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 � a molecule that affects the receptor's behavior � 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. As discussed below, nuclear receptors may be classified according to either mechanism or homology.
Hayes JD, McMahon M; ''NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer.''; Trends Biochem Sci, 2009 PubMedEurope PMCScholia
Mueller M, Banning A, Brigelius-Flohé R, Kipp A; ''Nrf2 target genes are induced under marginal selenium-deficiency.''; Genes Nutr, 2010 PubMedEurope PMCScholia
Pavek P, Dvorak Z; ''Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues.''; Curr Drug Metab, 2008 PubMedEurope PMCScholia
Mandard S, Mueller M, Kersten S; ''Peroxisome proliferator-activated receptor alpha target genes.''; Cell Mol Life Sci, 2004 PubMedEurope PMCScholia
Echchgadda I, Song CS, Oh T, Ahmed M, De La Cruz IJ, Chatterjee B; ''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.''; Mol Endocrinol, 2007 PubMedEurope PMCScholia
Hockley SL, Arlt VM, Brewer D, Te Poele R, Workman P, Giddings I, Phillips DH; ''AHR- and DNA-damage-mediated gene expression responses induced by benzo(a)pyrene in human cell lines.''; Chem Res Toxicol, 2007 PubMedEurope PMCScholia
Gadaleta RM, van Mil SW, Oldenburg B, Siersema PD, Klomp LW, van Erpecum KJ; ''Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease.''; Biochim Biophys Acta, 2010 PubMedEurope PMCScholia
Hariparsad N, Chu X, Yabut J, Labhart P, Hartley DP, Dai X, Evers R; ''Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes.''; Nucleic Acids Res, 2009 PubMedEurope PMCScholia
Rodriguez-Sosa M, Elizondo G, Lopez-Duran RM, Rivera I, Gonzalez FJ, Vega L; ''Over-production of IFN-gamma and IL-12 in AhR-null mice.''; FEBS Lett, 2005 PubMedEurope PMCScholia
Drocourt L, Ourlin JC, Pascussi JM, Maurel P, Vilarem MJ; ''Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes.''; J Biol Chem, 2002 PubMedEurope PMCScholia
Sugatani J, Kojima H, Ueda A, Kakizaki S, Yoshinari K, Gong QH, Owens IS, Negishi M, Sueyoshi T; ''The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR.''; Hepatology, 2001 PubMedEurope PMCScholia
Willson TM, Kliewer SA; ''PXR, CAR and drug metabolism.''; Nat Rev Drug Discov, 2002 PubMedEurope PMCScholia
Echchgadda I, Song CS, Roy AK, Chatterjee B; ''Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor.''; Mol Pharmacol, 2004 PubMedEurope PMCScholia
Bock KW; ''From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans.''; Biochem Pharmacol, 2011 PubMedEurope PMCScholia
Jeon MS, Esser C; ''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.''; J Immunol, 2000 PubMedEurope PMCScholia
Gao H, Faelt S, Sandelin A, Gustafsson JA, Dahlman-Wright K; ''Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver.''; Mol Endocrinol, 2008 PubMedEurope PMCScholia
Koehle C, Bock KW; ''Coordinate regulation of Phase I and II xenobiotic metabolisms by the Ah receptor and Nrf2.''; Biochem Pharmacol, 2007 PubMedEurope PMCScholia
Marchand A, Tomkiewicz C, Marchandeau JP, Boitier E, Barouki R, Garlatti M; ''2,3,7,8-Tetrachlorodibenzo-p-dioxin induces insulin-like growth factor binding protein-1 gene expression and counteracts the negative effect of insulin.''; Mol Pharmacol, 2005 PubMedEurope PMCScholia
Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, Williams JD, Collins JL, Moore LB, Willson TM, Moore JT; ''A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer.''; Mol Cell, 2004 PubMedEurope PMCScholia
Handschin C, Meyer UA; ''Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.''; Arch Biochem Biophys, 2005 PubMedEurope PMCScholia
Tachibana K, Kobayashi Y, Tanaka T, Tagami M, Sugiyama A, Katayama T, Ueda C, Yamasaki D, Ishimoto K, Sumitomo M, Uchiyama Y, Kohro T, Sakai J, Hamakubo T, Kodama T, Doi T; ''Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms.''; Nucl Recept, 2005 PubMedEurope PMCScholia
Cai Y, Konishi T, Han G, Campwala KH, French SW, Wan YJ; ''The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways.''; Eur J Pharm Sci, 2002 PubMedEurope PMCScholia
Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, Stoltz CA, Kliewer SA, Lambert MH, Willson TM, Moore JT; ''Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes.''; J Biol Chem, 2003 PubMedEurope PMCScholia
Drocourt L, Ourlin JC, Pascussi JM, Maurel P, Vilarem MJ; ''Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes.''; J Biol Chem, 2002 PubMedEurope PMCScholia
Cai Y, Konishi T, Han G, Campwala KH, French SW, Wan YJ; ''The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways.''; Eur J Pharm Sci, 2002 PubMedEurope PMCScholia
Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, Stoltz CA, Kliewer SA, Lambert MH, Willson TM, Moore JT; ''Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes.''; J Biol Chem, 2003 PubMedEurope PMCScholia
Mandard S, Mueller M, Kersten S; ''Peroxisome proliferator-activated receptor alpha target genes.''; Cell Mol Life Sci, 2004 PubMedEurope PMCScholia
Weiss C, Faust D, Schreck I, Ruff A, Farwerck T, Melenberg A, Schneider S, Oesch-Bartlomowicz B, Zatloukalova J, Vondracek J, Oesch F, Dietrich C; ''TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A.''; Oncogene, 2008 PubMedEurope PMCScholia
Wang JC, Derynck MK, Nonaka DF, Khodabakhsh DB, Haqq C, Yamamoto KR; ''Chromatin immunoprecipitation (ChIP) scanning identifies primary glucocorticoid receptor target genes.''; Proc Natl Acad Sci U S A, 2004 PubMedEurope PMCScholia
Handschin C, Meyer UA; ''Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.''; Arch Biochem Biophys, 2005 PubMedEurope PMCScholia
Timsit YE, Negishi M; ''CAR and PXR: the xenobiotic-sensing receptors.''; Steroids, 2007 PubMedEurope PMCScholia
Vezina CM, Walker NJ, Olson JR; ''Subchronic exposure to TCDD, PeCDF, PCB126, and PCB153: effect on hepatic gene expression.''; Environ Health Perspect, 2004 PubMedEurope PMCScholia
Smoak KA, Cidlowski JA; ''Mechanisms of glucocorticoid receptor signaling during inflammation.''; Mech Ageing Dev, 2004 PubMedEurope PMCScholia
Li AC, Glass CK; ''PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis.''; J Lipid Res, 2004 PubMedEurope PMCScholia
Banning A, Deubel S, Kluth D, Zhou Z, Brigelius-Flohé R; ''The GI-GPx gene is a target for Nrf2.''; Mol Cell Biol, 2005 PubMedEurope PMCScholia
Handschin C, Meyer UA; ''Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.''; Arch Biochem Biophys, 2005 PubMedEurope PMCScholia
Mimura J, Fujii-Kuriyama Y; ''Functional role of AhR in the expression of toxic effects by TCDD.''; Biochim Biophys Acta, 2003 PubMedEurope PMCScholia
Han S, Chiang JY; ''Mechanism of vitamin D receptor inhibition of cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.''; Drug Metab Dispos, 2009 PubMedEurope PMCScholia
Pascussi JM, Gerbal-Chaloin S, Drocourt L, Maurel P, Vilarem MJ; ''The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors.''; Biochim Biophys Acta, 2003 PubMedEurope PMCScholia
Haarmann-Stemmann T, Bothe H, Abel J; ''Growth factors, cytokines and their receptors as downstream targets of arylhydrocarbon receptor (AhR) signaling pathways.''; Biochem Pharmacol, 2009 PubMedEurope PMCScholia
Kodama S, Koike C, Negishi M, Yamamoto Y; ''Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes.''; Mol Cell Biol, 2004 PubMedEurope PMCScholia
Maglich JM, Watson J, McMillen PJ, Goodwin B, Willson TM, Moore JT; ''The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction.''; J Biol Chem, 2004 PubMedEurope PMCScholia
Le Vee M, Jouan E, Fardel O; ''Involvement of aryl hydrocarbon receptor in basal and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced expression of target genes in primary human hepatocytes.''; Toxicol In Vitro, 2010 PubMedEurope PMCScholia
Hashimoto K, Mori M; ''Crosstalk of thyroid hormone receptor and liver X receptor in lipid metabolism and beyond [Review].''; Endocr J, 2011 PubMedEurope PMCScholia
Weiss C, Faust D, Duerk H, Kolluri SK, Pelzer A, Schneider S, Dietrich C, Oesch F, Goettlicher M; ''TCDD induces c-jun expression via a novel Ah (dioxin) receptor-mediated p38-MAPK-dependent pathway.''; Oncogene, 2005 PubMedEurope PMCScholia
Rochette-Egly C, Germain P; ''Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).''; Nucl Recept Signal, 2009 PubMedEurope PMCScholia
Gadaleta RM, van Mil SW, Oldenburg B, Siersema PD, Klomp LW, van Erpecum KJ; ''Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease.''; Biochim Biophys Acta, 2010 PubMedEurope PMCScholia
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