Constitutive androstane receptor pathway (WP2875)

Homo sapiens

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]

Authors

Rianne Fijten , Egon Willighagen , Kristina Hanspers , Friederike Ehrhart , Martina Summer-Kutmon , Anders Riutta , Alex Pico , and Eric Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

signaling pathway

Participants

Label Type Compact URI Comment
Ligand Metabolite chebi:77326
NR1I3 GeneProduct ncbigene:9970 nuclear receptor subfamily 1, group I, member 3
RXRA GeneProduct ncbigene:6256 retinoid X receptor, alpha
PPP2R4 GeneProduct ensembl:ENSG00000119383 plays a role in translocation of CAR
HSP90AA1 GeneProduct ncbigene:3320 heat shock protein 90kDa alpha (cytosolic), class A member 1
DNAJC7 GeneProduct ncbigene:7266 DnaJ (Hsp40) homolog, subfamily C, member 7
NCOA6 GeneProduct ncbigene:23054 nuclear receptor coactivator 6
SP1 GeneProduct ncbigene:6667 Sp1 transcription factor
NCOA1 GeneProduct ncbigene:8648 nuclear receptor coactivator 1
PPARGC1A GeneProduct ncbigene:10891 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha
NCOA2 GeneProduct ncbigene:10499 nuclear receptor coactivator 2
SMC1A GeneProduct ncbigene:8243 structural maintenance of chromosomes 1A
CYP2C9 GeneProduct ncbigene:1559 cytochrome P450, family 2, subfamily C, polypeptide 9
ABCB1 GeneProduct ncbigene:5243 ATP-binding cassette, sub-family B (MDR/TAP), member 1
UGT1A1 GeneProduct ensembl:ENSG00000241635
ABCC2 GeneProduct ncbigene:1244 ATP-binding cassette, sub-family C (CFTR/MRP), member 2
CYP2A6 GeneProduct ncbigene:1548 cytochrome P450, family 2, subfamily A, polypeptide 6
CYP4A11 GeneProduct ensembl:ENSG00000187048
CYP2C19 GeneProduct ncbigene:1557 cytochrome P450, family 2, subfamily C, polypeptide 19
SULT1A1 GeneProduct ensembl:ENSG00000196502 during fasting
GSTA2 GeneProduct ncbigene:2939 glutathione S-transferase alpha 2
CYP3A5 GeneProduct ncbigene:1577 cytochrome P450, family 3, subfamily A, polypeptide 5
SULT2A1 GeneProduct ensembl:ENSG00000105398
CYP3A4 GeneProduct ncbigene:1576 cytochrome P450, family 3, subfamily A, polypeptide 4
ALAS1 GeneProduct ensembl:ENSG00000023330
EHHADH GeneProduct ensembl:ENSG00000113790
CYP2B6 GeneProduct ncbigene:1555 cytochrome P450, family 2, subfamily B, polypeptide 6
ABCC3 GeneProduct ncbigene:8714 ATP-binding cassette, sub-family C (CFTR/MRP), member 3
UGT1A4 GeneProduct ensembl:ENSG00000244474
UGT1A6 GeneProduct ensembl:ENSG00000167165
UGT1A9 GeneProduct ensembl:ENSG00000241119
UGT1A3 GeneProduct ensembl:ENSG00000243135
FOXO1 GeneProduct ensembl:ENSG00000150907

References

  1. The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Sugatani J, Kojima H, Ueda A, Kakizaki S, Yoshinari K, Gong QH, et al. Hepatology. 2001 May;33(5):1232–8. PubMed Europe PMC Scholia
  2. The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways. Cai Y, Konishi T, Han G, Campwala KH, French SW, Wan YJY. Eur J Pharm Sci. 2002 Feb;15(1):89–96. PubMed Europe PMC Scholia
  3. PXR, CAR and drug metabolism. Willson TM, Kliewer SA. Nat Rev Drug Discov. 2002 Apr;1(4):259–66. PubMed Europe PMC Scholia
  4. Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, et al. J Biol Chem. 2003 May 9;278(19):17277–83. PubMed Europe PMC Scholia
  5. The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. Maglich JM, Watson J, McMillen PJ, Goodwin B, Willson TM, Moore JT. J Biol Chem. 2004 May 7;279(19):19832–8. PubMed Europe PMC Scholia
  6. Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Kodama S, Koike C, Negishi M, Yamamoto Y. Mol Cell Biol. 2004 Sep;24(18):7931–40. PubMed Europe PMC Scholia
  7. Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Handschin C, Meyer UA. Arch Biochem Biophys. 2005 Jan 15;433(2):387–96. PubMed Europe PMC Scholia
  8. A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer. Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, et al. Mol Cell. 2004 Dec 22;16(6):919–28. PubMed Europe PMC Scholia
  9. CAR and PXR: the xenobiotic-sensing receptors. Timsit YE, Negishi M. Steroids. 2007 Mar;72(3):231–46. PubMed Europe PMC Scholia
  10. 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. Echchgadda I, Song CS, Oh T, Ahmed M, De La Cruz IJ, Chatterjee B. Mol Endocrinol. 2007 Sep;21(9):2099–111. PubMed Europe PMC Scholia
  11. Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Pavek P, Dvorak Z. Curr Drug Metab. 2008 Feb;9(2):129–43. PubMed Europe PMC Scholia
  12. From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Bock KW. Biochem Pharmacol. 2011 Jul 1;82(1):9–16. PubMed Europe PMC Scholia
  13. Pathways for ligand activated nuclear receptors to unravel the genomic responses induced by hepatotoxicants. Fijten RRR, Jennen DGJ, van Delft JHM. Curr Drug Metab. 2013 Dec;14(10):1022–8. PubMed Europe PMC Scholia