Aryl hydrocarbon receptor (Bos taurus)

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359, 282734233111, 25, 4513234026, 36745224, 3933STAT119CyNuHSP9017ActivationTCDD28CyNuNEDD8SUMO7CyNuCyNuNucleusProteinProteinDRE regionKLF6NQO1proliferation and tumorigenesis EGFRCYP1A1PAHAIPEBNA-3ARNTESR1HSP90AA1RETRB1TCDDEP300Calcium ChannelVEGFAXRECCL1CDKN1BPLAGL1NFE2L26, 154346AIP3747, 563111, 48, 509, 28, 555744, 524947P16, 35, 54L30AHRAIPAHR3, 17AHRHSP90AA128HSP90AA141, 4232MYC53TATAEGFR PathwayTNF25CDC37SRC26PRAF1PMAP2K1MAPK1PPGHS-233PSRC1RELANFKB1RELANFKB1EP300PSRC12AngiogenesisNCOA7NRIP1CYP1A1CD36LPLNFE2L222FGF21HPGDSGCLCOxidative StressNRIP1NF1NCOA75NCOR2CYP1A22021CYP1B118, 29Estrogen Metabolism and modulation of Estrogen receptor signallingEnzyme ComplexProteinReceptorLigandmRNASmall moleculeInduced activationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageMoleculeCDKN1ACDK210, 51RB1E2F1Cell cycle inhibitionDetoxification of Xenobiotics and metabolism of xenobioticsCell SurvivalAHRREP30012FAS/ FAS-L (Apoptosis)NRASHRASKRASTCDD16, 35, 54PAH6, 15Cell Survival1


Description

The Aryl Hydrocarbon receptor (AhR) is ligand activated transcription factor that regulates wide spectrum of gene expression. The main mediator of AhR is 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) or polycyclic aromatic hydrocarbons which are widespread environmental pollutant causing a variety of severe health effects, e.g. immunosuppression, carcinogenesis and hepatotoxicity.

AhR is a member of basic helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily of transcription factors. In the absence of ligand, the AhR can be found in the cytosol, bound to a dimer of the heat shock protein of 90 kDa (Hsp90) and the immunophilin-like protein, AIP (also known as XAP2 and ARA9). Upon ligand binding, the AHR translocates to the nucleus and binds with ARNT. The AHR/ARNT heterodimer binds to xenobiotic response elements and regulates a diverse set of genes

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP2586(79995) with a 96.0% conversion rate.

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Ontology Terms

 

Bibliography

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  37. Chahal HS, Trivellin G, Leontiou CA, Alband N, Fowkes RC, Tahir A, Igreja SC, Chapple JP, Jordan S, Lupp A, Schulz S, Ansorge O, Karavitaki N, Carlsen E, Wass JA, Grossman AB, Korbonits M; ''Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway.''; J Clin Endocrinol Metab, 2012 PubMed Europe PMC Scholia
  38. Mayati A, Levoin N, Paris H, N'Diaye M, Courtois A, Uriac P, Lagadic-Gossmann D, Fardel O, Le Ferrec E; ''Induction of intracellular calcium concentration by environmental benzo(a)pyrene involves a خ²2-adrenergic receptor/adenylyl cyclase/Epac-1/inositol 1,4,5-trisphosphate pathway in endothelial cells.''; J Biol Chem, 2012 PubMed Europe PMC Scholia
  39. Miao W, Hu L, Scrivens PJ, Batist G; ''Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: direct cross-talk between phase I and II drug-metabolizing enzymes.''; J Biol Chem, 2005 PubMed Europe PMC Scholia
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  42. Soshilov A, Denison MS; ''Ligand displaces heat shock protein 90 from overlapping binding sites within the aryl hydrocarbon receptor ligand-binding domain.''; J Biol Chem, 2011 PubMed Europe PMC Scholia
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  44. Elferink CJ, Ge NL, Levine A; ''Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein.''; Mol Pharmacol, 2001 PubMed Europe PMC Scholia
  45. Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH, Parsons SJ; ''c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  46. N'Diaye M, Le Ferrec E, Lagadic-Gossmann D, Corre S, Gilot D, Lecureur V, Monteiro P, Rauch C, Galibert MD, Fardel O; ''Aryl hydrocarbon receptor- and calcium-dependent induction of the chemokine CCL1 by the environmental contaminant benzo[a]pyrene.''; J Biol Chem, 2006 PubMed Europe PMC Scholia
  47. 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 PubMed Europe PMC Scholia
  48. Riese DJ 2nd, Stern DF; ''Specificity within the EGF family/ErbB receptor family signaling network.''; Bioessays, 1998 PubMed Europe PMC Scholia
  49. Monteiro P, Gilot D, Le Ferrec E, Rauch C, Lagadic-Gossmann D, Fardel O; ''Dioxin-mediated up-regulation of aryl hydrocarbon receptor target genes is dependent on the calcium/calmodulin/CaMKIalpha pathway.''; Mol Pharmacol, 2008 PubMed Europe PMC Scholia
  50. Madhukar BV, Ebner K, Matsumura F, Bombick DW, Brewster DW, Kawamoto T; ''2,3,7,8-Tetrachlorodibenzo-p-dioxin causes an increase in protein kinases associated with epidermal growth factor receptor in the hepatic plasma membrane.''; J Biochem Toxicol, 1988 PubMed Europe PMC Scholia
  51. Kwon TK, Nordin AA; ''Identification of cdk2 binding sites on the p27Kip1 cyclin-dependent kinase inhibitor.''; Oncogene, 1998 PubMed Europe PMC Scholia
  52. Ge NL, Elferink CJ; ''A direct interaction between the aryl hydrocarbon receptor and retinoblastoma protein. Linking dioxin signaling to the cell cycle.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  53. Kim DW, Gazourian L, Quadri SA, Romieu-Mourez R, Sherr DH, Sonenshein GE; ''The RelA NF-kappaB subunit and the aryl hydrocarbon receptor (AhR) cooperate to transactivate the c-myc promoter in mammary cells.''; Oncogene, 2000 PubMed Europe PMC Scholia
  54. Poland A, Glover E, Kende AS; ''Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase.''; J Biol Chem, 1976 PubMed Europe PMC Scholia
  55. Takahata S, Sogawa K, Kobayashi A, Ema M, Mimura J, Ozaki N, Fujii-Kuriyama Y; ''Transcriptionally active heterodimer formation of an Arnt-like PAS protein, Arnt3, with HIF-1a, HLF, and clock.''; Biochem Biophys Res Commun, 1998 PubMed Europe PMC Scholia
  56. Ahmed S, Valen E, Sandelin A, Matthews J; ''Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters.''; Toxicol Sci, 2009 PubMed Europe PMC Scholia
  57. Roman AC, Carvajal-Gonzalez JM, Rico-Leo EM, Fernandez-Salguero PM; ''Dioxin receptor deficiency impairs angiogenesis by a mechanism involving VEGF-A depletion in the endothelium and transforming growth factor-beta overexpression in the stroma.''; J Biol Chem, 2009 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
117477view10:59, 21 May 2021EweitzModified title
107071view14:15, 17 September 2019MaintBotChEBI identifier normalization
89410view20:18, 10 September 2016AlexanderPicoOntology Term : 'signaling pathway' added !
89133view21:49, 22 August 2016AriuttaOntology Term : 'regulatory pathway' added !
85345view10:13, 9 May 2016EgonwReplaced a mim-conversion with Arrow.
80830view15:27, 30 June 2015MkutmonNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AHRGeneProductENSBTAG00000007746 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:196
AHRRGeneProductENSBTAG00000026527 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57491
AIPGeneProductENSBTAG00000010478 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000110711
ARNTGeneProductENSBTAG00000021037 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:405
AngiogenesisPathway
CCL1GeneProductENSBTAG00000008832 (Ensembl)
  • PMID: 16679317 PAHs induce expression of the chemokine CCL1 in an AhR- and calcium-dependent manner.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6346
CD36GeneProductENSBTAG00000014220 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:948
CDC37GeneProductENSBTAG00000011699 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11140
CDK2GeneProductENSBTAG00000004021 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1017
CDKN1AGeneProductENSBTAG00000008353 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1026
CDKN1BGeneProductENSBTAG00000018254 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1027
CYP1A1ProteinENSBTAG00000001021 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1543
CYP1A2GeneProductENSBTAG00000000085 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1544
CYP1B1GeneProductENSBTAG00000010531 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1545
Calcium Channel
Cell SurvivalPathway
Cell Survival Pathway
Cell cycle inhibitionPathway
DRE regionComplex
Detoxification of Xenobiotics and metabolism of xenobiotics Pathway
E2F1GeneProductENSBTAG00000003971 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1869
EBNA-3Protein
EGFR Pathway
EGFRGeneProductENSBTAG00000011628 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1956
EP300ProteinENSBTAG00000016198 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2033
ESR1ProteinENSBTAG00000007159 (Ensembl)
  • Estrogen Receptor
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2099
Estrogen Metabolism and modulation of Estrogen receptor signallingPathway
FAS/ FAS-L (Apoptosis)Pathway
FGF21ProteinENSBTAG00000011624 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:26291
GCLCProteinENSBTAG00000015571 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2729
HPGDSProteinENSBTAG00000017073 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:27306
HRASGeneProductENSBTAG00000046644 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000174775
HSP90AA1GeneProductENSBTAG00000006270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3320
KLF6GeneProductENSBTAG00000015188 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1316
KRASGeneProduct
LPLProteinENSBTAG00000012855 (Ensembl)
  • lipoprotein lipase
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4023
MAP2K1GeneProductENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000169032
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MYCProteinENSBTAG00000008409 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4609
NCOA7ProteinENSBTAG00000011911 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:135112
NCOR2ProteinENSBTAG00000024603 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9612
NF1ProteinENSBTAG00000011829 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4763
NFE2L2GeneProductENSBTAG00000019255 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4780
NFKB1GeneProductENSBTAG00000020270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
NQO1ProteinENSBTAG00000020632 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1728
NRASGeneProductENSBTAG00000046797 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000213281
NRIP1ProteinENSBTAG00000047293 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8204
Oxidative Stress Pathway
PAHMetaboliteCHEBI:33848 (ChEBI)
PGHS-2GeneProductENSBTAG00000014127 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5743
PLAGL1ProteinENSBTAG00000026523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5325
PSRC1GeneProductENSBTAG00000018806 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:84722
RAF1GeneProductENSBTAG00000045748 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000132155
RB1GeneProductENSBTAG00000006640 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5925
RELAGeneProductENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RETProteinENSBTAG00000000570 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5979
SRCProteinENSBTAG00000008938 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
TATAComplex
TCDDMetaboliteCHEBI:28119 (ChEBI)
TNFGeneProductENSBTAG00000025471 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7124
VEGFAGeneProductENSBTAG00000047561 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7422
XRExenobiotic responsive element
proliferation and tumorigenesis Pathway

Annotated Interactions

No annotated interactions
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP3226"
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