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. Author manuscript; available in PMC: 2020 Apr 24.
Published in final edited form as: Trends Immunol. 2018 Nov 5;39(12):1005–1020. doi: 10.1016/j.it.2018.10.010

Figure 1: The AhR transcriptional circuit in mammalian cells.

Figure 1:

The inactive form of the aryl hydrocarbon receptor (AhR) is present in the cytosol as a complex with the chaperone proteins HSP90, P23, and AIP. Multiple AhR ligands from the gut microbiome, host metabolism, diet, and environment induce a conformational change in AhR exposing the nuclear localization signal initiating nuclear shuttling. Recently an additional mechanism was shown to activate AhR via DNA exposed on apoptotic cells or apoptotic microparticles dependent on Toll-Like Receptor 9 (TLR9) [4]. Once in the nucleus, AhR forms a dimer with the AhR nuclear translocator (ARNT) binding to the XRE/DRE sequence motif 5’-GCGTG-3’. This induces expression of genes involved in AhR ligand metabolism and immune regulation. Furthermore, AhR drives expression of AhR repressor (AHRR) disrupting the AhR/ARNT heterodimer and suppressing its transcriptional activity. In addition, AhR functions as a CUL4B-based E3 ubiquitin ligase complex driving selective protein degradation. Regulation of AhR pathway is controlled through nuclear export and subsequent degradation of AhR via the ubiquitin-proteasome pathway.