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 recently 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 checkpoint protein, Mad2. Suppression of Mad2 was also observed in aryl hydrocarbon receptor-deficient mouse embryonic fibroblasts, suggesting that TCDD suppresses Mad2 by a novel TCDD receptor signaling mechanism. In addition, HeLa cells treated with TCDD failed to arrest in mitosis after nocodazole treatment. The Mad2 protein plays a significant role in accurate chromosome segregation in mitotic cells. Our data suggest that TCDD may increase chromosomal instability through the suppression of Mad2 expression.
Oikawa
K
K
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 160-8402, Japan.
Ohbayashi
T
T
Mimura
J
J
Iwata
R
R
Kameta
A
A
Evine
K
K
Iwaya
K
K
Fujii-Kuriyama
Y
Y
Kuroda
M
M
Mukai
K
K
D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins; D003433:Crosses, Genetic; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D006367:HeLa Cells; D006801:Humans; D064246:Mad2 Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects / Q000502:physiology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins
D002135:Calcium-Binding Proteins; D002274:Carcinogens, Environmental; D018797:Cell Cycle Proteins; D004785:Environmental Pollutants; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins