A Novel Response to Dioxin
INDUCTION OF ECTO-ATPase GENE EXPRESSION*
- From the Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-5332
Abstract
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.
Footnotes
-
↵* This work was supported by National Institutes of Health Grant ES03719 (to J. P. W.) and a Pharmaceutical Research and Manufacturers of America Foundation (PhRMA) Fellowship for Advanced Predoctoral Training in Pharmacology/Toxicology (to L. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) .
-
↵‡ To whom correspondence should be addressed. Tel.: 650-723-8233; Fax: 650-725-2952.
-
↵1 The abbreviations used are: TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; ACR, apyrase conserved regions; AhR, aromatic hydrocarbon receptor; Arnt, Ah receptor nuclear translocator; DIG, digoxigenin; PAS, a homologous region shared by Per, Arnt, and Sim.
-
↵2 L. Gao and J. P. Whitlock, Jr., unpublished results.
-
- Received February 6, 1998.
- Revision received April 2, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
