Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We find that prothymosin alpha (PTalpha) selectively enhances transcriptional activation by the estrogen receptor (ER) but not transcriptional activity of other nuclear hormone receptors. This selectivity for ER is explained by PTalpha interaction not with ER, but with a 37-kDa protein denoted REA, for repressor of estrogen receptor activity, a protein that we have previously shown binds to ER, blocking coactivator binding to ER. We isolated PTalpha, known to be a chromatin-remodeling protein associated with cell proliferation, using REA as bait in a yeast two-hybrid screen with a cDNA library from MCF-7 human breast cancer cells. PTalpha increases the magnitude of ERalpha transcriptional activity three- to fourfold. It shows lesser enhancement of ERbeta transcriptional activity and has no influence on the transcriptional activity of other nuclear hormone receptors (progesterone receptor, glucocorticoid receptor, thyroid hormone receptor, or retinoic acid receptor) or on the basal activity of ERs. In contrast, the steroid receptor coactivator SRC-1 increases transcriptional activity of all of these receptors. Cotransfection of PTalpha or SRC-1 with increasing amounts of REA, as well as competitive glutathione S-transferase pulldown and mammalian two-hybrid studies, show that REA competes with PTalpha (or SRC-1) for regulation of ER transcriptional activity and suppresses the ER stimulation by PTalpha or SRC-1, indicating that REA can function as an anticoactivator in cells. Our data support a model in which PTalpha, which does not interact with ER, selectively enhances the transcriptional activity of the ER but not that of other nuclear receptors by recruiting the repressive REA protein away from ER, thereby allowing effective coactivation of ER with SRC-1 or other coregulators. The ability of PTalpha to directly interact in vitro and in vivo with REA, a selective coregulator of the ER, thereby enabling the interaction of ER with coactivators, appears to explain its ability to selectively enhance ER transcriptional activity. These findings highlight a new role for PTalpha as a coregulator activity-modulating protein that confers receptor specificity. Proteins such as PTalpha represent an additional regulatory component that defines a novel paradigm enabling receptor-selective enhancement of transcriptional activity by coactivators.
...
PMID:Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity. 1093 99

To examine the distribution of mineralocorticoid receptor (MR) and the interactions with glucocorticoid receptor (GR) in the brain, we raised a polyclonal antibody against the transcriptional modulation domain of rat MR using the GST-fusion system. Immunoblotting analysis revealed that this antibody recognized a band with the molecular mass of MR in MR-transfected COS-1 cells and in a homogenate of rat hippocampus, and showed no cross-reactivity with GR. In vitro immunocytochemistry of both primary cultured hippocampal neurons and MR-transfected cells revealed immunoreactivity detected by this antibody in both the cytoplasm and nucleus in the absence of aldosterone (ALD), a specific agonist of MR. After 1 h of treatment with 10(-7) M ALD, the MR-immunoreactivity was accumulated in the nuclear region. In the case of GR-transfected cells, our anti-MR antibody either detected no immunopositive cells in the presence or absence of GR agonist. In our in vivo study, MR-immunoreactivity was observed in the rat hippocampus, where cell nuclei showed immunopositive reactions. These results suggest that our antibody against rat MR shows high specificity for the receptor both in liganded and unliganded forms, with no cross-reactivity to GR, and will be useful for cell biological and neuroanatomical investigations of MR.
...
PMID:In vitro and in vivo immunocytochemistry for the distribution of mineralocorticoid receptor with the use of specific antibody. 1094 Apr 51

The glucocorticoid receptor (GR) is a ligand-induced transcription factor which modulates the transcriptional activity of target genes. Full transcriptional activity of GR is achieved with the help of accessory proteins that are able to interact with GR. We have identified a 95-kDa protein by a blotting technique which utilizes a radioactively labeled DNA-bound GR to detect proteins that bind to this complex. Biochemical purification of this protein followed by protein microsequencing resulted in the identification of human nucleolin. In addition we could show that a GR-deletion mutant localizes to the nucleolus, where nucleolin is one of the most abundant proteins. The binding of nucleolin to this deletion mutant was demonstrated by GST-pull-down experiments. We suggest a biological role of nucleolin in binding of GR in the nucleolus.
...
PMID:Identification of nucleolin as a glucocorticoid receptor interacting protein. 1116 42

Human BAG-1 is an anti-apoptotic protein with four protein isoforms (BAG-1 p50, p46, p33, and p29). BAG-1 p46 was originally isolated in a screen for proteins binding to the glucocorticoid receptor; it binds and modulates the action of several members of the nuclear steroid hormone receptor superfamily. The vitamin D receptor (VDR) is another member of this superfamily, and the vitamin D pathway is important for prevention and therapy of osteoporosis, renal failure, cancer, and psoriasis. Therefore, we investigated the effect of the recently isolated BAG-1 p50 on the vitamin D pathway. By use of Far Western blot analysis and glutathione S-transferase BAG-1 p50 binding assays, BAG-1 p50 was demonstrated to interact with the VDR, and the BAG-1 p50 N-terminus was required. In U87 cells that were stably transfected with BAG-1 p50, binding of the VDR to its response element in electrophoretic mobility shift assays was blocked, enhancement of transcriptional activation was inhibited, cell growth rate was enhanced, cell growth inhibition induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was blocked, and 1,25(OH)2D3-mediated VDR induction was inhibited. These results suggest that BAG-1 p50 is a novel regulator of the vitamin D signaling pathway, and its overexpression may lead to cellular resistance to 1,25(OH)2D3 therapy.
...
PMID:BAG-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway. 1128 54

Phenobarbital (PB) induction of CYP2B genes is mediated by translocation of the constitutively active androstane receptor (CAR) to the nucleus. Interaction of CAR with p160 coactivators and enhancement of CAR transactivation by the coactivators have been shown in cultured cells. In the present studies, the interaction of CAR with the p160 coactivator glucocorticoid receptor-interacting protein 1 (GRIP1) was examined in vitro and in vivo. Binding of GRIP1 to CAR was shown by glutathione S-transferase (GST) pull-down and affinity DNA binding. N- or C-terminal fragments of GRIP1 that contained the central receptor-interacting domain bound to GST-CAR, but the presence of ligand increased the binding to GST-CAR of only the fragments containing the C-terminal region. In gel shift analysis, binding to CAR was observed only with GRIP1 fragments containing the C-terminal region, and the binding was increased by a CAR agonist and decreased by a CAR antagonist. Expression of GRIP1 enhanced CAR-mediated transactivation in cultured hepatic-derived cells 2-3-fold. In hepatocytes transfected in vivo, expression of exogenous GRIP1 alone induced transactivation of the CYP2B1 PB-dependent enhancer 15-fold, whereas CAR expression alone resulted in only a 3-fold enhancement in untreated mice. Remarkably, CAR and GRIP1 together synergistically transactivated the enhancer about 150-fold, which is approximately equal to activation by PB treatment. In PB-treated mice, expression of exogenous CAR alone had little effect, expression of GRIP1 increased transactivation about 2-fold, and with CAR and GRIP, a 4-fold activation was observed. In untreated mice, expression of GRIP resulted in nuclear translocation of green fluorescent protein-CAR. These results strongly suggest that a p160 coactivator functions in CAR-mediated transactivation in vivo in response to PB treatment and that the synergistic activation of CAR by GRIP in untreated animals results from both nuclear translocation and activation of CAR.
...
PMID:Glucocorticoid receptor-interacting protein 1 mediates ligand-independent nuclear translocation and activation of constitutive androstane receptor in vivo. 1200 Jul 48

Glucocorticoid-induced gene transcription has been shown to be mediated by coactivators bound to the glucocorticoid receptor (GR). The glucocorticoid antagonist RU486 interferes with the steroid-mediated activation and can also exhibit partial agonist activity, a response in which corepressors have been implicated. Here we have shown that deletion of the N terminus of GR totally abolishes the agonist activity of RU486. Furthermore, we have demonstrated that corepressors bind directly to the RU486-bound GR as determined by glutathione S-transferase pull-down, mammalian two-hybrid assay, and coimmunoprecipitation. Fine mapping of the interaction regions within GR and the corepressor NCoR reveals a complex interaction profile that involves a number of domains in each protein. Notably, the N and the C termini of GR are both involved in corepressor binding. Thus, the N terminus of GR is a major determinant for RU486-dependent NCoR interaction as well as for RU486-mediated agonist activity.
...
PMID:RU486-induced glucocorticoid receptor agonism is controlled by the receptor N terminus and by corepressor binding. 1201 Oct 91

The fragments of the androgen receptor (amino acids: 359-732) and of the glucocorticoid receptor (amino acids: 396-548) were expressed in E. coli as fusion proteins with GST. Both fusion proteins, denoted GST-AR and GST-GR, contained the DNA-binding domain and some flanking amino acids. In gel retardation assay both fusion proteins could bind the androgen/glucocorticoid response element (ARE/GRE). We found that both cytosol and nuclear extracts from rat ventral prostate (v.p), but not from other source tested could abolish the interaction of GST-AR and GST-GR with ARE/GRE (from C3 (1) gene and MMTV LTR). The inhibition was androgen-dependent and sensitive to temperature and trypsin treatment. It implies that a protein inhibitor was present in the rat ventral prostate.
...
PMID:A prostate-specific Protein Factor Inhibits the Interaction of Androgen Receptors with Hormone Response Elements. 1216 99

The trout glucocorticoid receptor (rtGR) contains an additional sequence of nine amino acids located between the two zinc fingers of the DNA-binding domain (DBD) (Endocrinology 136 (1995) 3774). Polymerase chain reaction on trout genomic DNA and sequencing were performed in the DBD region, demonstrating that this peptide is encoded by an additional exon of 27 nucleotides between the two exons encoding the two zinc fingers of other nuclear receptors. This additional sequence in the rtGR confers a better binding affinity of the receptor to a single GRE, as shown by gel shift experiments with GST-DBDrtGR fusion proteins, deleted or not of the nine amino acids (Delta9). This higher affinity is correlated with a higher constitutive transcriptional activity of the receptor on a reporter gene driven by a single GRE, but not with the ligand-induced transcriptional activity. Nevertheless, on a double GRE, the wild type and rtGR-Delta9 are equally active on both constitutive or dexamethasone-induced transcriptional activity. This original DBD structure could have emerged during evolution such as to allow better regulation of glucocorticoid dependent genes in relation to the large spectrum of cortisol physiological functions in fish.
...
PMID:Peptide insertion in the DNA-binding domain of fish glucocorticoid receptor is encoded by an additional exon and confers particular functional properties. 1224 33

A minimal system of five proteins, hsp90, hsp70, Hop, hsp40, and p23, assembles glucocorticoid receptor (GR).hsp90 heterocomplexes and causes the simultaneous opening of the steroid binding cleft to access by steroid. The first step in assembly is the ATP-dependent and hsp40 (YDJ-1)-dependent formation of a GR.hsp70 complex that primes the receptor for subsequent ATP-dependent activation by hsp90, Hop, and p23. This study focuses on three aspects of the GR priming reaction with hsp70. First, we have visualized the primed GR.hsp70 complexes by atomic force microscopy, and we find the most common stoichiometry to be 1:1, with some complexes of a size approximately 1:2 and a few complexes of larger size. Second, in a recent study of progesterone receptor priming, it was shown that hsp40 binds first, leading to the notion that it targets hsp70 to the receptor. We show here that hsp40 does not perform such a targeting function in priming the GR. Third, we focus on a short amino-terminal segment of the ligand binding domain that is required for GR.hsp90 heterocomplex assembly. By using two glutathione S-transferase (GST)/ligand binding domain fusions with (GST/520C) and without (GST/554C) hsp90 binding and steroid binding activity, we show that the priming step with hsp70 occurs with GST/554C, and it is the subsequent assembly step with hsp90 that is defective.
...
PMID:Visualization and mechanism of assembly of a glucocorticoid receptor.Hsp70 complex that is primed for subsequent Hsp90-dependent opening of the steroid binding cleft. 1280 78

BACKGROUND: Retinoic acid receptors (RARs) are ligand-regulated transcription factors controlling cellular proliferation and differentiation. Receptor-interacting proteins such as corepressors and coactivators play a crucial role in specifying the overall transcriptional activity of the receptor in response to ligand treatment. Little is known however on how receptor activity is controlled by intermediary factors which interact with RARs in a ligand-independent manner. RESULTS: We have identified the promyelocytic leukemia zinc finger protein (PLZF), a transcriptional corepressor, to be a RAR-interacting protein using the yeast two-hybrid assay. We confirmed this interaction by GST-pull down assays and show that the PLZF N-terminal zinc finger domain is necessary and sufficient for PLZF to bind RAR. The RAR ligand binding domain displayed the highest affinity for PLZF, but corepressor and coactivator binding interfaces did not contribute to PLZF recruitment. The interaction was ligand-independent and correlated to a decreased transcriptional activity of the RXR-RAR heterodimer upon overexpression of PLZF. A similar transcriptional interference could be observed with the estrogen receptor alpha and the glucocorticoid receptor. We further show that PLZF is likely to act by preventing RXR-RAR heterodimerization, both in-vitro and in intact cells. CONCLUSION: Thus RAR and PLZF interact physically and functionally. Intriguingly, these two transcription factors play a determining role in hematopoiesis and regionalization of the hindbrain and may, upon chromosomal translocation, form fusion proteins. Our observations therefore define a novel mechanism by which RARs activity may be controlled.
...
PMID:PLZF is a negative regulator of retinoic acid receptor transcriptional activity. 1452 15


<< Previous 1 2 3 4 5 Next >>

---