The aryl hydrocarbon receptor, highly expressed in the liver and barrier organs, is resident in the cytoplasm bound to the chaperone heat shock protein hsp90. Upon agonist activation, the ligand:aryl hydrocarbon receptor complex migrates to the nucleus and binds the aryl hydrocarbon receptor nuclear translocator (ARNT, P27540, also known as HIF1β). The complex regulates transcription of selected genes through interaction with xenobiotic response elements (XRE). Among the genes regulated by the AHR/ARNT complex are cytochrome P450s, particularly CYP1A1, and the period circadian protein homolog 1 (PER1, O15534). The aryl hydrocarbon receptor is also capable of non-genomic signalling.

* Key recommended reading is highlighted with an asterisk

* Bock KW. (2019) Aryl hydrocarbon receptor (AHR): From selected human target genes and crosstalk with transcription factors to multiple AHR functions. Biochem Pharmacol, 168: 65-70. [PMID:31228464]

* Bock KW. (2020) Aryl hydrocarbon receptor (AHR) functions: Balancing opposing processes including inflammatory reactions. Biochem Pharmacol, 178: 114093. [PMID:32535108]

Esser C, Rannug A. (2015) The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol Rev, 67 (2): 259-79. [PMID:25657351]

* Roman ÁC, Carvajal-Gonzalez JM, Merino JM, Mulero-Navarro S, Fernández-Salguero PM. (2018) The aryl hydrocarbon receptor in the crossroad of signalling networks with therapeutic value. Pharmacol Ther, 185: 50-63. [PMID:29258844]

* Rothhammer V, Quintana FJ. (2019) The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat Rev Immunol, 19 (3): 184-197. [PMID:30718831]

* Shi Y, Zeng Z, Yu J, Tang B, Tang R, Xiao R. (2020) The aryl hydrocarbon receptor: An environmental effector in the pathogenesis of fibrosis. Pharmacol Res, 160: 105180. [PMID:32877693]

* Sládeková L, Mani S, Dvořák Z. (2023) Ligands and agonists of the aryl hydrocarbon receptor AhR: Facts and myths. Biochem Pharmacol, 213: 115626. [PMID:37247746]

1. Bjeldanes LF, Kim JY, Grose KR, Bartholomew JC, Bradfield CA. (1991) Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci USA, 88 (21): 9543-7. [PMID:1658785]

2. Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, Coquery CM, Neil J, Pryor WM, Mayhew D et al.. (2017) Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans. J Invest Dermatol, 137 (10): 2110-2119. [PMID:28595996]

3. Wilkinson IVL, Perkins KJ, Dugdale H, Moir L, Vuorinen A, Chatzopoulou M, Squire SE, Monecke S, Lomow A, Geese M et al.. (2020) Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid. Angew Chem Int Ed Engl, 59 (6): 2420-2428. [PMID:31755636]