Constitutive androstane receptor pathway (Homo sapiens)

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4, 29, 40TranscriptionLigandOtherMulti-drug resistanceDrug and steroid metabolismPhase 2 metabolismHSP90AA1NR1I3RXRAPPP2R4NR1I32, 26LigandHSP90AA1GenesTATA boxPBREMRXRANR1I3LigandDNAJC7DNAJC7NCOA6SP1NCOA1PPARGC1ANCOA2SMC1ACoregulatorsCAR target genesCYP2C9126ABCB1UGT1A11143ABCC236CYP2A611CYP4A1136CYP2C19SULT1A1618GSTA2CYP3A5116SULT2A1CYP3A476ALAS111EHHADHCYP2B6366ABCC336UGT1A4UGT1A68UGT1A98UGT1A388FOXO110


Description

The Constitutive Androstane Receptor (CAR) is a nuclear receptor and functions as a sensor for xenobiotics. It regulates transcription of genes encoding proteins in metabolism and excretion of xenobiotics. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Bibliography

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  3. 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 PubMed Europe PMC Scholia
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  7. 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 PubMed Europe PMC Scholia
  8. 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 PubMed Europe PMC Scholia
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  10. 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 PubMed Europe PMC Scholia
  11. 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 PubMed Europe PMC Scholia
  12. 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 PubMed Europe PMC Scholia
  13. Hashimoto K, Mori M; ''Crosstalk of thyroid hormone receptor and liver X receptor in lipid metabolism and beyond [Review].''; Endocr J, 2011 PubMed Europe PMC Scholia
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  15. 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 PubMed Europe PMC Scholia
  16. Rodríguez-Sosa M, Elizondo G, López-Durán RM, Rivera I, Gonzalez FJ, Vega L; ''Over-production of IFN-gamma and IL-12 in AhR-null mice.''; FEBS Lett, 2005 PubMed Europe PMC Scholia
  17. 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 PubMed Europe PMC Scholia
  18. 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 PubMed Europe PMC Scholia
  19. Nilsson S, Gustafsson JÅ; ''Estrogen receptors: therapies targeted to receptor subtypes.''; Clin Pharmacol Ther, 2011 PubMed Europe PMC Scholia
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  21. 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 PubMed Europe PMC Scholia
  22. Lindsey S, Papoutsakis ET; ''The aryl hydrocarbon receptor (AHR) transcription factor regulates megakaryocytic polyploidization.''; Br J Haematol, 2011 PubMed Europe PMC Scholia
  23. 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 PubMed Europe PMC Scholia
  24. 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 PubMed Europe PMC Scholia
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  26. 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 PubMed Europe PMC Scholia
  27. Mimura J, Fujii-Kuriyama Y; ''Functional role of AhR in the expression of toxic effects by TCDD.''; Biochim Biophys Acta, 2003 PubMed Europe PMC Scholia
  28. 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 PubMed Europe PMC Scholia
  29. Willson TM, Kliewer SA; ''PXR, CAR and drug metabolism.''; Nat Rev Drug Discov, 2002 PubMed Europe PMC Scholia
  30. 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 PubMed Europe PMC Scholia
  31. 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 PubMed Europe PMC Scholia
  32. 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 PubMed Europe PMC Scholia
  33. Han S, Chiang JY; ''Mechanism of vitamin D receptor inhibition of cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.''; Drug Metab Dispos, 2009 PubMed Europe PMC Scholia
  34. 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 PubMed Europe PMC Scholia
  35. Rochette-Egly C, Germain P; ''Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).''; Nucl Recept Signal, 2009 PubMed Europe PMC Scholia
  36. Handschin C, Meyer UA; ''Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR.''; Arch Biochem Biophys, 2005 PubMed Europe PMC Scholia
  37. Mandard S, Müller M, Kersten S; ''Peroxisome proliferator-activated receptor alpha target genes.''; Cell Mol Life Sci, 2004 PubMed Europe PMC Scholia
  38. 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 PubMed Europe PMC Scholia
  39. Rowlands JC, Gustafsson JA; ''Aryl hydrocarbon receptor-mediated signal transduction.''; Crit Rev Toxicol, 1997 PubMed Europe PMC Scholia
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  41. 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 PubMed Europe PMC Scholia
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  43. 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 PubMed Europe PMC Scholia
  44. Li AC, Glass CK; ''PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis.''; J Lipid Res, 2004 PubMed Europe PMC Scholia
  45. 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 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
117690view12:10, 22 May 2021EweitzModified title
106366view23:05, 22 August 2019KhanspersModified description
105560view06:17, 9 August 2019Khanspersremoved empty comment
105559view06:17, 9 August 2019KhanspersModified description
94791view23:01, 5 October 2017AlexanderPicoConverted lines
94781view22:25, 5 October 2017AlexanderPicoConverted lines and reconnected interactions
94724view14:29, 5 October 2017EgonwAdded mim-type annotation.
89203view04:03, 23 August 2016AriuttaOntology Term : 'signaling pathway' added !
79890view13:38, 23 April 2015Mkutmonresolved issues with some of the publication references
79889view13:32, 23 April 2015Mkutmonresolved issues with some of the publication references
79888view13:24, 23 April 2015Mkutmonremove unused publication xref
79887view13:23, 23 April 2015Mkutmonremoved redundant publication xref (pubmed: 15581595)
79600view05:49, 27 March 2015EgonwUpdated the Ensembl data source.
79540view15:02, 24 March 2015RiannefijtenModified description
79539view15:00, 24 March 2015Riannefijtenchanged pathway nodes to labels
79538view14:59, 24 March 2015Riannefijtenfixed unconnected lines, added reference
79495view13:39, 23 March 2015FehrhartUpdate of Gen IDs and comments
79480view12:57, 23 March 2015EgonwAnnotated "ligand" with the ChEBI identifier for 'androstane receptor agonist'.
78537view10:30, 7 January 2015MaintBotadded missing graphIds
78256view22:15, 17 December 2014KhanspersModified title
78216view15:05, 14 December 2014MaintBotModified title
78215view15:05, 14 December 2014EgonwUpdated GPML schema.
78088view11:37, 2 December 2014RiannefijtenNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABCB1GeneProduct5243 (Entrez Gene) ATP-binding cassette, sub-family B (MDR/TAP), member 1
ABCC2GeneProduct1244 (Entrez Gene) ATP-binding cassette, sub-family C (CFTR/MRP), member 2
ABCC3GeneProduct8714 (Entrez Gene) ATP-binding cassette, sub-family C (CFTR/MRP), member 3
ALAS1GeneProductENSG00000023330 (Ensembl)
CYP2A6GeneProduct1548 (Entrez Gene) cytochrome P450, family 2, subfamily A, polypeptide 6
CYP2B6GeneProduct1555 (Entrez Gene) cytochrome P450, family 2, subfamily B, polypeptide 6
CYP2C19GeneProduct1557 (Entrez Gene) cytochrome P450, family 2, subfamily C, polypeptide 19
CYP2C9GeneProduct1559 (Entrez Gene) cytochrome P450, family 2, subfamily C, polypeptide 9
CYP3A4GeneProduct1576 (Entrez Gene) cytochrome P450, family 3, subfamily A, polypeptide 4
CYP3A5GeneProduct1577 (Entrez Gene) cytochrome P450, family 3, subfamily A, polypeptide 5
CYP4A11GeneProductENSG00000187048 (Ensembl)
DNAJC7GeneProduct7266 (Entrez Gene) DnaJ (Hsp40) homolog, subfamily C, member 7
EHHADHGeneProductENSG00000113790 (Ensembl)
FOXO1GeneProductENSG00000150907 (Ensembl)
GSTA2GeneProduct2939 (Entrez Gene) glutathione S-transferase alpha 2
HSP90AA1GeneProduct3320 (Entrez Gene) heat shock protein 90kDa alpha (cytosolic), class A member 1
LigandMetaboliteCHEBI:77326 (ChEBI)
NCOA1GeneProduct8648 (Entrez Gene) nuclear receptor coactivator 1
NCOA2GeneProduct10499 (Entrez Gene) nuclear receptor coactivator 2
NCOA6GeneProduct23054 (Entrez Gene) nuclear receptor coactivator 6
NR1I3GeneProduct9970 (Entrez Gene) nuclear receptor subfamily 1, group I, member 3
PPARGC1AGeneProduct10891 (Entrez Gene) peroxisome proliferator-activated receptor gamma, coactivator 1 alpha
PPP2R4GeneProductENSG00000119383 (Ensembl) plays a role in translocation of CAR
RXRAGeneProduct6256 (Entrez Gene) retinoid X receptor, alpha
SMC1AGeneProduct8243 (Entrez Gene) structural maintenance of chromosomes 1A
SP1GeneProduct6667 (Entrez Gene) Sp1 transcription factor
SULT1A1GeneProductENSG00000196502 (Ensembl) during fasting
SULT2A1GeneProductENSG00000105398 (Ensembl)
UGT1A1GeneProductENSG00000241635 (Ensembl)
UGT1A3GeneProductENSG00000243135 (Ensembl)
UGT1A4GeneProductENSG00000244474 (Ensembl)
UGT1A6GeneProductENSG00000167165 (Ensembl)
UGT1A9GeneProductENSG00000241119 (Ensembl)

Annotated Interactions

No annotated interactions

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