Ahr Signal Pathway

AHR (Aryl Hydrocarbon Receptor), a member of the bHLH (basic Helix–Loop–Helix)/PAS (Per-ARNT-Sim) transcription factor family, exists in a dormant state in cytoplasma in association with a complex of HSP90 (Heat Shock Protein-90), XAP2 (X-Associated Protein 2). Upon ligand binding, AHR is activated through conformational change that exposes NLS (Nuclear Localization Signal) and translocates to the nucleus. It forms a heterodimer with ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator). The heterodimer binds to the XRE (Xenobiotic Responsive Element) and alters expression of several genes in the metabolism of xenobiotic that are controlled by XRE enhancers. These genes include CYP1A1, CYP1B1, NAD(P)h-Quinone Oxidoreductase.

Ligands for AHR are diverse, including dietary compounds, flavonoids, natural products and pharmaceuticals. AHR is also known as Dioxin receptor, which binds to PAH (Polycyclic Aromatic Hydrocarbons), Dioxins (e.g. 2,3,7,8-tetracholoridibenzo-p-dioxin) and Polychorinated Biphenyls.

AHR interacts with various cellular signaling proteins to impact transcription regulation. It also interact with other signal transduction pathways such as those mediated by ESR and other hormone receptors, Hypoxia, NF-kB and Rb protein.