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Steroid hormone receptors are composed of six major functional domains, i.e. the A/B domains as the activation function 1 domain (AF-1), domain C as the DNA-binding domain, domain D as a hinge domain and domain E/F as the ligand-dependent transcriptional domain (AF-2). They regulate gene transcription through interactions with various nuclear factors of their domains, such as AF-1 and AF-2. We have...
Fatty acid amide hydrolase (FAAH) is a membrane-bound enzyme that inactivates a family of fatty acid amide molecules which are implicated in physiological processes such as pain and sleep. We cloned a 1.9 kb fragment of the 5′-untranslated region of the mouse FAAH gene into the pGL3 basic luciferase reporter vector and showed that this sequence has promoter activity in vitro. By primer extension analysis,...
We previously reported five DNA bend sites (ERB-4 to -1, and ERB+1) in the promoter region of the human estrogen receptor α (ERα) gene [FEBS Lett. 444 (1999) 117]. One of these sites, ERB-2, was accompanied by two half motifs of the estrogen response element (ERE) and several short poly(dA).poly(dT) tracts including an A4 tract located next to a half ERE motif. This A4 tract and the 20 bp immediate...
The human progesterone receptor (PgR) gene has a complex promoter that produces alternate mRNAs encoding the PgRA (94 kDa) and PgRB (120 kDa) protein isoforms. Expression of PgR is induced by estradiol (E 2 ) in the breast, reproductive tract and many cell lines despite the lack of a classical estrogen responsive element (ERE) in the promoter regions. We employed chromatin immunoprecipitation...
Proline-, glutamic acid- and leucine-rich protein 1 (PELP1)/modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptors (ERs; ERα and ERβ), modulates the genomic and nongenomic functions of the ERs. PELP1 expression is developmentally regulated in mammary glands and overexpressed in breast tumors. However, little is known about the regulation of PELP1. In...
We describe the development of a genetic, non-transcriptional assay for the detection of ligand binding to nuclear receptors based on the ligand-dependent reconstitution of the defective Ras/cAMP viability pathway of the Saccharomyces cerevisiae strain CDC25-2. We have characterized the assay using the estrogen receptor (ER) α as an example and found it to be extremely sensitive, stringent, rapid...
Nuclear receptor (NR) dependent transcriptional action requires recruitment of diverse factors characterized as coregulators. PNRC (proline-rich nuclear receptor coregulatory protein) is a member of coregulators that are capable of potentiating the transcriptional activity of NRs. Here we identified three human PNRC splicing variants designated PNRC1c, PNRC1d and PNRC1f. PNRC1c and PNRC1f are generated...
Osteoblasts are controlled by the individual and combined effects of systemic and local growth regulators. Here we show functional and physical interactions between estradiol (17βE) and Wnt activated pathways in osteoblasts. 17βE increased gene promoter activity by the Wnt pathway transcriptional effector T cell factor (TCF) in an estrogen receptor (ER) dependent way. This occurred independently of...
Estrogen actions are mainly mediated by specific nuclear estrogen receptors (ERs), for which different genes and a diversity of transcript variants have been identified, mainly in mammals. In this study, we investigated the presence of ER splice variants in the teleost fish gilthead sea bream (Sparus auratus), by comparison with the genomic organization of the related species Takifugu rubripes. Two...
Ribosome biogenesis is a fundamental cellular process intimately linked to cell growth and proliferation, which is upregulated in most of cancers especially in aggressive cancers. In breast and prostate cancers steroid hormone receptor signalling is the principal stimulus for cancer growth and progression. Here we investigated the link between estrogen and androgen receptor signalling and the initial...
Estrogen is one of the steroid hormones essential for skeletal development. The estrogen receptor (ER) is a transcription factor and a member of the steroid receptor superfamily. There are two different forms of the ER, usually referred to as α and β, each encoded by a separate gene. Hormone-activated ERs form dimers, since the two forms are coexpressed in many cell types. Bone sialoprotein (BSP)...
Mollusks have received increasing interest in ecotoxicological studies but so far the available scientific analyses of how their genes are affected by anthropogenic pollutants are scarce. The focus of this study is to identify an estrogen receptor (er) gene in the common prosobranch snail Bithynia tentaculata and to test a hypothesis that 17α-Ethinylestradiol (EE2) will modulate er gene expression...
Toll-like receptor 7 (TLR7) senses hepatitis C virus (HCV) infection and drives the host specific innate and adaptive immune response. The aim of this study was to estimate the distributions of TLR7 single nucleotide polymorphisms (SNPs), including rs179019 and rs3853839, as well as the effect of TLR7 gene variants on TLR7 mRNA expression and cytokine production in response to TLR7 agonist in vitro...
The 17α-ethinylestradiol (EE2), which could induce estrogenic effects, is found in different aquatic systems. The current study aimed to assess in vivo effects of short-term EE2 exposure on the transcriptional activity of genes in the brain and gonad tissues in order to characterize the mode of action of EE2 on the hypothalamus–pituitary–gonad axis in rare minnow (Gobiocypris rarus). The full length...
Status of DNA methylation is one of the most common molecular alterations in human neoplasia. Because it is possible to detect these epigenetic alterations in the bloodstream of patients, we investigated the aberrant DNA methylation status of estrogen receptor alpha (ERα) in patient pretherapeutic sera and tissue.In this case control study the patient series consisted of 120 sporadic primary breast...
Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors. Notably, the PELP1 protein has a histone-binding domain, recognizes histone modifications and interacts with several chromatin-modifying complexes. PELP1 serves as a substrate of multitude of kinases, and phosphorylation regulates...
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