Interaction of glucocorticoid analogues with the human glucocorticoid receptor

Berger, T S; Parandoosh, Zahra; Perry, Bruce W.; Stein, Robert B.

doi:10.1016/0960-0760(92)90414-e

Cited by 79 publications

(57 citation statements)

References 10 publications

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“…To determine the efficiency of transfection and to standardize the expression of activity, a pRSV-␤-galactosidase expression plasmid was included in all cotransfections and analyzed as described previously (11,14). Each transfection was run in triplicate, and the average luciferase activity for the three independent transfections was normalized to the average ␤-galactosidase activity (average luciferase activity/(average ␤-galactosidase activity/min)).…”

Section: Methodsmentioning

confidence: 99%

“…Response element reporter plasmid constructions were generated by inserting synthetic oligonucleotides into the polylinker located 5Ј of the inducible thymidine kinase promoter in the previously described pBL luciferase vector (14). The integrity of all constructs was verified by DNA sequencing.…”

Section: Methodsmentioning

confidence: 99%

“…Mammalian cotransfections were performed essentially as described (11,14). Briefly, HepG2 cells, grown as a monolayer in Dulbecco's modified Eagle's medium containing 10% (v/v) fetal calf serum, were plated at 70% confluence 24 h prior to transfection.…”

Section: Methodsmentioning

confidence: 99%

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Tuberous Sclerosis Gene 2 Product Modulates Transcription Mediated by Steroid Hormone Receptor Family Members

Henry¹,

Yuan²,

Koszewski³

et al. 1998

Journal of Biological Chemistry

112

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Tuberous sclerosis (TSC) is a genetic disorder that results in the development of hamartomatous lesions in a variety of organ systems. Both the prevalence of the disease and the often devastating consequences of these tumors pose a serious health and medical care problem. The disease has been mapped to two distinct genetic loci in humans, and although the genes (TSC1 and TSC2) for both loci have recently been cloned, their function remains an enigma. Data presented here demonstrates that TSC2 protein can bind and selectively modulate transcription mediated by members of the steroid receptor superfamily of genes. These data place TSC2 into a growing list of nuclear receptor coregulators and strengthen the expanding body of evidence that these coregulators may play critical roles in cellular differentiation. Tuberous sclerosis (TSC)1 is an autosomal dominant neurocutaneous disorder associated with the development of hamartomatous lesions in a wide variety of tissues, including skin, kidney, brain, eye, lungs, and heart (1). The birth frequency has been estimated at approximately 1 in 6000 (2). Pathologically, TSC is classified as a disorder of cellular migration, proliferation, and differentiation. The tumors associated with TSC are diagnostically distinct, very seldom progress to malignancy, but often have very devastating consequences. The most classical are those that occur in the brain, where they frequently cause epilepsy, mental retardation, autism, and/or attention deficit disorders (1, 3). The relatively high prevalence and serious consequences of TSC make it an important health concern both here in the United States and throughout the world.TSC has been genetically linked to two loci in humans (4). About 60% of TSC cases are sporadic, but in families it has autodominant inheritance with high penetrance. TSC was first linked to chromosome 9q34 in 1987 (5), and this locus was termed TSC1. Later studies identified a second locus on chromosome 16p13 (6) that was called TSC2. The focal nature of TSC tumors suggests that TSC1 and TSC2 may function as tumor suppressor genes, and this is further supported by evidence for inactivating TSC2 germ line mutations and loss of heterozygosity at the TSC2 locus in TSC-associated tumors.The genes for both TSC1 and TSC2 have recently been cloned. Both were cloned by consortiums of investigators sequencing the specific regions of chromosome 9 (7) and chromosome 16 (8) to which TSC1 and TSC2 had been mapped, respectively. TSC1, or hemartin as it was named by the authors, encodes a cDNA of 8599 base pairs containing a 1164-amino acid open reading frame. TSC2, or tuberin, also encodes a rather large protein of 198 kilodaltons as specified by a cDNA of 5474 base pairs containing a 1784-amino acid open reading frame. The lack of any obvious structural similarities between TSC1 and TSC2 would suggest their relationship to tuberous sclerosis is either through some functional homology or through some converging function.Very little is known about the function of TSC1. The large TSC2...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Tuberous Sclerosis Gene 2 Product Modulates Transcription Mediated by Steroid Hormone Receptor Family Members

Henry¹,

Yuan²,

Koszewski³

et al. 1998

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

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“…Different volumes of supernatants were used to measure CAT activity (20 p.l; Seed and Sheen, 1988) or ,B-galactosidase activity (2 ,ul;Herbomel et al, 1984). Luciferase activity was measured as described in Berger et al (1992).…”

Section: Enzyme Assaysmentioning

confidence: 99%

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

Kitareewan

Burka

Tomer

et al. 1996

MBoC

179

135

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RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 ,uM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytenic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced[3H]-9cRA from RXR with Ki values of 4 ,uM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways.

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“…Co-transfection Assays-Transfections in CV-1 cells were performed as described (6,23). The reporter plasmid pPPREA3-tk-Luc containing three copies of the PPRE identified in the acyl CoA oxidase (AOX) gene has been described (24).…”

mentioning

confidence: 99%

Identification, Characterization, and Tissue Distribution of Human Peroxisome Proliferator-activated Receptor (PPAR) Isoforms PPARγ2 versus PPARγ1 and Activation with Retinoid X Receptor Agonists and Antagonists

Mukherjee¹,

Jow²,

Croston

et al. 1997

Journal of Biological Chemistry

385

258

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We describe the cloning, characterization, and tissue distribution of the two human peroxisome proliferator activated receptor isoforms hPPAR␥2 and hPPAR␥1. In cotransfection assays the two isoforms were activated to approximately the same extent by known PPAR␥ activators. Human PPAR␥ binds to DNA as a heterodimer with the retinoid X receptor (RXR). This heterodimer was activated by both RXR agonists and antagonists and the addition of PPAR␥ ligands with retinoids resulted in greater than additive activation. Such heterodimer-selective modulators may have a role in the treatment of PPAR␥/RXR-modulated diseases like diabetes. Northern blot analysis indicated the presence of PPAR␥ in skeletal muscle, and a sensitive RNase protection assay confirmed the presence of only PPAR␥1 in muscle that was not solely due to fat contamination. However, both PPAR␥1 and PPAR␥2 RNA were detected in fat, and the ratio of PPAR␥1 to PPAR␥2 RNA varied in different individuals. The presence of tissue-specific distribution of isoforms and the variable ratio of PPAR␥1 to PPAR␥2 raised the possibility that isoform expression may be modulated in disease states like non-insulin-dependent diabetes mellitus. Interestingly, a third protected band was detected with fat RNA indicating the possible existence of a third human PPAR␥ isoform.

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Interaction of glucocorticoid analogues with the human glucocorticoid receptor

Cited by 79 publications

References 10 publications

Tuberous Sclerosis Gene 2 Product Modulates Transcription Mediated by Steroid Hormone Receptor Family Members

Tuberous Sclerosis Gene 2 Product Modulates Transcription Mediated by Steroid Hormone Receptor Family Members

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

Identification, Characterization, and Tissue Distribution of Human Peroxisome Proliferator-activated Receptor (PPAR) Isoforms PPARγ2 versus PPARγ1 and Activation with Retinoid X Receptor Agonists and Antagonists

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