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Two major types of environmental compounds can activate AHR signaling: halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAH) such as benzo(a)pyrene. Unliganded AHR forms a complex in the cytosol with two copies of 90kD heat shock protein (HSP90AB1), one X-associated protein (AIP), and one p23 molecular chaperone protein (PTGES3). After ligand binding and activation, the AHR complex translocates to the nucleus, disassociates from the chaperone subunits, dimerises with the aryl hydrocarbon receptor nuclear translocator (ARNT) and transactivates target genes via binding to xenobiotic response elements (XREs) in their promoter regions. AHR targets genes of Phase I and Phase II metabolism, such as cytochrome P450 1A1 (CYP1A1), cytochorme P450 1B1 (CYP1B1), NAD(P)H:quinone oxidoreductase I (NQO1) and aldehyde dehydrogenase 3 (ALHD3A1). This is thought to be an organism\u0027s response to foreign chemical exposure and normally, foreign chemicals are made less reactive by the induction and therefore increased activity of these enzymes (Beischlag et al. 2008).\u003cbr\u003e\u003cbr\u003eAHR itself is regulated by the aryl hydrocarbon receptor repressor (AHRR, aka BHLHE77, KIAA1234), an evolutionarily conserved bHLH-PAS protein that inhibits both xenobiotic-induced and constitutively active AHR transcriptional activity in many species. AHRR resides predominantly in the nuclear compartment where it competes with AHR for binding to ARNT. As a result, there is competition between AHR:ARNT and AHRR:ARNT complexes for binding to XREs in target genes and AHRR can repress the transcription activity of AHR (Hahn et al. 2009, Haarmann-Stemmann \u0026 Abel 2006)."},{"key":"rdfs:label","value":"Aryl hydrocarbon receptor signalling"},{"key":"date","value":"2026-07-02"},{"key":"providedBy","value":"https://reactome.org"},{"key":"contributor","value":"GOC:reactome_curators"},{"key":"contributor","value":"Reviewed: D\u0027Eustachio, Peter, 2016-10-11"}]},{"id":"gomodel:ev_w_id_R-HSA-8936849_BFO_0000050_R-HSA-8937144/R-HSA-8937144_Reactome_R-HSA-8937144","type":[{"type":"class","id":"ECO:0000313","label":"imported information used in automatic 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