and should be further investigated in independent data sets [2].
• The aims of this study were to determine: (i) whether oxysterols applied topically to the skin of mice induce differentiation in normal epidermis; (ii) whether this effect is mediated via liver X receptor-alpha and/or liver X receptor-beta; and (iii) whether oxysterols normalize epidermal morphology in an animal model of epidermal hyperplasia [3].
• Our previous experiments have suggested that a major autosomal recessive gene and several minor genes regulate the inheritance of tonic-clonic seizures in NER [4].
• RESULTS: After the F9 generation, 94%-98% of NER exhibited spontaneous tonic-clonic convulsions, beginning with neck and forelimb clonus, wild jumping/running, opisthotonic posturing, and evolving to tonic, then clonic convulsion, followed by postictal flaccidity [5].

Psychiatry related information on NR1H2

• Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease [6].
• NER revealed seizure susceptibility to pentylenetetrazol, tossing, and transcorneal electroshock, but not to tactile, photic, or acoustic stimuli, or to transauricular electroshock [5].

High impact information on NR1H2

• International Union of Pharmacology. LXII. The NR1H and NR1I Receptors: Constitutive Androstane Receptor, Pregnene X Receptor, Farnesoid X Receptor {alpha}, Farnesoid X Receptor beta, Liver X Receptor {alpha}, Liver X Receptor beta, and Vitamin D Receptor [7].
• Interestingly, NER-type DNA damage further stabilizes XPC and thereby enhances repair [8].
• Knockout mice revealed that mHR23A and mHR23B have a fully redundant role in NER, and a partially redundant function in embryonic development [8].
• The CAK kinase inhibitor H-8 improved repair efficiency, indicating that CAK can negatively regulate NER by phosphorylation [9].
• Here, we show that UNR mRNA translation and UNR IRES activity are significantly increased during mitosis [10].

Chemical compound and disease context of NR1H2

• Biopsies from 131 women with squamous cell carcinoma of the cervix diagnosed between May 1983 and July 1986 were assayed for nuclear and "cytoplasmic" estrogen receptors (NER and CER) [11].
• These experiments examined the effects of a high and a low dose of estradiol benzoate (EB) in enhancing lordosis behavior and correlated these effects with the retention of hypothalamic nuclear estrogen receptors (NER) in female hamsters [12].
• Nuclear estradiol receptors (NER) were measured in human breast carcinomas by extracting nuclei with 0.6 mol/l KCl and adsorption to hydroxylapatite [13].

Biological context of NR1H2

• As part of this analysis, we have assessed the NR1H2 gene on chromosome 19 and report here a modest association with the locus in sibpairs with late onset disease [6].
• NER codes for a polypeptide of 461 amino acids which contains the conserved sequences of the DNA-binding and ligand-binding domains of typical steroid hormone NR [1].
• The LXRA and LXRB genes were screened for polymorphisms and common single nucleotide polymorphisms genotyped in obese and nonobese women [2].
• OBJECTIVE: LXRA and LXRB genes regulate adiposity, energy dissipation, as well as glucose and lipid homeostasis in mice [2].
• Mitosis (NEB to NER) is twice as long in Colcemid-treated eggs as in the untreated controls [14].

Anatomical context of NR1H2

• METHODS: LXRA and LXRB mRNAs were quantified in abdominal subcutaneous adipose tissue of obese and nonobese women [2].
• Whereas both liver X receptor-alpha and liver X receptor-beta are expressed in cultured human keratinocytes and in fetal rat skin, only liver X receptor-beta was observed on northern blotting in adult mouse epidermis [3].
• These eggs show repeated cycles of nuclear envelope breakdown (NEB) and nuclear envelope reformation (NER) [14].
• The relative amount of NER carried out by a TTD183ME fibroblast cell strain after ultraviolet (UV) exposure was approximately 65% of normal as determined by a method that converts repair patches into quantifiable DNA breaks [15].
• These are known to be chiefly repaired by both nucleotide (NER) and base (BER) excision repair in eukaryotic cells [16].

Associations of NR1H2 with chemical compounds

• In this study, we identified the first nonoxysterol natural product that functions as a ligand for the liver X receptor (LXRalpha and LXRbeta; NR1H3, NR1H2), a NHR that acts as the receptor for oxysterols and plays a key role in regulation of cholesterol metabolism and transport as well as glucose metabolism [17].
• The x-ray crystal structures of the human liver X receptor beta ligand binding domain complexed to sterol and nonsterol agonists revealed a perpendicular histidinetryptophan switch that holds the receptor in its active conformation [18].
• Although no ligand was identified for NER-I, its wide distribution may indicate that this novel steroid hormone NR may play a basic role in cell function [1].
• We have detected frequent alternative splicing of a gene that encodes NER, a protein homologous to the retinoic acid receptors, in cancer cells [19].
• Relative mutation frequencies increased with the adduct level, with 1.3-3.6-fold higher numbers of mutations in the XP cells compared to the GM00637 cells, indicating that NER plays a significant role in the removal of these particular tamoxifen DNA adducts [20].

Other interactions of NR1H2

• The present work shows that the acetyl-podocarpic dimer (APD) is a potent, selective agonist for both LXRalpha (NR1H3) and LXRbeta (NR1H2) [21].
• Plausible positional candidate genes include NR1H2 and TULP2 [22].
• A reciprocal analysis showed that each human receptor had one or more Fugu orthologs, excepting CAR (NR1I3) and LXRbeta (NR1H2) [23].
• We characterize the ability of the liver X receptor (LXRalpha [NR1H3] and LXRbeta [NR1H2]) agonist, T0901317, to activate the farnesoid X receptor (FXR [NR4H4]) [24].

Analytical, diagnostic and therapeutic context of NR1H2

• Recent data suggest that the nuclear transcription factors liver X receptor-alpha and liver X receptor-beta (LXRalpha and LXRbeta) limit plaque formation in animal models by modulating macrophage function [25].
• Assignment of the human ubiquitous receptor gene (UNR) to 19q13.3 using fluorescence in situ hybridization [26].
• When tumors were assayed for CER, nuclear estrogen receptor (NER), and cytoplasmic progesterone receptor (CPR), there were no racial differences in the proportions of tumors containing all 3 receptors, but significant variations were found in neoplasms with no receptors and in those with apparently defective receptors [27].
• Furthermore, there was evidence of interaction between LXRA and LXRB alleles in determining body mass index [2].
• Northern blot analysis indicates that RIP14 is expressed specifically in liver and kidney, while RIP15 is expressed in every tissue tested [28].

References