FIG. 1.
The classical mechanism of AhR-dependent gene activation. Ligand diffuses into the cell and binds to the cytosolic AhR complex resulting in the exposure of its nuclear localization sequence (NLS), likely dissociation of XAP2 from the complex and nuclear translocation of the activated AhR complex. Once in the nucleus, chaperone proteins (hsp90 and p23) are displaced from the AhR by ARNT, and the resulting AhR:ARNT dimers bind to and activate transcription from the DRE-containing promoters such as those for various CYPs, SOS1, AhRR, and TriPARP affecting indicated cellular pathways. The AhRR lacks a transactivation domain and exerts negative feedback regulation on the AhR pathway through its competition for ARNT and formation of inactive AhRR:ARNT transcriptional complexes on DREs. Following transcription, AhR is exported and degraded by the proteosome in the cytoplasm. Activation of CYPs can result in metabolism of exogenous and endogenous AhR ligands.