Constitutive androstane receptor pathway (WP2875)

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 [https://assays.cancer.gov/available_assays?wp_id=WP2875 CPTAC Assay Portal]
last edited

Authors

Riannefijten, Egonw, MaintBot, Khanspers, Fehrhart, Mkutmon, Ariutta, AlexanderPico, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: signaling pathway

Participants

Label Type Compact Identifier
Ligand Metabolite chebi:77326
NR1I3 GeneProduct ncbigene:9970
RXRA GeneProduct ncbigene:6256
PPP2R4 GeneProduct ensembl:ENSG00000119383
HSP90AA1 GeneProduct ncbigene:3320
NR1I3 GeneProduct ncbigene:9970
Ligand Metabolite chebi:77326
HSP90AA1 GeneProduct ncbigene:3320
RXRA GeneProduct ncbigene:6256
NR1I3 GeneProduct ncbigene:9970
Ligand Metabolite chebi:77326
DNAJC7 GeneProduct ncbigene:7266
DNAJC7 GeneProduct ncbigene:7266
NCOA6 GeneProduct ncbigene:23054
SP1 GeneProduct ncbigene:6667
NCOA1 GeneProduct ncbigene:8648
PPARGC1A GeneProduct ncbigene:10891
NCOA2 GeneProduct ncbigene:10499
SMC1A GeneProduct ncbigene:8243
CYP2C9 GeneProduct ncbigene:1559
ABCB1 GeneProduct ncbigene:5243
UGT1A1 GeneProduct ensembl:ENSG00000241635
ABCC2 GeneProduct ncbigene:1244
CYP2A6 GeneProduct ncbigene:1548
CYP4A11 GeneProduct ensembl:ENSG00000187048
CYP2C19 GeneProduct ncbigene:1557
SULT1A1 GeneProduct ensembl:ENSG00000196502
GSTA2 GeneProduct ncbigene:2939
CYP3A5 GeneProduct ncbigene:1577
SULT2A1 GeneProduct ensembl:ENSG00000105398
CYP3A4 GeneProduct ncbigene:1576
ALAS1 GeneProduct ensembl:ENSG00000023330
EHHADH GeneProduct ensembl:ENSG00000113790
CYP2B6 GeneProduct ncbigene:1555
ABCC3 GeneProduct ncbigene:8714
UGT1A4 GeneProduct ensembl:ENSG00000244474
UGT1A6 GeneProduct ensembl:ENSG00000167165
UGT1A9 GeneProduct ensembl:ENSG00000241119
UGT1A3 GeneProduct ensembl:ENSG00000243135
FOXO1 GeneProduct ensembl:ENSG00000150907

References

  1. Sugatani J, Kojima H, Ueda A, Kakizaki S, Yoshinari K, Gong QH, et al. The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology. 2001 May;33(5):1232–8. PubMed Europe PMC Scholia
  2. Cai Y, Konishi T, Han G, Campwala KH, French SW, Wan Y-JY. The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways. Eur J Pharm Sci. 2002 Feb;15(1):89–96. PubMed Europe PMC Scholia
  3. Willson TM, Kliewer SA. PXR, CAR and drug metabolism. Nat Rev Drug Discov. 2002 Apr;1(4):259–66. PubMed Europe PMC Scholia
  4. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, et al. Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem. 2003 May 9;278(19):17277–83. PubMed Europe PMC Scholia
  5. 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 May 7;279(19):19832–8. PubMed Europe PMC Scholia
  6. 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 Sep;24(18):7931–40. PubMed Europe PMC Scholia
  7. Handschin C, Meyer UA. Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys. 2005 Jan 15;433(2):387–96. PubMed Europe PMC Scholia
  8. Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, et al. A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer. Mol Cell. 2004 Dec 22;16(6):919–28. PubMed Europe PMC Scholia
  9. Timsit YE, Negishi M. CAR and PXR: the xenobiotic-sensing receptors. Steroids. 2007 Mar;72(3):231–46. PubMed Europe PMC Scholia
  10. 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 Sep;21(9):2099–111. PubMed Europe PMC Scholia
  11. 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 Feb;9(2):129–43. PubMed Europe PMC Scholia
  12. 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 Jul 1;82(1):9–16. PubMed Europe PMC Scholia
  13. Fijten RRR, Jennen DGJ, van Delft JHM. Pathways for ligand activated nuclear receptors to unravel the genomic responses induced by hepatotoxicants. Curr Drug Metab. 2013 Dec;14(10):1022–8. PubMed Europe PMC Scholia