Inhibition of the specific DNA binding activity of the dioxin receptor by phosphatase treatment.
1991; Elsevier BV; Volume: 266; Issue: 25 Linguagem: Inglês
10.1016/s0021-9258(18)55374-6
ISSN1083-351X
AutoresIngemar Pongratz, P E Strömstedt, Grant Mason, Lorenz Poellinger,
Tópico(s)Carcinogens and Genotoxicity Assessment
ResumoThe dioxin receptor stimulates transcription of the cytochrome P-450IA1 gene in response to dioxin. Exposure of the intracellular dioxin receptor to dioxin leads to a rapid conversion of the receptor from a latent form to a DNA binding species which specifically recognizes dioxin-responsive positive control elements in vitro. In this report, we show that treatment of in vivo or in vitro ligand-activated receptor with potato acid phosphatase significantly reduced or abolished its specific DNA binding activity. This effect was inhibited in the presence of sodium phosphate. In control experiments, the ligand-activated glucocorticoid receptor was not inactivated by phosphatase treatment. Moreover, phosphatase treatment did not induce any detectable degradation of covalently labeled dioxin receptor, arguing against protease contamination as a cause for receptor inactivation. Finally, phosphatase-inactivated dioxin receptor exhibited bona fide levels of ligand binding activity. Taken together, these data suggest that phosphorylation may regulate the DNA binding activity of the ligand-occupied dioxin receptor.
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