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. 2023 Aug 31;24(17):13537. doi: 10.3390/ijms241713537

Figure 1.

Figure 1

Schematic representation of the canonical and non-canonical signalling pathways of AhR. AhR is found in the cytosol in its latent form associated with a protein complex (HSP90: heat shock protein, XAP2: hepatitis B virus X-associated protein, SRC: Proto-Oncogene tyrosine-protein kinase s-Src and p23). After activation by ligands, it translocates to the nucleus and forms a heterodimer with AhR nuclear translocator (ARNT-), which acts as a transcriptional factor, increasing gene expression contained in the Xenobiotic response element (XRE). This is the canonical pathway and affects the expression of genes such as CYP1A1, CYP1B1, CYP1A2, AhR repressor (AhRR), or indoleamine 2,3-dioxygenase (IDO1). By non-canonical pathway, AhR binds other proteins such as pRB, NF-κB, c-Maf, or KLF6 and increases the expression of genes contained in the Non-consensus Xenobiotic response element (NC-XRE). Moreover, when AhR is activated by ligands, the release of c-Src (SRC) can activate epidermal growth factor receptor (EGFR) signalling. Finally, AhR is degraded by proteasome in the cytosol, which is one of the possible degradation pathways. Image created using BioRender.