Figure 5.

Mechanism of negative feedback regulation of AhR function by AhRR. Ligand-activated AhR/Arnt heterodimer transactivates the expression of target genes (including AhRR gene) driven by the XRE sequence. ExpressedAhRRmRNA is translated into AhRR protein, and the resulting AhRR inhibits AhR function by competing with AhR for heterodimerizing with Arnt and binding with the XRE sequence. Consequently, inhibition of translation of AhRR mRNA by inhibitors of protein synthesis results in superinduction of mRNAs by TCDD or 3MC.