Nuclear receptors meta-pathway (WP2882)
Homo sapiens
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules. In response, these receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism. Nuclear receptors have the ability to directly bind to DNA and regulate the expression of adjacent genes, hence these receptors are classified as transcription factors. The regulation of gene expression by nuclear receptors generally only happens when a ligand is present. More specifically, ligand binding to a nuclear receptor results in a conformational change in the receptor, which, in turn, activates the receptor, resulting in up- or down-regulation of gene expression. A unique property of nuclear receptors that differentiates them from other classes of receptors is their ability to directly interact with and control the expression of genomic DNA. As a consequence, nuclear receptors play key roles in both embryonic development and adult homeostasis. Nuclear receptors may be classified according to either mechanism or homology. [From Wikipedia, the free encyclopedia]
Authors
Rianne Fijten , Egon Willighagen , Friederike Ehrhart , Martina Summer-Kutmon , Elisa Cirillo , Eric Weitz , Susan Coort , and Denise SlenterActivity
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Cited In
- Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor (2022).
- Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa (2022).
- Prognostic and Diagnostic Values of Semaphorin 5B and Its Correlation With Tumor-Infiltrating Immune Cells in Kidney Renal Clear-Cell Carcinoma (2022).
- Protein Phosphatase 1 Regulatory Subunit 3B Genotype at rs4240624 Has a Major Effect on Gallbladder Bile Composition (2020).
- Predictive models for stage and risk classification in head and neck squamous cell carcinoma (HNSCC) (2020).
- Biological Pathways Leading From ANGPTL8 to Diabetes Mellitus–A Co-expression Network Based Analysis (2018).
- Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Phenotype (2016).
- Systems biology approach reveals a common molecular basis for COVID-19 and non-alcoholic fatty liver disease (NAFLD) (2022).
- Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma (2022).
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
transcription factor mediated signaling pathway regulatory pathwayReferences
- The murine IL-2 promoter contains distal regulatory elements responsive to the Ah receptor, a member of the evolutionarily conserved bHLH-PAS transcription factor family. Jeon MS, Esser C. J Immunol. 2000 Dec 15;165(12):6975–83. PubMed Europe PMC Scholia
- The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Sugatani J, Kojima H, Ueda A, Kakizaki S, Yoshinari K, Gong QH, et al. Hepatology. 2001 May;33(5):1232–8. PubMed Europe PMC Scholia
- The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways. Cai Y, Konishi T, Han G, Campwala KH, French SW, Wan YJY. Eur J Pharm Sci. 2002 Feb;15(1):89–96. PubMed Europe PMC Scholia
- Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes. Drocourt L, Ourlin JC, Pascussi JM, Maurel P, Vilarem MJ. J Biol Chem. 2002 Jul 12;277(28):25125–32. PubMed Europe PMC Scholia
- PXR, CAR and drug metabolism. Willson TM, Kliewer SA. Nat Rev Drug Discov. 2002 Apr;1(4):259–66. PubMed Europe PMC Scholia
- The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Pascussi JM, Gerbal-Chaloin S, Drocourt L, Maurel P, Vilarem MJ. Biochim Biophys Acta. 2003 Feb 17;1619(3):243–53. PubMed Europe PMC Scholia
- Functional role of AhR in the expression of toxic effects by TCDD. Mimura J, Fujii-Kuriyama Y. Biochim Biophys Acta. 2003 Feb 17;1619(3):263–8. PubMed Europe PMC Scholia
- Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, et al. J Biol Chem. 2003 May 9;278(19):17277–83. PubMed Europe PMC Scholia
- Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor. Echchgadda I, Song CS, Roy AK, Chatterjee B. Mol Pharmacol. 2004 Mar;65(3):720–9. PubMed Europe PMC Scholia
- Peroxisome proliferator-activated receptor alpha target genes. Mandard S, Müller M, Kersten S. Cell Mol Life Sci. 2004 Feb;61(4):393–416. PubMed Europe PMC Scholia
- The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. Maglich JM, Watson J, McMillen PJ, Goodwin B, Willson TM, Moore JT. J Biol Chem. 2004 May 7;279(19):19832–8. PubMed Europe PMC Scholia
- Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Kodama S, Koike C, Negishi M, Yamamoto Y. Mol Cell Biol. 2004 Sep;24(18):7931–40. PubMed Europe PMC Scholia
- 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces insulin-like growth factor binding protein-1 gene expression and counteracts the negative effect of insulin. Marchand A, Tomkiewicz C, Marchandeau JP, Boitier E, Barouki R, Garlatti M. Mol Pharmacol. 2005 Feb;67(2):444–52. PubMed Europe PMC Scholia
- Chromatin immunoprecipitation (ChIP) scanning identifies primary glucocorticoid receptor target genes. Wang JC, Derynck MK, Nonaka DF, Khodabakhsh DB, Haqq C, Yamamoto KR. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15603–8. PubMed Europe PMC Scholia
- Mechanisms of glucocorticoid receptor signaling during inflammation. Smoak KA, Cidlowski JA. Mech Ageing Dev. 2004;125(10–11):697–706. PubMed Europe PMC Scholia
- Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Handschin C, Meyer UA. Arch Biochem Biophys. 2005 Jan 15;433(2):387–96. PubMed Europe PMC Scholia
- Subchronic exposure to TCDD, PeCDF, PCB126, and PCB153: effect on hepatic gene expression. Vezina CM, Walker NJ, Olson JR. Environ Health Perspect. 2004 Nov;112(16):1636–44. PubMed Europe PMC Scholia
- A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer. Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, et al. Mol Cell. 2004 Dec 22;16(6):919–28. PubMed Europe PMC Scholia
- TCDD induces c-jun expression via a novel Ah (dioxin) receptor-mediated p38-MAPK-dependent pathway. Weiss C, Faust D, Dürk H, Kolluri SK, Pelzer A, Schneider S, et al. Oncogene. 2005 Jul 21;24(31):4975–83. PubMed Europe PMC Scholia
- The GI-GPx gene is a target for Nrf2. Banning A, Deubel S, Kluth D, Zhou Z, Brigelius-Flohé R. Mol Cell Biol. 2005 Jun;25(12):4914–23. PubMed Europe PMC Scholia
- Over-production of IFN-gamma and IL-12 in AhR-null mice. Rodríguez-Sosa M, Elizondo G, López-Durán RM, Rivera I, Gonzalez FJ, Vega L. FEBS Lett. 2005 Nov 21;579(28):6403–10. PubMed Europe PMC Scholia
- Coordinate regulation of Phase I and II xenobiotic metabolisms by the Ah receptor and Nrf2. Köhle C, Bock KW. Biochem Pharmacol. 2007 Jun 15;73(12):1853–62. PubMed Europe PMC Scholia
- CAR and PXR: the xenobiotic-sensing receptors. Timsit YE, Negishi M. Steroids. 2007 Mar;72(3):231–46. PubMed Europe PMC Scholia
- The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4alpha in the regulation of human steroid-/bile acid-sulfotransferase. Echchgadda I, Song CS, Oh T, Ahmed M, De La Cruz IJ, Chatterjee B. Mol Endocrinol. 2007 Sep;21(9):2099–111. PubMed Europe PMC Scholia
- Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver. Gao H, Fält S, Sandelin A, Gustafsson JA, Dahlman-Wright K. Mol Endocrinol. 2008 Jan;22(1):10–22. PubMed Europe PMC Scholia
- AHR- and DNA-damage-mediated gene expression responses induced by benzo(a)pyrene in human cell lines. Hockley SL, Arlt VM, Brewer D, Te Poele R, Workman P, Giddings I, et al. Chem Res Toxicol. 2007 Dec;20(12):1797–810. PubMed Europe PMC Scholia
- TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A. Weiss C, Faust D, Schreck I, Ruff A, Farwerck T, Melenberg A, et al. Oncogene. 2008 Apr 3;27(15):2198–207. PubMed Europe PMC Scholia
- Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Pavek P, Dvorak Z. Curr Drug Metab. 2008 Feb;9(2):129–43. PubMed Europe PMC Scholia
- Mechanism of vitamin D receptor inhibition of cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes. Han S, Chiang JYL. Drug Metab Dispos. 2009 Mar;37(3):469–78. PubMed Europe PMC Scholia
- Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes. Hariparsad N, Chu X, Yabut J, Labhart P, Hartley DP, Dai X, et al. Nucleic Acids Res. 2009 Mar;37(4):1160–73. PubMed Europe PMC Scholia
- NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Hayes JD, McMahon M. Trends Biochem Sci. 2009 Apr;34(4):176–88. PubMed Europe PMC Scholia
- Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease. Gadaleta RM, van Mil SWC, Oldenburg B, Siersema PD, Klomp LWJ, van Erpecum KJ. Biochim Biophys Acta. 2010 Jul;1801(7):683–92. PubMed Europe PMC Scholia
- Involvement of aryl hydrocarbon receptor in basal and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced expression of target genes in primary human hepatocytes. Le Vee M, Jouan E, Fardel O. Toxicol In Vitro. 2010 Sep;24(6):1775–81. PubMed Europe PMC Scholia
- Estrogen receptors: therapies targeted to receptor subtypes. Nilsson S, Gustafsson JÅ. Clin Pharmacol Ther. 2011 Jan;89(1):44–55. PubMed Europe PMC Scholia
- Nrf2 target genes are induced under marginal selenium-deficiency. Müller M, Banning A, Brigelius-Flohé R, Kipp A. Genes Nutr. 2010 Dec;5(4):297–307. PubMed Europe PMC Scholia
- The aryl hydrocarbon receptor (AHR) transcription factor regulates megakaryocytic polyploidization. Lindsey S, Papoutsakis ET. Br J Haematol. 2011 Feb;152(4):469–84. PubMed Europe PMC Scholia
- From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Bock KW. Biochem Pharmacol. 2011 Jul 1;82(1):9–16. PubMed Europe PMC Scholia
- Crosstalk of thyroid hormone receptor and liver X receptor in lipid metabolism and beyond [Review]. Hashimoto K, Mori M. Endocr J. 2011;58(11):921–30. PubMed Europe PMC Scholia