期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1982
卷号:79
期号:15
页码:4555-4559
DOI:10.1073/pnas.79.15.4555
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Specific inhibitors and anti-DNA polymerase alpha IgG have been utilized to probe for similarities between cytoplasmic rat hepatic glucocorticoid receptors and DNA polymerase alpha [DNA nucleotidyltransferase (DNA-directed), EC 2.7.7.7 ]. Rifamycin AF/013, an inhibitor of RNA and DNA polymerase activities, significantly inhibited the binding of activated [6,7-3H]-triamcinolone acetonide (TA) receptor complexes to DNA-cellulose. beta-Lapachone, an inhibitor of DNA polymerase alpha and reverse transcriptase activities, inhibited the specific binding of [6,7-3H]TA when preincubated with unbound receptors. Aphidicolin, another DNA polymerase alpha inhibitor, failed to inhibit any of the glucocorticoid-receptor functions tested. Two specific anti-DNA polymerase alpha IgGs interfered with glucocorticoid receptor functions as measured by their ability to inhibit the binding of [6,7-3H]TA to unbound receptors (85% maximal inhibition) and, to a lesser extent, to inhibit the binding of activated [6,7-3H]TA receptor complexes to DNA-cellulose (50% maximal inhibition). The anti-DNA polymerase alpha IgG and beta-lapachone failed to affect the binding of tritiated estradiol, progesterone, or 5 alpha-dihydrotestosterone to their receptors in appropriate rat target tissues or the binding of [1,2-3H]hydrocortisone to serum transcortin. The most obvious interpretation of these data is that cytoplasmic glucocorticoid receptors and DNA polymerase alpha share antigenic determinants. An alternative interpretation is that the polyclonal anti-DNA polymerase alpha antibody contains IgG molecules raised against calf thymus cytoplasmic activated glucocorticoid-receptor complexes that copurified with DNA polymerase alpha used as the antigen. Taken collectively, however, the antibody and inhibitor data suggest a relationship between DNA polymerase alpha and the glucocorticoid receptor.