Repression of glucocorticoid receptor function by the anti-rheumatic gold compound aurothiomalate.
We describe functional interaction between the anti-rheumatic water-soluble gold compound aurothiomalate and glucocorticoid receptors. Aurothiomalate contains gold in the Au(I) state, and Au(I) alone, not thiomalate or malate, reduced the ligand-binding activity of the glucocorticoid receptor. Au(I) also interfered with the productive interaction between the glucocorticoid receptor and the cognate target DNA sequences and repressed the transactivation function of the receptor. Thus, Au(I) variably modulates glucocorticoid receptor-mediated intracellular signals.
Makino
Y
Y
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Tanaka
H
H
Hirano
F
F
Fukawa
E
E
Makino
I
I
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism; D005822:Genetic Vectors; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D007700:Kinetics; D008324:Mammary Tumor Virus, Mouse; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011965:Receptors, Glucocorticoid; D006052:Gold Sodium Thiomalate; D003907:Dexamethasone; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase