Dioxin suppresses the checkpoint protein, MAD2, by an aryl hydrocarbon receptor-independent pathway

The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown rece ntly to be carcinogenic, but little is currently known about the molecular mechanism of TCDD affecting cell proliferation and carcinogenesis. In this report, we demonstrate that TCDD suppresses the expression of the checkpoin t protein, Mad2. Suppression of Mad2 was also observed in aryl hydrocarbon receptor-deficient mouse embryonic fibroblasts, suggesting that TCDD suppre sses Mad2 by a novel TCDD receptor signaling mechanism. In addition, HeLa c ells treated with TCDD failed to arrest in mitosis after nocodazole treatme nt. The Mad2 protein plays a significant role in accurate chromosome segreg ation in mitotic cells. Our data suggest that TCDD may increase chromosomal instability through the suppression of Mad2 expression.