A novel response to dioxin. Induction of ecto-ATPase gene expression.
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.
Gao
L
L
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-5332, USA.
Dong
L
L
Whitlock
J P
JP
D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007526:Isoelectric Point; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000072317:Polychlorinated Dibenzodioxins; D019363:Cytochrome P-450 CYP1A1; D000251:Adenosine Triphosphatases; C027201:ectoATPase