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Department of Endocrinology and Diabetes Mellitus, St Vincent’s University Hospital, Elm Park, Dublin, Ireland
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Department of Endocrinology and Diabetes Mellitus, St Vincent’s University Hospital, Elm Park, Dublin, Ireland
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Department of Endocrinology and Diabetes Mellitus, St Vincent’s University Hospital, Elm Park, Dublin, Ireland
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enzyme genes is the recruitment by nuclear receptors of coregulators (coactivators and corepressors) which interact with and effect transactivation ( McKenna et al. 1999 a ). It has been suggested that cofactors serve as a bridging apparatus between the
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et al . 2011 ). Primary coactivators interact directly with active TRs through the nuclear receptor (NR) recognition motif (NR box) ‘ LxxLL ’ ( Savkur & Burris 2004 ). This allows the recruitment of secondary coactivators to ultimately form a
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Introduction Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that were initially identified as targets of compounds that increase peroxisome proliferation. Three PPAR genes have been identified – NR1C1, NR1
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Estrogen signaling Estrogens exert their physiological effects through two estrogen receptor (ER) subtypes, ERα and ERβ that belong to the nuclear receptor family of ligand-activated transcription factors. ERα is mainly expressed in reproductive
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The orphan nuclear receptor TR2 and its truncated isoform deleted in the ligand binding domain (LBD) were localized exclusively in the nuclei as revealed by two methods of detection. An anti-hemagglutinin (HA) antibody detected specific nuclear localization of HA-tagged receptors and the green fluorescent protein (GFP)-tagged receptors were found to be distributed in the nuclei of living cells. By deletion analyses, the sequence responsible for targeting this receptor into the nucleus was defined. A stretch of 20 amino acid residues (KDCVINKHHRNRCQYCRLQR) within the second zinc-finger of this receptor is required for its nuclear localization and this signal is constitutively active. No nuclear localization signal was found in the N-terminus or the LBD. The GFP-tagged receptor remained biologically active, as evidenced by its repressive activity on the reporter that carried a binding site for this receptor, a direct repeat-5 (DR5). An electrophoretic mobility shift assay was performed to characterize the binding property of TR2 and its truncated isoform. TR2 bound to the DR5 as dimers whereas its truncated isoform bound as monomers.
Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France
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Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France
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potassium secretion in the distal tubule of the kidney, the colon, salivary and sweat glands via binding to the MR ( Pearce et al. 2003 ). The MR is a member of the steroid hormone receptor subgroup of the nuclear receptor superfamily ( Nuclear Receptor
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Cytokines and steroid hormones use different sets of signal transduction pathways, which seem to be unrelated. Interleukin-6 (IL-6) uses JAK tyrosine kinase and STAT (signal transducer and activator of transcription) transcription factor. Glucocorticoid binds glucocorticoid receptor (GR), which is a member of the steroid receptor superfamily. We have studied the crosstalk between the IL-6-JAK-STAT and glucocorticoid-nuclear receptor pathways. IL-6 and glucocorticoid synergistically activated the IL-6 response element on the rat alpha2-macroglobulin promoter (APRE)-driven luciferase gene. The exogenous expression of GR enhanced the synergism. The exogenous expression of dominant negative STAT3 completely abolished the IL-6 plus glucocorticoid-induced activation of the APRE-luciferase gene. Tyrosine phosphorylation of STAT3 stimulated by IL-6 alone was not different from that by IL-6 plus glucocorticoid. The protein level of STAT3 was also not increased by glucocorticoid stimulation. The time course of STAT3 tyrosine phosphorylation by IL-6 plus glucocorticoid was not different from that by IL-6 alone. The synergism was studied on the two other IL-6 response elements, the junB promoter (JRE-IL-6) and the interferon regulatory factor-1 (IRF-1) promoter (IRF-GAS) which could be activated by STAT3. The synergistic activation by glucocorticoid on the IL-6-activated JRE-IL-6 and the IRF-GAS-driven luciferase gene was not detected. Glucocorticoid did not change the mobility of IL-6-induced APRE-binding proteins in a gel shift assay. These results suggest that the synergism was through the GR and STAT3, and the coactivation pathway which was specific for APRE was the target of glucocorticoid.
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Introduction Estrogen (E) control of cell proliferation is a complex process that is subject to regulation at many levels. The nuclear receptor/transcription factor estrogen receptor-α (ESR1) is the key regulatory participant, transducing E action
Hudson Institute of Medical Research, Clayton, Australia
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of a protective role of ACE2 in the early stage of hypertension that is lost at later stages of disease ( Keidar et al. 2005 , 2007 ). Nuclear receptors other than MR, glucocorticoid receptor (GR) and oestrogen receptor (ER) can also regulate ACE2
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Houston Methodist Research Institute, College of Arts and Sciences, Departments of Paediatrics, Children's Health Research Institute, Department of Molecular Physiology and Biophysics, The Third Affiliated Hospital of Guangzhou Medical University, Genomic Medicine Program, 6670 Bertner Ave, Houston, Texas 77030, USA
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Houston Methodist Research Institute, College of Arts and Sciences, Departments of Paediatrics, Children's Health Research Institute, Department of Molecular Physiology and Biophysics, The Third Affiliated Hospital of Guangzhou Medical University, Genomic Medicine Program, 6670 Bertner Ave, Houston, Texas 77030, USA
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Thyroid hormone (TH) acts through specific receptors (TRs), which are conditional transcription factors, to induce fibroblast growth factor 21 (FGF21), a peptide hormone that is usually induced by fasting and that influences lipid and carbohydrate metabolism via local hepatic and systemic endocrine effects. While TH and FGF21 display overlapping actions when administered, including reductions in serum lipids, according to the current models these hormones act independently in vivo. In this study, we examined mechanisms of regulation of FGF21 expression by TH and tested the possibility that FGF21 is required for induction of hepatic TH-responsive genes. We confirm that active TH (triiodothyronine (T3)) and the TRβ-selective thyromimetic GC1 increase FGF21 transcript and peptide levels in mouse liver and that this effect requires TRβ. T3 also induces FGF21 in cultured hepatocytes and this effect involves direct actions of TRβ1, which binds a TRE within intron 2 of FGF21. Gene expression profiles of WT and Fgf21-knockout mice are very similar, indicating that FGF21 is dispensable for the majority of hepatic T3 gene responses. A small subset of genes displays diminished T3 response in the absence of FGF21. However, most of these are not obviously directly involved in T3-dependent hepatic metabolic processes. Consistent with these results, T3-dependent effects on serum cholesterol are maintained in the Fgf21 −/− background and we observe no effect of the Fgf21-knockout background on serum triglycerides and glucose. Our findings indicate that T3 regulates the genes involved in classical hepatic metabolic responses independently of FGF21.
