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J Biol Chem, Vol. 273, Issue 25, 15358-15365, June 19, 1998
From the Department of Molecular Pharmacology, Stanford University
School of Medicine, Stanford, California 94305-5332
We used differential display to discover a new
gene that the environmental contaminant
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) regulates in
mouse hepatoma cells. Its predicted amino acid sequence suggests that
the gene encodes an ecto-ATPase that contains multiple glycosylation
sites, conserved cysteine residues, and apyrase conserved regions.
cDNA expression experiments in mouse hepatoma cells confirm that
the new gene encodes an ecto-ATPase. Wild-type mouse hepatoma cells
contain both constitutive and TCDD-inducible ecto-ATPase activity.
Induction of ecto-ATPase gene expression by TCDD is direct and
occurs at the transcriptional level. Studies in mutant hepatoma cells
indicate that induction requires both the aromatic hydrocarbon
receptor (AhR) and the AhR nuclear translocator (Arnt). Furthermore,
induction requires AhR's transactivation domain, but not that of
Arnt. Our findings reveal new aspects of dioxin's biological effects
and TCDD-dependent gene regulation.
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