Nuclear receptors: Genomic and non-genomic effects converge

Ordóñez‐Morán, Paloma; Muñoz, Alberto

doi:10.4161/cc.8.11.8579

Cited by 100 publications

(60 citation statements)

References 61 publications

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“…Because ERRα-dependent transcriptional activity is required for viral replication, the host cell may sequester ERRα in the cytoplasm in an attempt to limit infection. Even though nuclear receptors are most notable for altering gene expression by directly binding to target DNA sequences, additional functions have been described (52,53). As such, it is also conceivable that cytoplasmic ERRα binds host and/or viral proteins to regulate aspects of infection.…”

Section: Discussionmentioning

confidence: 99%

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Hwang¹,

Purdy

Wu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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An shRNA-mediated screen of the 48 human nuclear receptor genes identified multiple candidates likely to influence the production of human cytomegalovirus in cultured human fibroblasts, including the estrogen-related receptor α (ERRα), an orphan nuclear receptor. The 50-kDa receptor and a 76-kDa variant were induced posttranscriptionally following infection. Genetic and pharmacological suppression of the receptor reduced viral RNA, protein, and DNA accumulation, as well as the yield of infectious progeny. In addition, RNAs encoding multiple metabolic enzymes, including enzymes sponsoring glycolysis (enolase 1, triosephosphate isomerase 1, and hexokinase 2), were reduced when the function of ERRα was inhibited in infected cells. Consistent with the effect on RNAs, a substantial number of metabolites, which are normally induced by infection, were either not increased or were increased to a reduced extent in the absence of normal ERRα activity. We conclude that ERRα is needed for the efficient production of cytomegalovirus progeny, and we propose that the nuclear receptor contributes importantly to the induction of a metabolic environment that supports optimal cytomegalovirus replication.herpesvirus | metabolism | nuclear receptor | mass spectrometry H uman cytomegalovirus (HCMV) belongs to the β-herpesvirus subfamily, and although most healthy individuals remain asymptomatic subsequent to infection, the pathogen is a major contributor to birth defects and to life-threatening disease in immunocompromised patients (1-3). As with all viruses, HCMV depends on the host cell to provide macromolecular building blocks for virion production, and throughout the course of its evolution, HCMV has adapted to manipulate numerous fundamental cellular processes, including RNA accumulation (4), translation (5), metabolism (6, 7), secretory pathways (8), and the cell cycle (9).The nuclear receptor gene family, of which there are 48 members in the human genome, encodes transcription factors (10). Some bind to specific hydrophobic ligands such as steroids, vitamin D, fatty acids, and lipids, providing a means to sense changes in the extracellular or intracellular environment; others are "orphans" with no known ligand, and are often constitutively active (11). As transcription factors that modulate broad gene regulatory networks, nuclear receptors control numerous physiological processes, including aspects of metabolism (cell autonomously and at the whole-organism level), development, and cellular differentiation, cancer, circadian rhythm, and immunity (11).The first indication that nuclear receptor signaling modulates HCMV replication surfaced after the identification of a retinoic acid response element within the major immediate-early promoter (MIEP) that caused a dose-dependent response to retinoic acid in reporter assays (12). Retinoic acid was further shown to enhance viral DNA replication and progeny production in human embryonal carcinoma cells and foreskin fibroblasts (13,14). The ligand also exacerbated symptoms of infection,...

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Section: Discussionmentioning

confidence: 99%

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Hwang¹,

Purdy

Wu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…ERs drive gene cascades comprising primary genes, whose transcription is directly controlled by the hormone through physical interaction of ERs with regulatory sites in the genome (genomic pathway of ER action) and/or with signal transduction effectors (nongenomic pathway), as well as downstream genes whose activity depends on the functions encoded by the primary responders. 5,6 The identification of primary estrogen target genes, and the downstream gene cascade that stems from them, is being actively pursued because it will provide essential information on the molecular and genomic pathways of the hormone-responsive BC phenotype. This is an important asset in clinical oncology because effective endocrine treatments of BC with ER␣ antagonists or aromatase inhibitors would be greatly improved by reliable predictors of tumor sensitivity to these drugs in the adjuvant or metastatic settings, as well as by the availability of markers of pharmacological resistance and new therapeutic targets to overcome it.…”

Section: Luminal-like Breast Tumor Cells Express Estrogen Receptor ␣ mentioning

confidence: 99%

Estrogen Receptor α Controls a Gene Network in Luminal-Like Breast Cancer Cells Comprising Multiple Transcription Factors and MicroRNAs

Cicatiello

Mutarelli

Grober

et al. 2010

The American Journal of Pathology

151

174

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“…17 Remarkably, at least part of these extranuclear signaling pathways converges and contributes to the control of gene transcription by VDR. 18,19 Moreover, 1,25(OH) 2 D 3 regulates genes that seem to lack VDR binding sites 15 and exerts posttranslational gene regulatory effects by controlling the expression of multiple proteases and protease inhibitors. 20 In addition, in certain systems, VDR has been found to interact with other transcription regulators, such as β-catenin and FoxO factors having ligand-dependent or -independent effects.…”

Section: Vitamin D Modulates the Expression Of Histone Demethylase Genesmentioning

confidence: 99%

Vitamin D has wide regulatory effects on histone demethylase genes

et al. 2012

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Nuclear receptors: Genomic and non-genomic effects converge

Cited by 100 publications

References 61 publications

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Estrogen Receptor α Controls a Gene Network in Luminal-Like Breast Cancer Cells Comprising Multiple Transcription Factors and MicroRNAs

Vitamin D has wide regulatory effects on histone demethylase genes

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