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The protein encoded by this gene is a receptor for glucocorticoids and can act as both a transcription factor and a regulator of other transcription factors. The encoded protein can bind DNA as a homodimer or as a heterodimer with another protein such as the retinoid X receptor. This protein can also be found in heteromeric cytoplasmic complexes along with heat shock factors and immunophilins. The protein is typically found in the cytoplasm until it binds a ligand, which induces transport into the nucleus. Mutations in this gene are a cause of glucocorticoid resistance, or cortisol resistance. Alternate splicing, the use of at least three different promoters, and alternate translation initiation sites result in several transcript variants encoding the same protein or different isoforms, but the full-length nature of some variants has not been determined. A possible indicastion for selection of synthetic glucocorticoids for treatment of pathological conditions in which hGR beta modulates the sensitivity of tissues to glucocorticoids. AUUUA motifs in the 3'UTR of human glucocorticoid receptor alpha and beta mRNA destabilize mRNA and decrease receptor protein expression. Association of coronary artery disease with glucocorticoid receptor N363S variant. Carboxyl terminus of the ligand-binding domain is extremely important in conferring transactivational activity by altering multiple functions of this composite transcription factor. Corticosteroid receptor beta. CRbeta functions as an endogenous inhibitor of corticosteroids and may play a role in steroid resistance. RA patients have enhanced CRbeta expression in PMBCs. Data report the crystal structures of two overlapped fragments of FK506-binding protein 52 and the heterocomplex of glucocorticoid receptors with heat-shock proteins 90. Data show that differential recruitment of coactivators by progesterone and glucocorticoid receptors determines the assembly of coactivator complexes on target promoters to mediate specific transcription signals. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor. Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene. Functional interaction between the pro-apoptotic DAP3 and the glucocorticoid receptor. GR enhances pregnane X receptor mediated glucuronosyltransferase isozyme 1 and protein in hepatoma cell line. GR mRNA expression was reduced in the basolateral/lateral nuclei in schizophrenia and bipolar disorder. GRalpha transcripts containing exons 1A3, 1B, and 1C contribute most to the intracellular level of GR mRNA and may be the most relevant for steroid-mediated apoptosis in T-lymphoblasts. Glucocorticoid receptor activates Bcl-XL during tumorigenesis. Glucocorticoid receptor alpha is expressed in adenotonsillar tissue of children with obstructive sleep apnea. Glucocorticoid receptor binding in twin pairs is affected by shared environment but not by shared genes. Glucocorticoid receptor blocks P-TEFb recruitment by NFkappaB to effect promoter-specific transcriptional repression. Glucocorticoid receptor-induced MPK-1 expression inhibits paclitaxel-associated MAPK activation and contributes to breast cancer cell survival. Identification of the novel GRV575M variant in human bronchial epithelial cells using a molecular genetic selection scheme. Ligand binding induces a conformational change dependent on ligand affinity. This decreases receptor mobility, probably by targeting it to relatively immobile nuclear domains with which it transiently associates. This also blocks immobilization by MG132. New, alternatively spliced transcripts of glucocorticoid receptor alpha subunit may have physiologically relevant roles that might be manifested in a cell type-specific manner and could potentially affect hormone sensitivity or resistance in leukemia. PPARalpha has a role in CYP4X1 regulation, and the glucocorticoid and progesterone receptors have roles in CYP4Z1 gene activation. REVIEW: pathological and in vitro mutations and polymorphisms. Relatively frequent SNP Asn363Ser found in Caucasians and African-Americans. Thus, ethnic differences between Japanese and other races are suggested to exist in NR3C1. Results are consistent with a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, facilitates transcription factor binding, and is simultaneously lost from the template. Results identify Hsp90 as a target of HDAC6 and suggest reversible acetylation as a unique mechanism that regulates Hsp90 chaperone complex activity in maturation of the glucocorticoid receptor. Results reveal differential modulatory roles of the protein inhibitor of activated STAT proteins on the transcriptional properties of mineralocorticoid and glucocorticoid receptors. Results suggest that cell-type specific glucocorticoid receptor isoforms generate specificity in glucocorticoid control of transcription in different tissues. Review. The roles of glucocorticoid receptor isoforms alpha and beta in the response to glucocorticoids in asthma are analyzed. Serine-arginine-rich protein p30 directs alternative splicing of glucocorticoid receptor pre-mRNA to glucocorticoid receptor beta in neutrophils. The ER22/23EK polymorphism is associated with a sex-specific, beneficial body composition at young-adult age, as well as greater muscle strength in males. The counteracting action of cortisone against cortisol-induced apoptosis may take place partially through intervention of GC-receptors (GC-Rs), but may also be due to unknown pathway(s) different from those mediated by cellular GC-Rs. The findings show an association between rheumatoid arthritis and a polymorphism in the hGR gene that increased the stability of hGRbeta mRNA. The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Review. The inability of GRR488Q to repress NF-kappaB was not related to its inability to activate target genes through a glucocorticoid response element. The molecular basis for the reduced GC sensitivity was elucidated by investigating the influence of the ER22/23EK polymorphism on synthesis of GR-A and GR-B isoforms. The results of homology modelling of the human glucorticoid receptor (hGR) ligand-binding domain (LBD) based on the ligand-bound domain of the human estrogen receptor alpha (hERalpha) are reported. There was a significantly higher expression of the GR is untreated RA patients than controls. Glucocorticoid treatment was associated with a strongly decreased GR density. These findings suggest that JNK-mediated phosphorylation of the GR-Ser226 enhances GR nuclear export and may contribute to termination of GR-mediated transcription. This study shows that both promoters 1B and 1C are important for the ubiquitous expression of the human glucocorticoid receptor gene. Twelve polymorphisms in the NR3C1 gene were detected, two types of newly found haplotypes were associated with steroid-resistant idiopathic nephrotic syndrome, which might be responsible for steroid-resistance in partial idiopathic nephrotic syndrome. We conclude that the Gbetagamma complex interacts with the GR and suppresses its transcriptional activity by associating with the transcriptional complex formed on GR-responsive promoters. We identified a novel heterozygous mutation (C643R) in the ligand-binding domain in P30/OHK cells. A mutation of the glucocorticoid receptor gene may have a role in development of systemic lupus erythematosus. An induced-fit mechanism gives structure to the glucocorticoid receptor AF1 domain when it encounters TATA box binding protein. Data support the existence of a new pathway involving hSur2 for modulating GR transactivation processes. Discussion of glucocorticoid receptor gene and protein [review]. Glucocorticoid receptor down-regulation and transactivation is mediated by CHIP, an E3 ligase, through the ubiquitin-proteasome pathway. Glucocorticoid receptor has a role in regulation of hypoxia-dependent gene expression. HGRbeta suppresses the transcriptional activity of hGRalpha by competing with hGRalpha for binding to GRIP1, and possibly other p160 coactivators, through its preserved AF-1. Identified genes transcriptionally activated by GR, in a translation-independent manner, in two human cell lines. Interleukin-5 transcription repression by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment. Investigation of dominant negative function of human glucocorticoid receptor beta. Promoter has several different steroid-responsive sequences. Relaxin acts as GR agonist--a pathway pivotal to its effects on cytokine secretion by human macrophages. Role of GR in glucocorticoid-regulated gene expression. Study suggests that, in men developing obesity early in life, polymorphism of the glucocorticoid receptor gene is associated with less adiposity at a given body mass index, leading to higher insulin sensitivity. The interaction between PPARgamma and GR may be responsible for the additive and synergistic inhibition of chemokine expression by PPARgamma agonists, glucocorticoids, and beta(2)-agonists. The interferon signaling pathway and the human glucocorticoid receptor gene 1A promoter interact in T-lymphocytes. The ligand-binding domain of GR, but not the DNA-binding domain or the N-terminal activation domain, is required for GR-mediated transrepression of TGF-beta transactivation. The role of Hsp90 in nuclear retention of GR after ligand withdrawal. There are non-hormone-binding receptor forms of glucocorticoid receptor in addition to the native heterocomplex.
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