While technically not a nuclear receptor, the AhR is mechanistically and functionally similar to members of that super-family, being both a receptor and a ligand-activated transcription factor. More formally, the AhR is a member of the basic helix-loop-helix, Per-Arnt-Sim family of transcription factors. AhR is a xenobiotic-sensing receptor responsible for the adverse toxicologic effects elicited by various polycyclic aromatic hydrocarbon environmental and industrial pollutants, perhaps the most infamous being
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The basic mechanism of action of dioxin and related compounds has been extensively studied, in particular as it relates to regulation of cytochrome P450 1A1 (CYP1A1).
The AhR is present in the cytosol of most cell types where, in the non-active state, it is in a complex with chaperone proteins such as Hsp90. Binding of a polycyclic aromatic hydrocarbon to AhR leads to nuclear translocation and hetero-dimerization with its partner protein ARNT. The AhR-ARNT hetero-dimer binds to specific cognate DNA sequence elements known as dioxin/xenobiotic response elements (DRE/XRE) present in the regulatory region of a variety of target genes. Binding of AhR:ARNT to these elements, and subsequent recruitment of transcription co-activator complexes, induces the transcription of a battery of target genes, including enobiotic-metabolizing enzymes such as CYP1A1, CYP1A2, CYP2B1 and UGT1A6. In addition, genes affected directly and indirectly by the TCDD/AhR-complex code for both inhibitory and stimulatory growth factors and their gene products affect cellular growth and differentiation leading to tumor promotion and carcinogenicity in addition to induced toxic responses. [INDIGO Catalog No. R06001]WARNING This product is not for human or veterinary use.