FIG. 9.
Proposed model for AhR-mediated degradation of ERα through activation of the proteasome pathway. Cytosolic AhR is activated by TCDD ligand, which induces disassociation of the heat shock protein 90 (hsp 90), AhR-interacting protein (AIP), and pp60Src kinase complex. Activated AhR translocates to the nucleus, which enables direct interaction with nuclear ERα, subsequent ubiquitination, and proteolysis by the 26S proteasome complex. Both ERα ubiquitination and proteolysis are increased in cells cotreated with ET. E alone induces degradation of nuclear ERα but not the cytosolic AhR, and this may be due to lack of receptor colocalization.