Inhibition of double-stranded ribonucleic acid activated protein kinase and 2',5'-oligo(adenylic acid) polymerase by ethidium bromide.
The activation of two enzymes induced by interferon, a protein kinase and the 2',5'-oligo(adenylic acid) polymerase [2'5'-oligo(A) polymerase], is inhibited by ethidium bromide. The activation of these enzymes requires double-stranded RNA (dsRNA), and binding of ethidium to dsRNA inhibits the activation process. This was shown by determining the concentration of ethidium inhibitory for poly(A) . poly(U)- and poly(I) . poly(C)-activated reactions. Activation of both protein kinase and 2',5'-oligo(A) polymerase is inhibited by much lower concentrations of ethidium with the former polymer as activator than with the latter polymer. Correspondingly, in the presence of magnesium, ethidium binds with much greater affinity to poly(A) . poly(U) than to poly(I) . poly(C). Synthesis of 2',5'-oligo(A) with poly(A) . poly(U) as activator is arrested by adding low ethidium concentrations, but it is resumed upon addition of poly(I) . poly(C). Kinase activity, however, is not inhibited when ethidium is added after the activating dsRNA. This suggests that the kinase interacts with dsRNA in a manner different from the 2',5'-oligo(A) polymerase interaction.
D015088:2',5'-Oligoadenylate Synthetase; D004789:Enzyme Activation; D004996:Ethidium / Q000494:pharmacology*; D006367:HeLa Cells / Q000032:analysis; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D011063:Poly A-U / Q000378:metabolism; D011070:Poly I-C / Q000378:metabolism; D011118:Polynucleotide Ligases / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors; D012330:RNA, Double-Stranded / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D012330:RNA, Double-Stranded; D011063:Poly A-U; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D011118:Polynucleotide Ligases; D004996:Ethidium; D011070:Poly I-C