Nr1i3

Summary

Gene Symbol: Nr1i3
Description: nuclear receptor subfamily 1, group I, member 3
Alias: AA209988, AI551208, CAR, CAR-beta, Care2, ESTM32, MB67, nuclear receptor subfamily 1 group I member 3, constitutive androstane receptor, constitutively transactivates RAREs, orphan nuclear receptor MB67
Species: mouse
Products:     Nr1i3

Top Publications

  1. Koike C, Moore R, Negishi M. Localization of the nuclear receptor CAR at the cell membrane of mouse liver. FEBS Lett. 2005;579:6733-6 pubmed
    The nuclear receptor constitutive active/androstane receptor CAR is a drug-sensing transcription factor...
  2. Tojima H, Kakizaki S, Yamazaki Y, Takizawa D, Horiguchi N, Sato K, et al. Ligand dependent hepatic gene expression profiles of nuclear receptors CAR and PXR. Toxicol Lett. 2012;212:288-97 pubmed publisher
    b>Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are key regulators of drug-metabolizing enzymes and transporters. These two receptors are closely associated with each other and also have overlapping functions...
  3. Wei P, Zhang J, Egan Hafley M, Liang S, Moore D. The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature. 2000;407:920-3 pubmed
    ..Here we show that the nuclear receptor CAR mediates the response evoked by a class of xenobiotics known as the 'phenobarbital-like inducers'...
  4. Saito K, Moore R, Negishi M. Nuclear receptor CAR specifically activates the two-pore K+ channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia. Toxicol Sci. 2013;132:151-61 pubmed publisher
    ..Upon activation by phenobarbital, nuclear receptor CAR binds the 97-bp response element (-2441/-2345) within the Kcnk1 promoter...
  5. Miao J, Fang S, Bae Y, Kemper J. Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1alpha. J Biol Chem. 2006;281:14537-46 pubmed
    The role of the constitutive androstane receptor (CAR) in xenobiotic metabolism by inducing expression of cytochromes P450 is well known, but CAR has also been implicated in the down-regulation of key genes involved in bile acid synthesis,..
  6. Yamamoto Y, Negishi M. The antiapoptotic factor growth arrest and DNA-damage-inducible 45 beta regulates the nuclear receptor constitutive active/androstane receptor-mediated transcription. Drug Metab Dispos. 2008;36:1189-93 pubmed publisher
    The nuclear receptor constitutive active/androstane receptor (CAR) up-regulated expression of the apoptotic growth arrest and DNA-damage-inducible 45 beta (GADD45B) gene in HepG2 cells...
  7. Guo D, Sarkar J, Suino Powell K, Xu Y, Matsumoto K, Jia Y, et al. Induction of nuclear translocation of constitutive androstane receptor by peroxisome proliferator-activated receptor alpha synthetic ligands in mouse liver. J Biol Chem. 2007;282:36766-76 pubmed
    ..PPARalpha ligands Wy-14,643, ciprofibrate, clofibrate, and others induce the nuclear translocation of constitutive androstane receptor (CAR) in mouse liver cells in vivo...
  8. Dong B, Saha P, Huang W, Chen W, Abu Elheiga L, Wakil S, et al. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A. 2009;106:18831-6 pubmed publisher
    b>Constitutive androstane receptor CAR (NR1I3) has been identified as a central mediator of coordinate responses to xenobiotic and endobiotic stress...
  9. Yamamoto Y, Moore R, Goldsworthy T, Negishi M, Maronpot R. The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. Cancer Res. 2004;64:7197-200 pubmed
    ..The nuclear receptor constitutive active/androstane receptor (CAR) is activated by PB as well as by various other xenobiotics such as therapeutic drugs and environmental pollutants...

More Information

Publications84

  1. 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;24:7931-40 pubmed
    The nuclear receptors CAR and PXR activate hepatic genes in response to therapeutic drugs and xenobiotics, leading to the induction of drug-metabolizing enzymes, such as cytochrome P450...
  2. Yamazaki Y, Kakizaki S, Horiguchi N, Sohara N, Sato K, Takagi H, et al. The role of the nuclear receptor constitutive androstane receptor in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2007;56:565-74 pubmed
    ..The pathological roles of the nuclear receptor constitutive androstane receptor (CAR), a key regulator of drug-metabolising enzymes, in the development of NASH were investigated...
  3. Koike C, Moore R, Negishi M. Extracellular signal-regulated kinase is an endogenous signal retaining the nuclear constitutive active/androstane receptor (CAR) in the cytoplasm of mouse primary hepatocytes. Mol Pharmacol. 2007;71:1217-21 pubmed
    The nuclear receptor constitutive active/androstane receptor (CAR) is sequestered in the cytoplasm of liver cells before its activation by therapeutic drugs and xenobiotics such as phenobarbital (PB) and 1,4-Bis[2-(3,5-dichloropyridyloxy)..
  4. Chen X, Meng Z, Wang X, Zeng S, Huang W. The nuclear receptor CAR modulates alcohol-induced liver injury. Lab Invest. 2011;91:1136-45 pubmed publisher
    The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily and a sensor and detoxifier of both xenobiotics and endobiotics...
  5. Min G, Kemper J, Kemper B. Glucocorticoid receptor-interacting protein 1 mediates ligand-independent nuclear translocation and activation of constitutive androstane receptor in vivo. J Biol Chem. 2002;277:26356-63 pubmed
    ..PB) induction of CYP2B genes is mediated by translocation of the constitutively active androstane receptor (CAR) to the nucleus...
  6. Blanco Bose W, Murphy M, Ehninger A, Offner S, Dubey C, Huang W, et al. C-Myc and its target FoxM1 are critical downstream effectors of constitutive androstane receptor (CAR) mediated direct liver hyperplasia. Hepatology. 2008;48:1302-11 pubmed publisher
    In the adult liver, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), an agonist of the constitutive androstane receptor (CAR, NR1I3), produces rapid hepatomegaly in the absence of injury...
  7. Swales K, Negishi M. CAR, driving into the future. Mol Endocrinol. 2004;18:1589-98 pubmed
    The nuclear orphan receptor CAR is active in the absence of ligand with the unique capability to be further regulated by activators. A number of these activators, including phenobarbital, do not directly bind to the receptor...
  8. Yamamoto Y, Kawamoto T, Negishi M. The role of the nuclear receptor CAR as a coordinate regulator of hepatic gene expression in defense against chemical toxicity. Arch Biochem Biophys. 2003;409:207-11 pubmed
    The nuclear receptor CAR (constitutive active receptor) mediates the induction of transcription of cytochrome P450 (CYP) genes by phenobarbital (PB) and PB-type inducers...
  9. Inoue K, Borchers C, Negishi M. Cohesin protein SMC1 represses the nuclear receptor CAR-mediated synergistic activation of a human P450 gene by xenobiotics. Biochem J. 2006;398:125-33 pubmed
    b>CAR (constitutive active/androstane receptor) regulates both the distal enhancer PBREM (phenobarbital-responsive enhancer module) and the proximal element OARE [OA (okadaic acid) response element] to synergistically up-regulate the ..
  10. Gao J, He J, Zhai Y, Wada T, Xie W. The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity. J Biol Chem. 2009;284:25984-92 pubmed publisher
    Obesity and type 2 diabetes are related metabolic disorders of high prevalence. The constitutive androstane receptor (CAR) was initially characterized as a xenobiotic receptor regulating the responses of mammals to xenotoxicants...
  11. Yamamoto Y, Moore R, Flavell R, Lu B, Negishi M. Nuclear receptor CAR represses TNFalpha-induced cell death by interacting with the anti-apoptotic GADD45B. PLoS ONE. 2010;5:e10121 pubmed publisher
    ..PB activates nuclear xenobiotic receptor Constitutive Active/Androstane Receptor (CAR; NR1I3) and this activation is shown to determine PB promotion of HCC in mice...
  12. Maglich J, Stoltz C, Goodwin B, Hawkins Brown D, Moore J, Kliewer S. Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol. 2002;62:638-46 pubmed
    The nuclear pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play central roles in protecting the body against environmental chemicals (xenobiotics)...
  13. Osabe M, Negishi M. Active ERK1/2 protein interacts with the phosphorylated nuclear constitutive active/androstane receptor (CAR; NR1I3), repressing dephosphorylation and sequestering CAR in the cytoplasm. J Biol Chem. 2011;286:35763-9 pubmed publisher
    The nuclear constitutive active/androstane receptor (CAR) is inactivated and sequestered in the cytoplasm when Thr-38 is phosphorylated...
  14. Mutoh S, Sobhany M, Moore R, Perera L, PEDERSEN L, Sueyoshi T, et al. Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling. Sci Signal. 2013;6:ra31 pubmed publisher
    ..nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver...
  15. Ueda A, Hamadeh H, Webb H, Yamamoto Y, Sueyoshi T, Afshari C, et al. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol. 2002;61:1-6 pubmed
    ..Although the nuclear orphan constitutive active receptor (CAR) has been identified as a key transcription factor that regulates the induction of CYP2B, the full scope of CAR-..
  16. Huang W, Zhang J, Washington M, Liu J, Parant J, Lozano G, et al. Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor. Mol Endocrinol. 2005;19:1646-53 pubmed
    The constitutive androstane receptor (CAR, NR1I3) is a central regulator of xenobiotic metabolism. CAR activation induces hepatic expression of detoxification enzymes and transporters and increases liver size...
  17. Hosseinpour F, Timsit Y, Koike C, Matsui K, Yamamoto Y, Moore R, et al. Overexpression of the Rho-guanine nucleotide exchange factor ECT2 inhibits nuclear translocation of nuclear receptor CAR in the mouse liver. FEBS Lett. 2007;581:4937-42 pubmed
    Various drugs such as phenobarbital (PB) trigger translocation of constitutive active/adrostane receptor (CAR) from the cytoplasm into the nucleus of mouse liver cells without directly binding to the receptor...
  18. Mutoh S, Osabe M, Inoue K, Moore R, PEDERSEN L, Perera L, et al. Dephosphorylation of threonine 38 is required for nuclear translocation and activation of human xenobiotic receptor CAR (NR1I3). J Biol Chem. 2009;284:34785-92 pubmed publisher
    Upon activation by therapeutics, the nuclear xenobiotic/ constitutive active/androstane receptor (CAR) regulates various liver functions ranging from drug metabolism and excretion to energy metabolism...
  19. Yoshinari K, Kobayashi K, Moore R, Kawamoto T, Negishi M. Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of protein phosphatase 2A in response to phenobarbital. FEBS Lett. 2003;548:17-20 pubmed
    The nuclear receptor CAR, a phenobarbital (PB)-responsive transcription factor, translocates into the nucleus of hepatocytes after PB induction...
  20. Zhang J, Huang W, Qatanani M, Evans R, Moore D. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J Biol Chem. 2004;279:49517-22 pubmed
    A double null mouse line (2XENKO) lacking the xenobiotic receptors CAR (constitutive androstane receptor) (NR1I3) and PXR (pregnane X receptor) (NR1I2) was generated to study their functions in response to potentially toxic xenobiotic and ..
  21. Choi H, Chung M, Tzameli I, Simha D, Lee Y, Seol W, et al. Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR. J Biol Chem. 1997;272:23565-71 pubmed
    ..nuclear hormone receptor superfamily, termed mCAR, that is closely related to the previously described human orphan MB67, referred to here as hCAR. Like hCAR, mCAR expression is highest in liver...
  22. Maglich J, Watson J, McMillen P, Goodwin B, Willson T, Moore J. The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. J Biol Chem. 2004;279:19832-8 pubmed
    The orphan nuclear receptor CAR (NR1I3) has been characterized as a central component in the coordinate response to xenobiotic and endobiotic stress...
  23. Johnson D, Li C, Chen L, Ghosh J, Chen J. Regulation and binding of pregnane X receptor by nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT). Mol Pharmacol. 2006;69:99-108 pubmed
    ..Taken together, our results suggest that the corepressor SMRT may bind to and regulate the transcriptional activity of PXR. ..
  24. Chen S, Wang K, Wan Y. Retinoids activate RXR/CAR-mediated pathway and induce CYP3A. Biochem Pharmacol. 2010;79:270-6 pubmed publisher
    ..In this study, a panel of retinoids and carotenoids was examined to determine their effects on activation of RXR/CAR-mediated pathway and regulation of CYP3A gene expression...
  25. Lickteig A, Csanaky I, Pratt Hyatt M, Klaassen C. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver. Toxicol Sci. 2016;151:403-18 pubmed publisher
    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury...
  26. Ross J, Plummer S, Rode A, Scheer N, Bower C, Vogel O, et al. Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo. Toxicol Sci. 2010;116:452-66 pubmed publisher
    ..The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice...
  27. Frank C, Molnár F, Matilainen M, Lempiäinen H, Carlberg C. Agonist-dependent and agonist-independent transactivations of the human constitutive androstane receptor are modulated by specific amino acid pairs. J Biol Chem. 2004;279:33558-66 pubmed
    The constitutive androstane receptor (CAR) is an interesting member of the nuclear receptor superfamily because of its exceptionally high constitutive activity due to ligand-independent interaction of the ligand-binding domain with co-..
  28. Maeda J, Inoue K, Ichimura R, Takahashi M, Kodama Y, Saito N, et al. Essential role of constitutive androstane receptor in Ginkgo biloba extract induced liver hypertrophy and hepatocarcinogenesis. Food Chem Toxicol. 2015;83:201-9 pubmed publisher
    ..the mode of action (MOA) for hepatocarcinogenesis by GBE, we investigated the involvement of the constitutive androstane receptor (CAR) in hepatocarcinogenesis induced by GBE using CAR-knockout (CARKO) and wild type (WT) mice...
  29. Qatanani M, Zhang J, Moore D. Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism. Endocrinology. 2005;146:995-1002 pubmed
    ..The xenobiotic receptor constitutive androstane receptor (CAR) (NR1I3) mediates the well-studied induction of CYP2B genes and other drug-metabolizing enzymes ..
  30. MacLeod A, McLaughlin L, Henderson C, Wolf C. Activation status of the pregnane X receptor influences vemurafenib availability in humanized mouse models. Cancer Res. 2015;75:4573-81 pubmed publisher
    ..Activation of PXR, but not of the closely related constitutive androstane receptor, profoundly reduced circulating levels of vemurafenib in humanized mice...
  31. Shizu R, Osabe M, Perera L, Moore R, Sueyoshi T, Negishi M. Phosphorylated Nuclear Receptor CAR Forms a Homodimer To Repress Its Constitutive Activity for Ligand Activation. Mol Cell Biol. 2017;37: pubmed publisher
    The nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and the development of diseases, including diabetes and tumors...
  32. Sueyoshi T, Green W, Vinal K, Woodrum T, Moore R, Negishi M. Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver. PLoS ONE. 2011;6:e21229 pubmed publisher
    ..Here we have utilized Car(+/+) and Car(-/-) mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the ..
  33. Kamino H, Yamazaki Y, Saito K, Takizawa D, Kakizaki S, Moore R, et al. Nuclear receptor CAR-regulated expression of the FAM84A gene during the development of mouse liver tumors. Int J Oncol. 2011;38:1511-20 pubmed publisher
    The nuclear xenobiotic receptor CAR is a phenobarbital (PB)-activated transcription factor...
  34. Beigneux A, Moser A, Shigenaga J, Grunfeld C, Feingold K. Reduction in cytochrome P-450 enzyme expression is associated with repression of CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse liver during the acute phase response. Biochem Biophys Res Commun. 2002;293:145-9 pubmed
    ..Nuclear hormone receptors CAR and PXR are key transactivators of Cyp2b and Cyp3a genes, respectively...
  35. Ueda A, Matsui K, Yamamoto Y, Pedersen L, Sueyoshi T, Negishi M. Thr176 regulates the activity of the mouse nuclear receptor CAR and is conserved in the NR1I subfamily members PXR and VDR. Biochem J. 2005;388:623-30 pubmed
    The mouse nuclear receptor CAR (constitutively active receptor) is a transcription factor that is activated by phenobarbital-type inducers such as TCPOBOP {1,4 bis[2-(3,5-dichloropyridyloxy)]benzene} in liver in vivo...
  36. Masuyama H, Nakatsukasa H, Hiramatsu Y. Effect of oncostatin M on uridine diphosphate-5'-glucuronosyltransferase 1A1 through cross talk with constitutive androstane receptor. Mol Endocrinol. 2010;24:745-53 pubmed publisher
    Hyperbilirubinemia remains a common condition in neonates. The constitutive androstane receptor (CAR) is an orphan nuclear receptor that has been shown to participate in the activation of the uridine diphosphate-5'-glucuronosyltransferase ..
  37. Choi E, Lee S, Yeom S, Kim G, Lee J, Kim S. Characterization of activating signal cointegrator-2 as a novel transcriptional coactivator of the xenobiotic nuclear receptor constitutive androstane receptor. Mol Endocrinol. 2005;19:1711-9 pubmed
    ..report, we demonstrate that ASC-2 also serves as a coactivator of the xenobiotic nuclear receptor constitutive androstane receptor (CAR)...
  38. Beilke L, Aleksunes L, Olson E, Besselsen D, Klaassen C, Dvorak K, et al. Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice. Toxicol Lett. 2009;188:38-44 pubmed publisher
    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR)...
  39. Miyata M, Shinno K, Kinoshita T, Kinoshita Y, Sugiura Y. Fish oil feeding reverses hepatomegaly and disrupted hepatic function due to the lack of FXR signaling. J Toxicol Sci. 2017;42:671-681 pubmed publisher
    ..These results suggest that fish oil feeding reverses hepatomegaly and disrupted hepatic function due to the lack of FXR signaling. ..
  40. Avouac J, Palumbo Zerr K, Ruzehaji N, Tomcik M, Zerr P, Dees C, et al. The nuclear receptor constitutive androstane receptor/NR1I3 enhances the profibrotic effects of transforming growth factor β and contributes to the development of experimental dermal fibrosis. Arthritis Rheumatol. 2014;66:3140-50 pubmed publisher
    ..This study was undertaken to investigate the effects of constitutive androstane receptor (CAR)/NR1I3, an orphan nuclear receptor, on fibroblast activation and experimental dermal fibrosis...
  41. Zhang Y, Lu H, Klaassen C. Expression of human CAR splicing variants in BAC-transgenic mice. Toxicol Sci. 2013;132:142-50 pubmed publisher
    The nuclear receptor constitutive androstane receptor (CAR) is a key regulator for drug metabolism in liver. Human CAR (hCAR) transcripts are subjected to alternative splicing...
  42. Slitt A, Cherrington N, Dieter M, Aleksunes L, Scheffer G, Huang W, et al. trans-Stilbene oxide induces expression of genes involved in metabolism and transport in mouse liver via CAR and Nrf2 transcription factors. Mol Pharmacol. 2006;69:1554-63 pubmed
    ..Phenobarbital increases Cyp2B expression in liver via activation of the constitutive androstane receptor (CAR)...
  43. Uppal H, Toma D, Saini S, Ren S, Jones T, Xie W. Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. Hepatology. 2005;41:168-76 pubmed
    ..The orphan nuclear receptors PXR and CAR have been proposed to play an important role in the detoxification of xeno- and endo-biotics by regulating the ..
  44. Stedman C, Liddle C, Coulter S, Sonoda J, Alvarez J, Moore D, et al. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proc Natl Acad Sci U S A. 2005;102:2063-8 pubmed
    Cholestasis is associated with accumulation of bile acids and lipids, and liver injury. The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic nuclear receptors that coordinate protective hepatic responses ..
  45. Roth A, Looser R, Kaufmann M, Blättler S, Rencurel F, Huang W, et al. Regulatory cross-talk between drug metabolism and lipid homeostasis: constitutive androstane receptor and pregnane X receptor increase Insig-1 expression. Mol Pharmacol. 2008;73:1282-9 pubmed publisher
    Activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) by xenobiotic inducers of cytochromes P450 is part of a pleiotropic response that includes liver hypertrophy, tumor promotion, effects on lipid homeostasis,..
  46. Hasegawa M, Kapelyukh Y, Tahara H, Seibler J, Rode A, Krueger S, et al. Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line. Mol Pharmacol. 2011;80:518-28 pubmed publisher
    ..a novel multiple humanized mouse line that combines a humanization for PXR, the closely related constitutive androstane receptor, and a replacement of the mouse Cyp3a cluster with a large human genomic region carrying CYP3A4 and ..
  47. Tamura K, Inoue K, Takahashi M, Matsuo S, Irie K, Kodama Y, et al. Involvement of constitutive androstane receptor in liver hypertrophy and liver tumor development induced by triazole fungicides. Food Chem Toxicol. 2015;78:86-95 pubmed publisher
    We clarified the involvement of constitutive androstane receptor (CAR) in triazole-induced liver hypertrophy and tumorigenesis using CAR-knockout (CARKO) mice...
  48. Yueh M, Taniguchi K, Chen S, Evans R, Hammock B, Karin M, et al. The commonly used antimicrobial additive triclosan is a liver tumor promoter. Proc Natl Acad Sci U S A. 2014;111:17200-5 pubmed publisher
    ..an array of nuclear xenobiotic receptors (XenoRs), we found that TCS activates the nuclear receptor constitutive androstane receptor (CAR) and, contrary to previous reports, has no significant effect on mouse peroxisome proliferation ..
  49. Yamamoto Y, Moore R, Hess H, Guo G, Gonzalez F, Korach K, et al. Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity. J Biol Chem. 2006;281:16625-31 pubmed
    ..including farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive active/androstane receptor (CAR) are important in maintaining bile acid homeostasis and protecting the liver from bile acid toxicity...
  50. Cheng X, Klaassen C. Perfluorocarboxylic acids induce cytochrome P450 enzymes in mouse liver through activation of PPAR-alpha and CAR transcription factors. Toxicol Sci. 2008;106:29-36 pubmed publisher
    ..5 mg/kg), but increased Cyp2B10 mRNA expression only at high doses (> 20 mg/kg). By using constitutive androstane receptor (CAR)-, pregnane-X receptor (PXR)-, peroxisome proliferator-activated receptor alpha (PPAR)-alpha-, ..
  51. Yarushkin A, Kazantseva Y, Prokopyeva E, Markova D, Pustylnyak Y, Pustylnyak V. Constitutive androstane receptor activation evokes the expression of glycolytic genes. Biochem Biophys Res Commun. 2016;478:1099-105 pubmed publisher
    It is well-known that constitutive androstane receptor (CAR) activation by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) increases the liver-to-body weight ratio...
  52. Boussadia B, Gangarossa G, Mselli Lakhal L, Rousset M, de Bock F, Lassere F, et al. Lack of CAR impacts neuronal function and cerebrovascular integrity in vivo. Exp Neurol. 2016;283:39-48 pubmed publisher
    ..Clinically, an association between the constitutive androstane NR (CAR) and cognitive impairment was proposed, however never experimentally investigated...
  53. Gonzalez M, Carlberg C. Cross-repression, a functional consequence of the physical interaction of non-liganded nuclear receptors and POU domain transcription factors. J Biol Chem. 2002;277:18501-9 pubmed
    ..In this study, the adopted orphan receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) were found to perform direct protein-protein interactions with ..
  54. Zhang J, Huang W, Chua S, Wei P, Moore D. Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science. 2002;298:422-4 pubmed
    We have identified the xenobiotic receptor CAR (constitutive androstane receptor) as a key regulator of acetaminophen metabolism and hepatotoxicity...
  55. Saini S, Sonoda J, Xu L, Toma D, Uppal H, Mu Y, et al. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol. 2004;65:292-300 pubmed
    ..In this study, using transgenic mice bearing conditional expression of the activated constitutive androstane receptor (CAR), we demonstrate that activation of CAR is both necessary and sufficient to confer resistance to ..
  56. Huang W, Zhang J, Wei P, Schrader W, Moore D. Meclizine is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for human CAR. Mol Endocrinol. 2004;18:2402-8 pubmed
    The constitutive androstane receptor (CAR, NR1I3) is a key regulator of xenobiotic and endobiotic metabolism...
  57. Luisier R, Lempiäinen H, Scherbichler N, Braeuning A, Geissler M, Dubost V, et al. Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors. Toxicol Sci. 2014;139:501-11 pubmed publisher
    The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic ..
  58. Numazawa S, Shindo S, Maruyama K, Chibana F, Kawahara Y, Ashino T, et al. Impaired nuclear translocation of CAR in hepatic preneoplastic lesions: association with an attenuated CYP2B induction by phenobarbital. FEBS Lett. 2005;579:3560-4 pubmed
    Phenobarbital (PB) induction of CYP2B, a representative target gene of constitutive androstane receptor (CAR), has been observed to be attenuated in preneoplastic lesions of rat liver; however, molecular basis for this attenuation is ..
  59. Stoner M, Auerbach S, Zamule S, Strom S, Omiecinski C. Transactivation of a DR-1 PPRE by a human constitutive androstane receptor variant expressed from internal protein translation start sites. Nucleic Acids Res. 2007;35:2177-90 pubmed
    Downstream in-frame start codons produce amino-terminal-truncated human constitutive androstane receptor protein isoforms (DeltaNCARs)...
  60. Sarkar J, Qi C, Guo D, Ahmed M, Jia Y, Usuda N, et al. Transcription coactivator PRIP, the peroxisome proliferator-activated receptor (PPAR)-interacting protein, is redundant for the function of nuclear receptors PParalpha and CAR, the constitutive androstane receptor, in mouse liver. Gene Expr. 2007;13:255-69 pubmed
    ..parenchymal cells (PBP(LIV-/-)) results in the near abrogation of the induction of PPARalpha and CAR (constitutive androstane receptor)-regulated genes in liver...
  61. Renga B, Migliorati M, Mencarelli A, Cipriani S, D Amore C, Distrutti E, et al. Farnesoid X receptor suppresses constitutive androstane receptor activity at the multidrug resistance protein-4 promoter. Biochim Biophys Acta. 2011;1809:157-65 pubmed publisher
    ..CITCO), an activator of constitutive androstane receptor (CAR)...
  62. Takizawa D, Kakizaki S, Horiguchi N, Yamazaki Y, Tojima H, Mori M. Constitutive active/androstane receptor promotes hepatocarcinogenesis in a mouse model of non-alcoholic steatohepatitis. Carcinogenesis. 2011;32:576-83 pubmed publisher
    The nuclear receptor constitutive active/androstane receptor (CAR) acts as a sensor of toxic byproducts derived from the endogenous metabolism and exogenous chemicals...
  63. Scheer N, Ross J, Rode A, Zevnik B, Niehaves S, Faust N, et al. A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response. J Clin Invest. 2008;118:3228-39 pubmed publisher
    The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are closely related orphan nuclear hormone receptors that play a critical role as xenobiotic sensors in mammals...
  64. Chen T, Chen Q, Xu Y, Zhou Q, Zhu J, Zhang H, et al. SRC-3 is required for CAR-regulated hepatocyte proliferation and drug metabolism. J Hepatol. 2012;56:210-7 pubmed publisher
    Nuclear receptors such as pregnane X receptor and constitutive androstane receptor (CAR) are important regulators of drug-metabolizing systems such as P450 enzymes and modulate xenobiotic metabolism as well as hepatocellular proliferation...
  65. Yamazaki Y, Moore R, Negishi M. Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver. Lab Invest. 2011;91:1624-33 pubmed publisher
    ..DDC) activates the nuclear receptor constitutive active/androstane receptor (CAR), resulting in proliferation of oval cells in mouse liver...
  66. Ohno M, Kanayama T, Moore R, Ray M, Negishi M. The roles of co-chaperone CCRP/DNAJC7 in Cyp2b10 gene activation and steatosis development in mouse livers. PLoS ONE. 2014;9:e115663 pubmed publisher
    Cytoplasmic constitutive active/androstane receptor (CAR) retention protein (CCRP and also known as DNAJC7) is a co-chaperone previously characterized to retain nuclear receptor CAR in the cytoplasm of HepG2 cells...
  67. Smetanina M, Pakharukova M, Kurinna S, Dong B, Hernandez J, Moore D, et al. Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes. Toxicol Appl Pharmacol. 2011;255:76-85 pubmed publisher
    ..Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT...
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    ..The constitutive androstane receptor (CAR) is a known xenobiotic receptor, which induces the detoxification and transport of bilirubin...
  69. Xia J, Kemper B. Subcellular trafficking signals of constitutive androstane receptor: evidence for a nuclear export signal in the DNA-binding domain. Drug Metab Dispos. 2007;35:1489-94 pubmed
    Translocation of constitutive androstane receptor (CAR) from the cytoplasm to the nucleus is induced by phenobarbital-like drugs...
  70. De Vries E, Lammers L, Achterbergh R, Klümpen H, Mathot R, Boelen A, et al. Fasting-Induced Changes in Hepatic P450 Mediated Drug Metabolism Are Largely Independent of the Constitutive Androstane Receptor CAR. PLoS ONE. 2016;11:e0159552 pubmed publisher
    ..The expression of P450 enzymes is partly regulated by the constitutive androstane receptor (CAR)...
  71. Waxman D. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys. 1999;369:11-23 pubmed
    ..Roles for three "orphan" nuclear receptor superfamily members, designated CAR, PXR, and PPAR, in respectively mediating the induction of hepatic P450s belonging to families CYP2, CYP3, and CYP4 ..
  72. Seol W, Choi H, Moore D. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science. 1996;272:1336-9 pubmed
    ..of the receptor superfamily, including retinoid receptors, the thyroid hormone receptor, and the orphan receptor MB67. SHP also interacted directly with these receptors in vitro...
  73. Cheng S, Zou M, Liu Q, Kuang J, Shen J, Pu S, et al. Activation of Constitutive Androstane Receptor Prevents Cholesterol Gallstone Formation. Am J Pathol. 2017;187:808-818 pubmed publisher
    ..Lithogenic hepatic bile secretion precedes the formation of cholesterol gallstones. Constitutive androstane receptor (CAR), a member of nuclear family, plays an important role in cholesterol and bile acid metabolism...
  74. Dong B, Lee J, Park Y, Yang F, Xu G, Huang W, et al. Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis. Nat Commun. 2015;6:5944 pubmed publisher
    ..hepatocytes proliferate upon acute activation of either β-catenin or the nuclear xenobiotic receptor CAR. These responses are strictly limited and are tightly linked, since β-catenin is activated in nearly all of the ..
  75. Cho H, Jung J, Park H, Yang J, Jung S, An J, et al. In vivo deletion of CAR resulted in high bone mass phenotypes in male mice. J Cell Physiol. 2014;229:561-71 pubmed publisher
    b>Constitutive androstane receptor (CAR) was originally identified as xenobiotic sensor that regulates the expression of cytochrome P450 genes...