ATP promotes the appearance of two DNA-binding forms of the Ah receptor.
Following the binding of a specific ligand such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, mild heating has previously been shown to convert cytosolic aryl hydrocarbon (Ah) receptor to two DNA-binding forms: peak I, which appears to be an Ah receptor monomer; and peak II, which is larger and resembles nuclear Ah receptor. In rat liver cytosol pretreated with charcoal-dextran, and heated briefly at 22 degrees C, the addition of a physiological (3 mM) concentration of ATP substantially increases the formation of both peak I and peak II receptor. On more extended incubation in the presence of ATP most of the Ah receptor converts to the tighter binding peak II form. The ATP analog 5'-adenylylmethylene diphosphonate (AMPPCP) stimulates the appearance of both DNA-binding forms as effectively as ATP does. In cytosol separated from low molecular weight components by gel filtration prior to incubation, ATP substantially stimulates the appearance of peak II receptor. ATP also increases the amount of peak II receptor formed when peak I receptor is incubated with unlabeled charcoal-treated cytosol. Thus, ATP promotes both the release of Ah receptor monomer from the 9 S complex which cannot bind DNA and the subsequent conversion of that monomer to a form similar or identical to nuclear Ah receptor.
Cary
A J
AJ
Department of Biochemistry and Biophysics, University of Rhode Island, Kingston 02881.
Martin
P A
PA
Dougherty
J J
JJ
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000255:Adenosine Triphosphate; D004247:DNA; C002630:alpha,beta-methyleneadenosine 5'-triphosphate