Aryl Hydrocarbon Receptor

Aryl Hydrocarbon Receptor (AhR or AHR) is a cytoplasmic receptor and transcription factor that belongs to the family of basic helix-loop-helix transcription factors. The AhR is activated or inhibited by various types of exogenous and endogenous ligands. AhR is an important factor in immunity and tissue homeostasis, and structurally diverse compounds from the environment, diet, microbiome, and host metabolism can induce AhR activity, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Endogenous ligands include indigoids, heme metabolites, eicosanoids, tryptophan derivatives, and equilenin. Exogenous ligands include polycyclic aromatic hydrocarbons, polychlorinated biphenyls, natural compounds, and small molecule compounds. The different structures and properties of AhR ligands mean that when they combine with AhR they have distinct biological effects.

Unliganded AHR is sequestered in the cytoplasm by chaperone proteins including Hsp90, AHR-interacting protein (AIP), and p23. Upon ligand binding, AHR translocates to the nucleus and heterodimerizes with ARNT. The AHR-ARNT complex regulates transcription by binding with high affinity to specific DNA sequences termed aryl hydrocarbon response elements located in the regulatory regions of target genes including CYP1A1, CYP1B1, and TIPARP.

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