p300 is involved in formation of the TBP–TFIIA-containing basal transcription complex, TAC

We have recently identified a novel basal transcription complex, TAC, that is present and active in embryonal carcinoma (EC) cells but not in other adult cells such as COS7. In the search for factors involved in TAC formation, we found that expression of the adenoviral 12S E1A oncoprotein abolishes TAC formation in EC cells. This effect of E1A depends on its N-terminal domain that is essential for cell differentiation and that targets the transcriptional coactivators p300 and PCAF. Expression of p300 lacking its major E1A interaction domain, CH3, restores TAC formation in the presence of E1A, in a bromodomain- and HAT domain-dependent manner. Consistently, the unprocessed TFIIAαβ precursor that is selectively assembled into TAC is acetylated preferentially compared with the processed subunits present in ‘free’ TFIIA. Intriguingly, expression of p300 in COS7 cells that do not contain detectable levels of TAC instigates formation of TAC from endogenous components. Our data suggest that p300 plays a role in formation of the TBP–TFIIA-containing basal transcription complex, TAC

Heat-induced degradation of overexpressed glucocorticoid receptor - Separate protective roles of hsp90 and hsp70

Journal URL: http://www.sciencedirect.com/science/journal/0960076

Subunit Composition of the Untransformed Glucocorticoid Receptor in the Cytosol and in the Cell

Journal URL: http://www3.interscience.wiley.com/journal/119877016/grouphome/home.htm

Cleavage and proteasome-mediated degradation of the basal transcription factor TFIIA

This is also available in PubMed Central at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514921&rendertype=abstractJournal URL: http://www.nature.com/emboj/index.htm

A new class of phytoestrogens: Evaluation of the estrogenic activity of deoxybenzoins

Journal URL: http://www.sciencedirect.com/science/journal/1074552

The brominated flame retardants TBECH and DPTE alter prostate growth, histology and gene expression patterns in the mouse

The brominated flame retardants (BFRs), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) bind to the androgen receptor (AR). in vitro bioassays have shown that TBECH is a potent androgen agonist while DPTE is a potent AR antagonist. Both TBECH and DPTE alter gene expression associated with AR regulation. However, it remains to be determined if TBECH and DPTE can affect the prostate. For this reason, we exposed CD1 mice to a 1:1 mixture of TBECH diastereomers α and β, a 1:1 mixture of γ and δ, and to DPTE, and tested their effects on prostate growth, histology and gene expression profiles. Castrated mice were used to study the androgenic effects of TBECHαβ and TBECHγδ while the antagonistic effects of DPTE were studied in non-castrated mice. We observed that testosterone and TBECHγδ increased body and prostate weights while TBECHαβ affected neither of them; and that DPTE had no effect on body weight but reduced prostate weight drastically. Histomorphometric analysis of the prostate revealed epithelial and glandular alterations in the TBECHγδ group comparable to those in testosterone group while alterations in the TBECHαβ group were less pronounced. DPTE displayed androgen antagonist activity reminiscent of castration. The transcription profile of the prostate was altered by castration and exposure to testosterone and to TBECHγδ reversed several of these changes. Testosterone and TBECHγδ also regulated the expression of several androgen responsive genes implicated in prostate growth and cancer. While DPTE resulted in a drastic reduction in prostate weight, it only affected a small number of genes. The results indicate that TBECHγδ and DPTE are of high human health concern as they may contribute to changes in prostate growth, histology and function

Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes

Glucocorticoid receptor (GR) exerts anti-inflammatory action in part by antagonizing proinflammatory transcription factors such as the nuclear factor kappa-b (NFKB). Here, we assess the crosstalk of activated GR and RELA (p65, major NFKB component) by global identification of their binding sites and target genes. We show that coactivation of GR and p65 alters the repertoire of regulated genes and results in their association with novel sites in a mutually dependent manner. These novel sites predominantly cluster with p65 target genes that are antagonized by activated GR and vice versa. Our data show that coactivation of GR and NFKB alters signaling pathways that are regulated by each factor separately and provide insight into the networks underlying the GR and NFKB crosstalk

Biological evaluation of isoflavonoids from Genista halacsyi using estrogen-target cells: Activities of glucosides compared to aglycones.

The purpose of this study was to evaluate the response of estrogen target cells to a series of isoflavone glucosides and aglycones from Genista halacsyi Heldr. The methanolic extract of aerial parts of this plant was processed using fast centrifugal partition chromatography, resulting in isolation of four archetypal isoflavones (genistein, daidzein, isoprunetin, 8-C-β-D-glucopyranosyl-genistein) and ten derivatives thereof. 7-O-β-D-glucopyranosyl-genistein and 7,4΄-di-O-β-D-glucopyranosyl-genistein were among the most abundant constituents of the isolate. All fourteen, except genistein, displayed low binding affinity for estrogen receptors (ER). Models of binding to ERα could account for the low binding affinity of monoglucosides. Genistein and its glucosides displayed full efficacy in inducing alkaline phosphatase (AlkP) in Ishikawa cells, proliferation of MCF-7 cells and ER-dependent gene expression in reporter cells at low concentrations (around 0.3 μM). ICI182,780 fully antagonized these effects. The AlkP-inducing efficacy of the fourteen isoflavonoids was more strongly correlated with their transcriptional efficacy through ERα. O-monoglucosides displayed higher area under the dose-response curve (AUC) of AlkP response relative to the AUC of ERα-transcriptional response compared to the respective aglycones. In addition, 7-O-β-D-glucopyranosyl-genistein and 7,4΄-di-O-β-D-glucopyranosyl-genistein displayed estradiol-like efficacy in promoting differentiation of MC3T3-E1 cells to osteoblasts, while genistein was not convincingly effective in this respect. Moreover, 7,4΄-di-O-β-D-glucopyranosyl-genistein suppressed lipopolysaccharide-induced tumor necrosis factor mRNA expression in RAW 264.7 cells, while 7-O-β-D-glucopyranosyl-genistein was not convincingly effective and genistein was ineffective. However, genistein and its O-glucosides were ineffective in inhibiting differentiation of RAW 264.7 cells to osteoclasts and in protecting glutamate-challenged HT22 hippocampal neurons from oxidative stress-induced cell death. These findings suggest that 7-O-β-D-glucopyranosyl-genistein and 7,4΄-di-O-β-D-glucopyranosyl-genistein display higher estrogen-like and/or anti-inflammatory activity compared to the aglycone. The possibility of using preparations rich in O-β-D-glucopyranosides of genistein to substitute for low-dose estrogen in formulations for menopausal symptoms is discussed

Engineered chimeric enzymes as tools for drug discovery: generating reliable bacterial screens for the detection, discovery, and assessment of estrogen receptor modulators

No description supplie