Proteasome affects the expression of aryl hydrocarbon receptor-regulated proteins

The effect of proteasome inhibition with N-acetyl-leucyl-leucyl-norleucinal (ALLN) on the protein expression regulated by aryl hydrocarbon receptor (AhR) was studied in T47D breast tumor cells. The luciferase reporter gene assay using a construct which has the xenobiotic responsive element showed that the inducible expression of the reporter with AhR ligands was significantly reduced by co-treatment with ALLN. The same suppressive effect by ALLN was observed for ethoxyresorufin O-deethylase (EROD) activity induced by an AhR ligand, 3-methylcholanthrene (3MC). Despite the above effects, the induced expression of CYP1A1 and CYP1B1 mRNAs was unaffected by ALLN. While lactacystin, another proteasome inhibitor, exhibited the same effect as ALLN on EROD activity induced by 3MC, leupeptin, which is one of the cysteine protease inhibitors, had no such effect. Based on the evidence obtained, it appears that proteasome inhibition results in a reduction in the expression of AhR-regulated proteins.