fig4

Figure 4. The aryl hydrocarbon receptor (AHR). The AHR is found in the cytoplasm bound to protein chaperone molecules, including AHR interacting protein, heat shock protein-90, the p53 protein, and the tyrosine kinase oncogene cSRC. When a pollutant ligand binds to this complex, conformational changes dissemble the complex so that the ligand-AHR unit translocates into the nucleus where it dimerizes with ARNT. The ligand-AHR-ARNT entity induces transcription of target genes, specific for each xenobiotic ligand. Overstimulation by the ligand-AHR complex is prevented (1) by RNA transcription of the AHR repressor (AHRR) gene to synthesize co-repressors; and (2) by cytoplasmic degradation of the ligand-AHR entity after expulsion from the nucleus. After release from the initial cytoplasmic AHR complex, the chaperone protein oncogene cSRC binds to the epidermal growth factor receptor (EGFR), activating the cSRC protein kinase to induce carcinogenesis. (Modified from Figure 1 of Vogeley et al.^[47] with the author’s consent.). cSRC: “cellular sarcoma”, photo oncogene tyrosine-protein kinase; ARNT: AHR nuclear translocator