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Activation of xenobiotic receptors: driving into the nucleus

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Pages 409-426 | Published online: 29 Jan 2010

Bibliography

  • Sonoda J, Pei L, Evans RM. Nuclear receptors: decoding metabolic disease. FEBS Lett 2008;582(1):2-9
  • Tzameli I, Moore DD. Role reversal: new insights from new ligands for the xenobiotic receptor CAR. Trends Endocrinol Metab 2001;12(1):7-10
  • Nagy L, Schwabe JW. Mechanism of the nuclear receptor molecular switch. Trends Biochem Sci 2004;29(6):317-24
  • Petrick JS, Klaassen CD. Importance of hepatic induction of constitutive androstane receptor and other transcription factors that regulate xenobiotic metabolism and transport. Drug Metab Dispos 2007;35(10):1806-15
  • di Masi A, Marinis ED, Ascenzi P, Nuclear receptors CAR and PXR: molecular, functional, and biomedical aspects. Mol Aspects Med 2009;30(5):297-343
  • Burbach KM, Poland A, Bradfield CA. Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc Natl Acad Sci USA 1992;89(17):8185-9
  • Ikuta T, Eguchi H, Tachibana T, Nuclear localization and export signals of the human aryl hydrocarbon receptor. J Biol Chem 1998;273(5):2895-904
  • Kawamoto T, Sueyoshi T, Zelko I, Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol Cell Biol 1999;19(9):6318-22
  • Kawana K, Ikuta T, Kobayashi Y, Molecular mechanism of nuclear translocation of an orphan nuclear receptor, SXR. Mol Pharmacol 2003;63(3):524-31
  • Li H, Chen T, Cottrell J, Wang H. Nuclear translocation of Ad/EYFP-hCAR: a novel tool for screening human CAR activators in human primary hepatocytes. Drug Metab Dispos 2009;37(5):1098-106
  • Mohan R, Heyman RA. Orphan nuclear receptor modulators. Curr Top Med Chem 2003;3(14):1637-47
  • Olefsky JM. Nuclear receptor minireview series. J Biol Chem 2001;276(40):36863-4
  • Orans J, Teotico DG, Redinbo MR. The nuclear xenobiotic receptor pregnane X receptor: recent insights and new challenges. Mol Endocrinol 2005;19(12):2891-900
  • Watkins RE, Maglich JM, Moore LB, 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin. Biochemistry 2003;42(6):1430-8
  • Fischer U, Huber J, Boelens WC, The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 1995;82(3):475-83
  • Kaffman A, O'Shea EK. Regulation of nuclear localization: a key to a door. Annu Rev Cell Dev Biol 1999;15:291-339
  • Baes M, Gulick T, Choi HS, A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol 1994;14(3):1544-52
  • Choi HS, Chung M, Tzameli I, Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR. J Biol Chem 1997;272(38):23565-71
  • Yoshinari K, Sueyoshi T, Moore R, Nuclear receptor CAR as a regulatory factor for the sexually dimorphic induction of CYB2B1 gene by phenobarbital in rat livers. Mol Pharmacol 2001;59(2):278-84
  • Honkakoski P, Zelko I, Sueyoshi T, The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol Cell Biol 1998;18(10):5652-8
  • Kanno Y, Suzuki M, Nakahama T, Characterization of nuclear localization signals and cytoplasmic retention region in the nuclear receptor CAR. Biochim Biophys Acta 2005;1745(2):215-22
  • Forman BM, Tzameli I, Choi HS, Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta. Nature 1998;395(6702):612-5
  • Tzameli I, Pissios P, Schuetz EG, The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR. Mol Cell Biol 2000;20(9):2951-8
  • Maglich JM, Parks DJ, Moore LB, Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem 2003;278(19):17277-83
  • Wei P, Zhang J, Dowhan DH, Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response. Pharmacogenomics J 2002;2(2):117-26
  • Sueyoshi T, Moore R, Pascussi JM, Direct expression of fluorescent protein-tagged nuclear receptor CAR in mouse liver. Methods Enzymol 2002;357:205-13
  • Wang H, Faucette S, Moore R, Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin. J Biol Chem 2004;279(28):29295-301
  • Huang W, Zhang J, Wei P, Meclizine is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for human CAR. Mol Endocrinol 2004;18(10):2402-8
  • Huang W, Zhang J, Moore DD. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 2004;113(1):137-43
  • Burk O, Arnold KA, Nussler AK, Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol 2005;67(6):1954-65
  • Kobayashi K, Yamanaka Y, Iwazaki N, Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos 2005;33(7):924-9
  • Jyrkkarinne J, Windshugel B, Makinen J, Amino acids important for ligand specificity of the human constitutive androstane receptor. J Biol Chem 2005;280(7):5960-71
  • Faucette SR, Zhang TC, Moore R, Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. J Pharmacol Exp Ther 2007;320(1):72-80
  • Kublbeck J, Jyrkkarinne J, Poso A, Discovery of substituted sulfonamides and thiazolidin-4-one derivatives as agonists of human constitutive androstane receptor. Biochem Pharmacol 2008;76(10):1288-97
  • Wei P, Zhang J, Egan-Hafley M, The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 2000;407(6806):920-3
  • Kawamoto T, Kakizaki S, Yoshinari K, Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene. Mol Endocrinol 2000;14(11):1897-905
  • Zhang J, Huang W, Chua SS, Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science 2002;298(5592):422-4
  • Makinen J, Reinisalo M, Niemi K, Dual action of oestrogens on the mouse constitutive androstane receptor. Biochem J 2003;376(Pt 2):465-72
  • Huang W, Zhang J, Chua SS, Induction of bilirubin clearance by the constitutive androstane receptor (CAR). Proc Natl Acad Sci USA 2003;100(7):4156-61
  • Murray M, Fiala-Beer E, Sutton D. Upregulation of cytochromes P450 2B in rat liver by orphenadrine. Br J Pharmacol 2003;139(4):787-96
  • Jackson JP, Ferguson SS, Moore R, The constitutive active/androstane receptor regulates phenytoin induction of Cyp2c29. Mol Pharmacol 2004;65(6):1397-404
  • Pustylnyak VO, Gulyaeva LF, Lyakhovich VV. CAR expression and inducibility of CYP2B genes in liver of rats treated with PB-like inducers. Toxicology 2005;216(2-3):147-53
  • Slitt AL, Cherrington NJ, Fisher CD, Induction of genes for metabolism and transport by trans-stilbene oxide in livers of Sprague-Dawley and Wistar-Kyoto rats. Drug Metab Dispos 2006;34(7):1190-7
  • Fisher CD, Augustine LM, Maher JM, Induction of drug-metabolizing enzymes by garlic and allyl sulfide compounds via activation of constitutive androstane receptor and nuclear factor E2-related factor 2. Drug Metab Dispos 2007;35(6):995-1000
  • Merrell MD, Jackson JP, Augustine LM, The Nrf2 activator oltipraz also activates the constitutive androstane receptor. Drug Metab Dispos 2008;36(8):1716-21
  • Cheng X, Klaassen CD. Perfluorocarboxylic acids induce cytochrome P450 enzymes in mouse liver through activation of PPAR-alpha and CAR transcription factors. Toxicol Sci 2008;106(1):29-36
  • Moore LB, Parks DJ, Jones SA, Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J Biol Chem 2000;275(20):15122-7
  • Jyrkkarinne J, Makinen J, Gynther J, Molecular determinants of steroid inhibition for the mouse constitutive androstane receptor. J Med Chem 2003;46(22):4687-95
  • Li L, Chen T, Stanton JD, The peripheral benzodiazepine receptor ligand 1-(2-chlorophenyl-methylpropyl)-3-isoquinoline-carboxamide is a novel antagonist of human constitutive androstane receptor. Mol Pharmacol 2008;74(2):443-53
  • Marc N, Galisteo M, Lagadic-Gossmann D, Regulation of phenobarbital induction of the cytochrome P450 2b9/10 genes in primary mouse hepatocyte culture. Involvement of calcium- and cAMP-dependent pathways. Eur J Biochem 2000;267(4):963-70
  • Kakizaki S, Yamamoto Y, Ueda A, Phenobarbital induction of drug/steroid-metabolizing enzymes and nuclear receptor CAR. Biochim Biophys Acta 2003;1619(3):239-42
  • Ding X, Staudinger JL. The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter. J Pharmacol Exp Ther 2005;314(1):120-7
  • Guo D, Sarkar J, Suino-Powell K, Induction of nuclear translocation of constitutive androstane receptor by peroxisome proliferator-activated receptor alpha synthetic ligands in mouse liver. J Biol Chem 2007;282(50):36766-76
  • Zelko I, Sueyoshi T, Kawamoto T, The peptide near the C terminus regulates receptor CAR nuclear translocation induced by xenochemicals in mouse liver. Mol Cell Biol 2001;21(8):2838-46
  • Hache RJ, Tse R, Reich T, Nucleocytoplasmic trafficking of steroid-free glucocorticoid receptor. J Biol Chem 1999;274(3):1432-9
  • Rowlands JC, Gustafsson JA. Aryl hydrocarbon receptor-mediated signal transduction. Crit Rev Toxicol 1997;27(2):109-34
  • Kazlauskas A, Sundstrom S, Poellinger L, The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor. Mol Cell Biol 2001;21(7):2594-607
  • Tai PK, Albers MW, Chang H, Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex. Science 1992;256(5061):1315-8
  • Kobayashi K, Sueyoshi T, Inoue K, Cytoplasmic accumulation of the nuclear receptor CAR by a tetratricopeptide repeat protein in HepG2 cells. Mol Pharmacol 2003;64(5):1069-75
  • Sueyoshi T, Moore R, Sugatani J, PPP1R16A, the membrane subunit of protein phosphatase 1beta, signals nuclear translocation of the nuclear receptor constitutive active/androstane receptor. Mol Pharmacol 2008;73(4):1113-21
  • Yoshinari K, Kobayashi K, Moore R, Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of protein phosphatase 2A in response to phenobarbital. FEBS Lett 2003;548(1-3):17-20
  • Kanno Y, Suzuki M, Miyazaki Y, Difference in nucleocytoplasmic shuttling sequences of rat and human constitutive active/androstane receptor. Biochim Biophys Acta 2007;1773(6):934-44
  • Koike C, Moore R, Negishi M. Localization of the nuclear receptor CAR at the cell membrane of mouse liver. FEBS Lett 2005;579(30):6733-6
  • Min G, Kemper JK, Kemper B. Glucocorticoid receptor-interacting protein 1 mediates ligand-independent nuclear translocation and activation of constitutive androstane receptor in vivo. J Biol Chem 2002;277(29):26356-63
  • Guo D, Sarkar J, Ahmed MR, Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) but not PPAR-interacting protein (PRIP) is required for nuclear translocation of constitutive androstane receptor in mouse liver. Biochem Biophys Res Commun 2006;347(2):485-95
  • Moore LB, Maglich JM, McKee DD, Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors. Mol Endocrinol 2002;16(5):977-86
  • Ueda A, Hamadeh HK, Webb HK, Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol 2002;61(1):1-6
  • Xiong H, Yoshinari K, Brouwer KL, Role of constitutive androstane receptor in the in vivo induction of Mrp3 and CYP2B1/2 by phenobarbital. Drug Metab Dispos 2002;30(8):918-23
  • Xie W, Barwick JL, Downes M, Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 2000;406(6794):435-9
  • Barwick JL, Quattrochi LC, Mills AS, Trans-species gene transfer for analysis of glucocorticoid-inducible transcriptional activation of transiently expressed human CYP3A4 and rabbit CYP3A6 in primary cultures of adult rat and rabbit hepatocytes. Mol Pharmacol 1996;50(1):10-6
  • Arnold KA, Eichelbaum M, Burk O. Alternative splicing affects the function and tissue-specific expression of the human constitutive androstane receptor. Nucl Recept 2004;2(1):1
  • Auerbach SS, Ramsden R, Stoner MA, Alternatively spliced isoforms of the human constitutive androstane receptor. Nucleic Acids Res 2003;31(12):3194-207
  • Lamba JK, Lamba V, Yasuda K, Expression of constitutive androstane receptor splice variants in human tissues and their functional consequences. J Pharmacol Exp Ther 2004;311(2):811-21
  • Savkur RS, Wu Y, Bramlett KS, Alternative splicing within the ligand binding domain of the human constitutive androstane receptor. Mol Genet Metab 2003;80(1-2):216-26
  • Jinno H, Tanaka-Kagawa T, Hanioka N, Identification of novel alternative splice variants of human constitutive androstane receptor and characterization of their expression in the liver. Mol Pharmacol 2004;65(3):496-502
  • DeKeyser JG, Stagliano MC, Auerbach SS, Di(2-ethylhexyl) phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant CAR2. Mol Pharmacol 2009;75(5):1005-13
  • Auerbach SS, Stoner MA, Su S, Retinoid X receptor-alpha-dependent transactivation by a naturally occurring structural variant of human constitutive androstane receptor (NR1I3). Mol Pharmacol 2005;68(5):1239-53
  • Chen T, Tompkins LM, Li L, A single amino acid controls the functional switch of human constitutive androstane receptor (CAR) 1 to the xenobiotic-sensitive splicing variant CAR3. J Pharmacol Exp Ther 2010;332(1):106-15
  • Xie W, Barwick JL, Simon CM, Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev 2000;14(23):3014-23
  • Lehmann JM, McKee DD, Watson MA, The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 1998;102(5):1016-23
  • Faucette SR, Sueyoshi T, Smith CM, Differential regulation of hepatic CYP2B6 and CYP3A4 genes by constitutive androstane receptor but not pregnane X receptor. J Pharmacol Exp Ther 2006;317(3):1200-9
  • Roy P, Yu LJ, Crespi CL, Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos 1999;27(6):655-66
  • Schwartz PS, Chen CS, Waxman DJ. Sustained P450 expression and prodrug activation in bolus cyclophosphamide-treated cultured tumor cells. Impact of prodrug schedule on P450 gene-directed enzyme prodrug therapy. Cancer Gene Ther 2003;10(8):571-82
  • Xu RX, Lambert MH, Wisely BB, A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer. Mol Cell 2004;16(6):919-28
  • Sueyoshi T, Negishi M. Phenobarbital response elements of cytochrome P450 genes and nuclear receptors. Annu Rev Pharmacol Toxicol 2001;41:123-43
  • Kodama S, Negishi M. Phenobarbital confers its diverse effects by activating the orphan nuclear receptor car. Drug Metab Rev 2006;38(1-2):75-87
  • Hosseinpour F, Moore R, Negishi M, Serine 202 regulates the nuclear translocation of constitutive active/androstane receptor. Mol Pharmacol 2006;69(4):1095-102
  • Rencurel F, Foretz M, Kaufmann MR, Stimulation of AMP-activated protein kinase is essential for the induction of drug metabolizing enzymes by phenobarbital in human and mouse liver. Mol Pharmacol 2006;70(6):1925-34
  • Rencurel F, Stenhouse A, Hawley SA, AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line. J Biol Chem 2005;280(6):4367-73
  • Zelko I, Negishi M. Phenobarbital-elicited activation of nuclear receptor CAR in induction of cytochrome P450 genes. Biochem Biophys Res Commun 2000;277(1):1-6
  • Honkakoski P, Sueyoshi T, Negishi M. Drug-activated nuclear receptors CAR and PXR. Ann Med 2003;35(3):172-82
  • Suino K, Peng L, Reynolds R, The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization. Mol Cell 2004;16(6):893-905
  • Swales K, Kakizaki S, Yamamoto Y, Novel CAR-mediated mechanism for synergistic activation of two distinct elements within the human cytochrome P450 2B6 gene in HepG2 cells. J Biol Chem 2005;280(5):3458-66
  • Lempiainen H, Molnar F, Macias Gonzalez M, Antagonist- and inverse agonist-driven interactions of the vitamin D receptor and the constitutive androstane receptor with corepressor protein. Mol Endocrinol 2005;19(9):2258-72
  • Toell A, Kroncke KD, Kleinert H, Orphan nuclear receptor binding site in the human inducible nitric oxide synthase promoter mediates responsiveness to steroid and xenobiotic ligands. J Cell Biochem 2002;85(1):72-82
  • Simonsson US, Lindell M, Raffalli-Mathieu F, In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin. Eur J Clin Invest 2006;36(9):647-53
  • Bertilsson G, Heidrich J, Svensson K, Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 1998;95(21):12208-13
  • Blumberg B, Sabbagh W, Jr.Juguilon H, SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev 1998;12(20):3195-205
  • Kliewer SA, Moore JT, Wade L, An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 1998;92(1):73-82
  • Chang TK, Waxman DJ. Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Drug Metab Rev 2006;38(1-2):51-73
  • Teotico DG, Bischof JJ, Peng L, Structural basis of human pregnane X receptor activation by the hops constituent colupulone. Mol Pharmacol 2008;74(6):1512-20
  • Wada T, Gao J, Xie W. PXR and CAR in energy metabolism. Trends Endocrinol Metab 2009;20(6):273-9
  • Hariparsad N, Chu X, Yabut J, Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes. Nucleic Acids Res 2009;37(4):1160-73
  • Li T, Chiang JY. Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7 alpha-hydroxylase gene transcription. Am J Physiol Gastrointest Liver Physiol 2005;288(1):G74-84
  • Matic M, Nakhel S, Lehnert AM, A novel approach to investigate the subcellular distribution of nuclear receptors in vivo. Nucl Recept Signal 2009;7:e004
  • Squires EJ, Sueyoshi T, Negishi M. Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver. J Biol Chem 2004;279(47):49307-14
  • Lichti-Kaiser K, Brobst D, Xu C, A systematic analysis of predicted phosphorylation sites within the human pregnane X receptor protein. J Pharmacol Exp Ther 2009;331(1):65-76
  • Koyano S, Kurose K, Saito Y, Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab Dispos 2004;32(1):149-54
  • Saradhi M, Sengupta A, Mukhopadhyay G, Pregnane and Xenobiotic Receptor (PXR/SXR) resides predominantly in the nuclear compartment of the interphase cell and associates with the condensed chromosomes during mitosis. Biochim Biophys Acta 2005;1746(2):85-94
  • Takeshita A, Taguchi M, Koibuchi N, Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic receptor) in the mechanism of CYP3A4 inhibition by xenobiotics. J Biol Chem 2002;277(36):32453-8
  • Zhou C, Tabb MM, Sadatrafiei A, Tocotrienols activate the steroid and xenobiotic receptor, SXR, and selectively regulate expression of its target genes. Drug Metab Dispos 2004;32(10):1075-82
  • Ding X, Staudinger JL. Induction of drug metabolism by forskolin: the role of the pregnane X receptor and the protein kinase a signal transduction pathway. J Pharmacol Exp Ther 2005;312(2):849-56
  • Bhalla S, Ozalp C, Fang S, Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1alpha. Functional implications in hepatic cholesterol and glucose metabolism. J Biol Chem 2004;279(43):45139-47
  • Masuyama H, Suwaki N, Tateishi Y, The pregnane X receptor regulates gene expression in a ligand- and promoter-selective fashion. Mol Endocrinol 2005;19(5):1170-80
  • Chrencik JE, Orans J, Moore LB, Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin. Mol Endocrinol 2005;19(5):1125-34
  • Watkins RE, Wisely GB, Moore LB, The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 2001;292(5525):2329-33
  • Watkins RE, Noble SM, Redinbo MR. Structural insights into the promiscuity and function of the human pregnane X receptor. Curr Opin Drug Discov Devel 2002;5(1):150-8
  • Teotico DG, Frazier ML, Ding F, Active nuclear receptors exhibit highly correlated AF-2 domain motions. PLoS Comput Biol 2008;4(7):e1000111
  • Kliewer SA, Goodwin B, Willson TM. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 2002;23(5):687-702
  • Xie W, Yeuh MF, Radominska-Pandya A, Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci USA 2003;100(7):4150-5
  • Kast HR, Goodwin B, Tarr PT, Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem 2002;277(4):2908-15
  • Alnouti Y, Klaassen CD. Tissue distribution, ontogeny, and regulation of aldehyde dehydrogenase (Aldh) enzymes mRNA by prototypical microsomal enzyme inducers in mice. Toxicol Sci 2008;101(1):51-64
  • Gibson GG, Phillips A, Aouabdi S, Transcriptional regulation of the human pregnane-X receptor. Drug Metab Rev 2006;38(1-2):31-49
  • Wang H, Huang H, Li H, Activated pregnenolone X-receptor is a target for ketoconazole and its analogs. Clin Cancer Res 2007;13(8):2488-95
  • Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 2001;7(5):584-90
  • Wang H, Li H, Moore LB, The phytoestrogen coumestrol is a naturally occurring antagonist of the human pregnane X receptor. Mol Endocrinol 2008;22(4):838-57
  • Zhou C, Poulton EJ, Grun F, The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor. Mol Pharmacol 2007;71(1):220-9
  • Biswas A, Mani S, Redinbo MR, Elucidating the ‘Jekyll and Hyde’ nature of PXR: the case for discovering antagonists or allosteric antagonists. Pharm Res 2009;26(8):1807-15
  • Huang H, Wang H, Sinz M, Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole. Oncogene 2007;26(2):258-68
  • Das BC, Madhukumar AV, Anguiano J, Synthesis of novel ketoconazole derivatives as inhibitors of the human pregnane X Receptor (PXR; NR1I2; also termed SXR, PAR). Bioorg Med Chem Lett 2008;18(14):3974-7
  • Phelan D, Winter GM, Rogers WJ, Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch Biochem Biophys 1998;357(1):155-63
  • Quattrochi LC, Tukey RH. Nuclear uptake of the Ah (dioxin) receptor in response to omeprazole: transcriptional activation of the human CYP1A1 gene. Mol Pharmacol 1993;43(4):504-8
  • Ebert B, Seidel A, Lampen A. Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists. Carcinogenesis 2005;26(10):1754-63
  • Erichsen TJ, Ehmer U, Kalthoff S, Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene. Toxicol Appl Pharmacol 2008;230(2):252-60
  • Fujisawa-Sehara A, Sogawa K, Yamane M, Characterization of xenobiotic responsive elements upstream from the drug-metabolizing cytochrome P-450c gene: a similarity to glucocorticoid regulatory elements. Nucleic Acids Res 1987;15(10):4179-91
  • Lankisch TO, Gillman TC, Erichsen TJ, Aryl hydrocarbon receptor-mediated regulation of the human estrogen and bile acid UDP-glucuronosyltransferase 1A3 gene. Arch Toxicol 2008;82(9):573-82
  • Munzel PA, Schmohl S, Buckler F, Contribution of the Ah receptor to the phenolic antioxidant-mediated expression of human and rat UDP-glucuronosyltransferase UGT1A6 in Caco-2 and rat hepatoma 5L cells. Biochem Pharmacol 2003;66(5):841-7
  • Sugatani J, Kojima H, Ueda A, The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology 2001;33(5):1232-8
  • Zhang L, Savas U, Alexander DL, Characterization of the mouse Cyp1B1 gene. Identification of an enhancer region that directs aryl hydrocarbon receptor-mediated constitutive and induced expression. J Biol Chem 1998;273(9):5174-83
  • Lees MJ, Peet DJ, Whitelaw ML. Defining the role for XAP2 in stabilization of the dioxin receptor. J Biol Chem 2003;278(38):35878-88
  • Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 1995;35:307-40
  • Sogawa K, Fujii-Kuriyama Y. Ah receptor, a novel ligand-activated transcription factor. J Biochem 1997;122(6):1075-9
  • Ikuta T, Tachibana T, Watanabe J, Nucleocytoplasmic shuttling of the aryl hydrocarbon receptor. J Biochem 2000;127(3):503-9
  • Backlund M, Johansson I, Mkrtchian S, Signal transduction-mediated activation of the aryl hydrocarbon receptor in rat hepatoma H4IIE cells. J Biol Chem 1997;272(50):31755-63
  • Lesca P, Peryt B, Larrieu G, Evidence for the ligand-independent activation of the AH receptor. Biochem Biophys Res Commun 1995;209(2):474-82
  • Ikuta T, Kobayashi Y, Kawajiri K. Cell density regulates intracellular localization of aryl hydrocarbon receptor. J Biol Chem 2004;279(18):19209-16
  • Sadek CM, Allen-Hoffmann BL. Suspension-mediated induction of Hepa 1c1c7 Cyp1a-1 expression is dependent on the Ah receptor signal transduction pathway. J Biol Chem 1994;269(50):31505-9
  • Cho YC, Zheng W, Jefcoate CR. Disruption of cell-cell contact maximally but transiently activates AhR-mediated transcription in 10T1/2 fibroblasts. Toxicol Appl Pharmacol 2004;199(3):220-38
  • Yeager RL, Reisman SA, Aleksunes LM, Introducing the “TCDD-inducible AhR-Nrf2 gene battery”. Toxicol Sci 2009;111(2):238-46
  • Baba T, Mimura J, Nakamura N, Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. Mol Cell Biol 2005;25(22):10040-51
  • Kurose K, Tohkin M, Fukuhara M. A novel positive regulatory element that enhances hamster CYP2A8 gene expression mediated by xenobiotic responsive element. Mol Pharmacol 1999;55(2):279-87
  • Yueh MF, Huang YH, Hiller A, Involvement of the xenobiotic response element (XRE) in Ah receptor-mediated induction of human UDP-glucuronosyltransferase 1A1. J Biol Chem 2003;278(17):15001-6
  • Gerbal-Chaloin S, Pichard-Garcia L, Fabre JM, Role of CYP3A4 in the regulation of the aryl hydrocarbon receptor by omeprazole sulphide. Cell Signal 2006;18(5):740-50
  • Patel RD, Hollingshead BD, Omiecinski CJ, Aryl-hydrocarbon receptor activation regulates constitutive androstane receptor levels in murine and human liver. Hepatology 2007;46(1):209-18
  • Klinge CM, Kaur K, Swanson HI. The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1. Arch Biochem Biophys 2000;373(1):163-74

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