Figure 3

AhR ligand-mediated activation of phase I and II metabolizing enzyme genes. The diagram represents a basic model of the molecular events following the entry of an AhR ligand, such as TCDD, in the cell. Upon ligand binding the AhR complex dissociates with XAP2, p23 and HSP90 proteins and translocates to the nucleus. Nuclear import is inhibited by phosphorylation reactions of either Ser-12 or Ser-36 residues of the Nuclear localization signal (NLS), while phosphorylation of phosphotyrosine residues in the carboxy terminal of the AhR is required for the formation of a functional AhR/ARNT complex [19]. Binding of the AhR/ARNT complex to XRE is inhibited by the ARNT/AhRR dimer. Initiation of the transcription of genes encoding for phase I and phase II metabolizing enzymes occurs via the interaction of several transcription factors such as Sp1 and co-activators such as p-300 and p/CIP, which eventually leads to binding with TBP (TATA binding protein) and subsequent recruitment of RNA polymerase II [20–22]. There is a great number of other transcription factors, co-activators and general transcription factors (GTFs) involved in this process, which are not shown for clarity.