Regulation of subcellular localization of the aryl hydrocarbon receptor (Ahr)

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription fac tor that mediates the toxicity of dioxin and other xenobiotics. In the abse nce of exogenous ligand, AhR is cytosolic. We investigated how AhR is retai ned in the cytosol and how dioxin induces AhR to move to the nucleus. Disru ption of nuclear export of AhR by the nuclear export inhibitor leptomycin B (LMB) or by mutation of the AhR nuclear export signal resulted in nuclear accumulation of AhR in the absence of exogenous ligand, Mutation of the AhR nuclear localization signal resulted in defects in nuclear import of AhR i n both the presence and the absence of exogenous ligand. Dioxin treatment c aused a more rapid accumulation of AhR in the nucleus than LMB treatment. I n the presence of both dioxin and LMB, nuclear accumulation of AhR was more rapid than in the presence of dioxin alone. Our results show that AhR shut tles between the nucleus and the cytosol in the absence of exogenous ligand . Binding of ligand induces an increase in the rate of nuclear import of Ah R but does not eliminate nuclear export of AhR, (C) 2001 Academic Press.