Aryl hydrocarbon receptor pathway (Homo sapiens)

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3011, 3234437, 16, 37161341, 4550144913STAT121CyNuHSP9044ActivationTCDD32CyNuNEDD8SUMO7CyNuCyNuNucleusDRE regionCYP1A1p300EBNA-3TCDDCalcium ChannelHsp90pRbARNTRETNrf2EREGFRproliferation and tumorigenesis Nqo1VEGFKLF6CCL1AIPp27Kip1ZAC1PAHXREAIPP631228, 363, 30, 4226, 29L12, 51471424502720, 25, 371811, 32, 39AHRP23AHR19, 44AHR32HSP90HSP9038, 462C-myc33TATAEGFR PathwayTNF-α7CDC37c-src41PRAF1MAP2K1ERK1/2COX-2SRC-143Rel Ap50Rel Ap50p300SRC-110AngiogenesisERAP140RIP140CYP1A1CD36LplNrf2Fgf21GstsGclcOxidative StressRIP140NF-1NCOA7SMRTCYP1A2535CYP1B19, 40Estrogen 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 interactionAcetylationDephosphorylationLEGENDPhosphorylationProteinDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageProteinMoleculep21cip14, 23CDK2RbE2F1Cell cycle inhibitionDetoxification of Xenobiotics and metabolism of xenobioticsCell SurvivalAHRRp300FAS/ FAS-L (Apoptosis)15NRASHRASKRASTCDDPAH3, 30, 4212, 51


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Bibliography

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  1. Kashuba E, Kashuba V, Pokrovskaja K, Klein G, Szekely L; ''Epstein-Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen.''; Oncogene, 2000 PubMed Europe PMC Scholia
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  3. 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
  4. Lu H, Cui W, Klaassen CD; ''Nrf2 protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative injury and steatohepatitis.''; Toxicol Appl Pharmacol, 2011 PubMed Europe PMC Scholia
  5. 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
  6. Coats S, Whyte P, Fero ML, Lacy S, Chung G, Randel E, Firpo E, Roberts JM; ''A new pathway for mitogen-dependent cdk2 regulation uncovered in p27(Kip1)-deficient cells.''; Curr Biol, 1999 PubMed Europe PMC Scholia
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  11. Kimura A, Naka T, Nohara K, Fujii-Kuriyama Y, Kishimoto T; ''Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells.''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC Scholia
  12. 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
  13. Vargiolu M, Fusco D, Kurelac I, Dirnberger D, Baumeister R, Morra I, Melcarne A, Rimondini R, Romeo G, Bonora E; ''The tyrosine kinase receptor RET interacts in vivo with aryl hydrocarbon receptor-interacting protein to alter survivin availability.''; J Clin Endocrinol Metab, 2009 PubMed Europe PMC Scholia
  14. 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
  15. Umannovأ، L, Machala M, Topinka J, Novأ،kovأ، Z, Milcovأ، A, Kozubأ­k A, Vondrأ،cek J; ''Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in rat liver epithelial cells through upregulation of cytochrome P450 1B1 expression.''; Mutat Res, 2008 PubMed Europe PMC Scholia
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  19. Perdew GH; ''Association of the Ah receptor with the 90-kDa heat shock protein.''; J Biol Chem, 1988 PubMed Europe PMC Scholia
  20. Shin S, Wakabayashi N, Misra V, Biswal S, Lee GH, Agoston ES, Yamamoto M, Kensler TW; ''NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis.''; Mol Cell Biol, 2007 PubMed Europe PMC Scholia
  21. Billiard SM, Hahn ME, Franks DG, Peterson RE, Bols NC, Hodson PV; ''Binding of polycyclic aromatic hydrocarbons (PAHs) to teleost aryl hydrocarbon receptors (AHRs).''; Comp Biochem Physiol B Biochem Mol Biol, 2002 PubMed Europe PMC Scholia
  22. 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
  23. 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
  24. Shimada T, Oda Y, Gillam EM, Guengerich FP, Inoue K; ''Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009.''; Drug Metab Dispos, 2001 PubMed Europe PMC Scholia
  25. Park S, Dong B, Matsumura F; ''Rapid activation of c-Src kinase by dioxin is mediated by the Cdc37-HSP90 complex as part of Ah receptor signaling in MCF10A cells.''; Biochemistry, 2007 PubMed Europe PMC Scholia
  26. 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
  27. Nguyen TA, Hoivik D, Lee JE, Safe S; ''Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex.''; Arch Biochem Biophys, 1999 PubMed Europe PMC Scholia
  28. Riese DJ 2nd, Stern DF; ''Specificity within the EGF family/ErbB receptor family signaling network.''; Bioessays, 1998 PubMed Europe PMC Scholia
  29. Tang YM, Wo YY, Stewart J, Hawkins AL, Griffin CA, Sutter TR, Greenlee WF; ''Isolation and characterization of the human cytochrome P450 CYP1B1 gene.''; J Biol Chem, 1996 PubMed Europe PMC Scholia
  30. Lo R, Matthews J; ''High-resolution genome-wide mapping of AHR and ARNT binding sites by ChIP-Seq.''; Toxicol Sci, 2012 PubMed Europe PMC Scholia
  31. Xu S, Weerachayaphorn J, Cai SY, Soroka CJ, Boyer JL; ''Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression.''; Am J Physiol Gastrointest Liver Physiol, 2010 PubMed Europe PMC Scholia
  32. Gottifredi V, McKinney K, Poyurovsky MV, Prives C; ''Decreased p21 levels are required for efficient restart of DNA synthesis after S phase block.''; J Biol Chem, 2004 PubMed Europe PMC Scholia
  33. 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
  34. Kwon TK, Nordin AA; ''Identification of cdk2 binding sites on the p27Kip1 cyclin-dependent kinase inhibitor.''; Oncogene, 1998 PubMed Europe PMC Scholia
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  36. 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
  37. 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
  38. Beischlag TV, Perdew GH; ''ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription.''; J Biol Chem, 2005 PubMed Europe PMC Scholia
  39. Kolluri SK, Weiss C, Koff A, Gأ¶ttlicher M; ''p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells.''; Genes Dev, 1999 PubMed Europe PMC Scholia
  40. Nebert DW, Petersen DD, Puga A; ''Human AH locus polymorphism and cancer: inducibility of CYP1A1 and other genes by combustion products and dioxin.''; Pharmacogenetics, 1991 PubMed Europe PMC Scholia
  41. Ke S, Rabson AB, Germino JF, Gallo MA, Tian Y; ''Mechanism of suppression of cytochrome P-450 1A1 expression by tumor necrosis factor-alpha and lipopolysaccharide.''; J Biol Chem, 2001 PubMed Europe PMC Scholia
  42. Muntanأ©-Relat J, Ourlin JC, Domergue J, Maurel P; ''Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture.''; Hepatology, 1995 PubMed Europe PMC Scholia
  43. 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
  44. Trombino AF, Near RI, Matulka RA, Yang S, Hafer LJ, Toselli PA, Kim DW, Rogers AE, Sonenshein GE, Sherr DH; ''Expression of the aryl hydrocarbon receptor/transcription factor (AhR) and AhR-regulated CYP1 gene transcripts in a rat model of mammary tumorigenesis.''; Breast Cancer Res Treat, 2000 PubMed Europe PMC Scholia
  45. Probst MR, Reisz-Porszasz S, Agbunag RV, Ong MS, Hankinson O; ''Role of the aryl hydrocarbon receptor nuclear translocator protein in aryl hydrocarbon (dioxin) receptor action.''; Mol Pharmacol, 1993 PubMed Europe PMC Scholia
  46. 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
  47. Minami K, Nakajima M, Fujiki Y, Katoh M, Gonzalez FJ, Yokoi T; ''Regulation of insulin-like growth factor binding protein-1 and lipoprotein lipase by the aryl hydrocarbon receptor.''; J Toxicol Sci, 2008 PubMed Europe PMC Scholia
  48. Bell DR, Poland A; ''Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role of hsp90.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  49. Quattrochi LC, Vu T, Tukey RH; ''The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction.''; J Biol Chem, 1994 PubMed Europe PMC Scholia
  50. Madhukar BV, Brewster DW, Matsumura F; ''Effects of in vivo-administered 2,3,7,8-tetrachlorodibenzo-p-dioxin on receptor binding of epidermal growth factor in the hepatic plasma membrane of rat, guinea pig, mouse, and hamster.''; Proc Natl Acad Sci U S A, 1984 PubMed Europe PMC Scholia
  51. 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
  52. Singh NP, Nagarkatti M, Nagarkatti PS; ''Role of dioxin response element and nuclear factor-kappaB motifs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated regulation of Fas and Fas ligand expression.''; Mol Pharmacol, 2007 PubMed Europe PMC Scholia
  53. 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
  54. Hollingshead BD, Petrulis JR, Perdew GH; ''The aryl hydrocarbon (Ah) receptor transcriptional regulator hepatitis B virus X-associated protein 2 antagonizes p23 binding to Ah receptor-Hsp90 complexes and is dispensable for receptor function.''; J Biol Chem, 2004 PubMed Europe PMC Scholia
  55. 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
  56. Landi MT, Bertazzi PA, Baccarelli A, Consonni D, Masten S, Lucier G, Mocarelli P, Needham L, Caporaso N, Grassman J; ''TCDD-mediated alterations in the AhR-dependent pathway in Seveso, Italy, 20 years after the accident.''; Carcinogenesis, 2003 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

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CompareRevisionActionTimeUserComment
126477view20:59, 5 May 2023EgonwAdded an identifier for the calcium channel
121728view01:30, 27 February 2022EweitzUse gene symbols
121727view20:09, 26 February 2022EweitzReplace text node with gene node in complex, and replace its references
121726view19:56, 26 February 2022EweitzCopy BiopaxRef to new node
121725view19:52, 26 February 2022EweitzDraft change
121724view19:35, 26 February 2022EweitzRefine case and copyediting
120796view20:59, 8 January 2022AlexanderPicoReverted to version '04:12, 17 December 2021' by AlexanderPico
120574view11:14, 17 December 2021EweitzModified description
120573view11:12, 17 December 2021EweitzModified title
117654view11:46, 22 May 2021EweitzModified title
115347view10:30, 15 February 2021EgonwMade six more pathways clickable
107439view07:01, 8 October 2019DeSlModified title
107135view14:21, 17 September 2019MaintBotChEBI identifier normalization
106305view17:45, 20 August 2019KhanspersModified description
105536view06:04, 9 August 2019KhanspersModified description
91687view13:42, 29 March 2017DeSlAnnotation update for several datanodes
91671view13:20, 29 March 2017DeSlAnnotation update for angiogenesis
89793view10:53, 6 October 2016Mkutmonfixed special character in datanode label
88982view09:41, 18 August 2016MirellaKalafatiOntology Term : 'regulatory pathway' added !
88981view09:40, 18 August 2016MirellaKalafatiReverted to version '08:09, 17 August 2016' by MirellaKalafati
88901view08:13, 17 August 2016MirellaKalafatiOntology Term : 'cancer pathway' added !
88900view08:09, 17 August 2016MirellaKalafatiOntology Term : 'signaling pathway' added !
88899view08:09, 17 August 2016MirellaKalafatiOntology Term : 'DOID:5395' removed !
85335view16:12, 7 May 2016EgonwReplaced a mim-conversion with Arrow.
79995view21:04, 29 April 2015ZariAnnotated EBNA-3,COX-2,ERK1/2 , CYP1A1 and Gsts
78547view10:30, 7 January 2015MaintBotadded missing graphIds
76318view06:58, 2 July 2014Mkutmonfixed datasource for pRb datanode
73592view16:10, 3 February 2014Prakamya1986Modified description
73591view16:06, 3 February 2014Prakamya1986Modified description
73590view15:53, 3 February 2014Prakamya1986Specify description
73436view16:30, 28 January 2014Prakamya1986Specify description
73435view16:20, 28 January 2014Prakamya1986Specify description
73434view16:16, 28 January 2014Prakamya1986Periodical save, work in progress
73433view16:09, 28 January 2014Prakamya1986Specify description
73432view16:05, 28 January 2014Prakamya1986Periodical save, work in progress
73431view15:54, 28 January 2014Prakamya1986Specify description
73430view15:52, 28 January 2014Prakamya1986Specify description
73429view14:44, 28 January 2014Prakamya1986Specify description
73385view12:14, 25 January 2014Prakamya1986Specify description
73384view12:13, 25 January 2014Prakamya1986Specify description
73383view12:12, 25 January 2014Prakamya1986Specify description
73340view17:01, 21 January 2014Prakamya1986Specify description
73339view16:54, 21 January 2014Prakamya1986Specify description
73338view16:50, 21 January 2014Prakamya1986Specify description
73337view16:39, 21 January 2014Prakamya1986Specify description
73336view16:27, 21 January 2014Prakamya1986Specify description
73335view16:18, 21 January 2014Prakamya1986Specify description
73334view16:03, 21 January 2014Prakamya1986Specify description
73333view15:59, 21 January 2014Prakamya1986Periodical save, work in progress
73332view15:31, 21 January 2014Prakamya1986Specify description

External references

DataNodes

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NameTypeDatabase referenceComment
AHRGeneProduct196 (Entrez Gene)
AHRRGeneProduct57491 (Entrez Gene)
AIPGeneProductENSG00000110711 (Ensembl)
ARNTGeneProduct405 (Entrez Gene)
AngiogenesisPathway
C-mycProtein4609 (Entrez Gene)
CCL1GeneProduct6346 (Entrez Gene) PMID: 16679317 PAHs induce expression of the chemokine CCL1 in an AhR- and calcium-dependent manner.
CD36GeneProduct948 (Entrez Gene)
CDC37GeneProduct11140 (Entrez Gene)
CDK2GeneProduct1017 (Entrez Gene)
COX-2GeneProduct5743 (Entrez Gene)
CYP1A1Protein
CYP1A1GeneProduct1543 (Entrez Gene)
CYP1A2GeneProduct1544 (Entrez Gene)
CYP1B1GeneProduct1545 (Entrez Gene)
Calcium Channel
Cell SurvivalPathway
Cell cycle inhibitionPathway
DRE regionComplex
Detoxification of Xenobiotics and metabolism of xenobiotics Pathway
E2F1GeneProduct1869 (Entrez Gene)
EBNA-3Protein17494212 (Entrez Gene)
EGFR Pathway
EGFRGeneProduct1956 (Entrez Gene)
ERProtein2099 (Entrez Gene) Estrogen Receptor
ERAP140Protein
ERK1/2 Protein
Estrogen Metabolism and modulation of Estrogen receptor signallingPathway
FAS/ FAS-L (Apoptosis)Pathway
Fgf21Protein26291 (Entrez Gene)
GclcProtein2729 (Entrez Gene)
GstsProtein
HRASGeneProductENSG00000174775 (Ensembl)
HSP90GeneProduct3320 (Entrez Gene)
Hsp90Protein3320 (Entrez Gene)
KLF6GeneProduct1316 (Entrez Gene)
KRASGeneProductENSG00000133703 (Ensembl)
LplProtein
MAP2K1GeneProductENSG00000169032 (Ensembl)
NCOA7Protein135112 (Entrez Gene)
NF-1Protein4763 (Entrez Gene)
NRASGeneProductENSG00000213281 (Ensembl)
Nqo1Protein1728 (Entrez Gene)
Nrf2GeneProduct4780 (Entrez Gene)
Oxidative Stress Pathway
P23GeneProductENSG00000110711 (Ensembl)
PAHMetabolite33848 (ChEBI)
ProteinGeneProduct
ProteinProtein5894 (Entrez Gene)
RAF1GeneProductENSG00000132155 (Ensembl)
RETProtein5979 (Entrez Gene)
RIP140Protein8204 (Entrez Gene)
RbGeneProduct5925 (Entrez Gene)
Rel AGeneProduct5970 (Entrez Gene)
SMRTProtein9612 (Entrez Gene)
SRC-1GeneProduct84722 (Entrez Gene)
TATAComplex
TCDDMetabolite28119 (ChEBI)
TNF-αGeneProduct7124 (Entrez Gene)
VEGFGeneProduct7422 (Entrez Gene)
XRExenobiotic- responsive element
ZAC1Protein5325 (Entrez Gene)
c-srcProtein6714 (Entrez Gene)
p21cip1GeneProduct1026 (Entrez Gene)
p27Kip1GeneProduct1027 (Entrez Gene)
p300Protein2033 (Entrez Gene)
p50GeneProduct4790 (Entrez Gene)
pRbProteinP06400.2 (Uniprot-SwissProt)
proliferation and tumorigenesis Pathway

Annotated Interactions

No annotated interactions

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