Protein synthesis-dependent and -independent induction of p69 2'-5'-oligoadenylate synthetase by interferon-alpha.
The 2'-5'-oligoadenylate (2-5A) synthetases are a family of interferon-alpha (IFN-alpha) inducible enzymes that block viral replication by activating a latent endonuclease during viral infections. In Ramos cells, induction of mRNAs for the intermediate isoform of 2-5A synthetase (p69) requires five-fold higher IFN-alpha than is required for induction of the small isoform (p40). The p40 and p69 isoforms are similarly induced between 1 and 24 h with maximal induction at 8 h. At 48 h, however, p69 is more strongly induced than p40. Induction of p69 and p40 between 1 and 24 h is protein synthesis independent whereas at 48 h, p69 induction becomes dependent on protein synthesis. Initial induction of both isoforms requires tyrosine kinase activation and is enhanced by activation of a separate signalling pathway by the tumour promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA). These data suggest that induction of the p40 is predominantly protein synthesis independent, whereas p69 induction occurs in two phases, an initial protein synthesis independent phase and a delayed protein synthesis dependent phase.
Yu
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F
Department of Biology, Arizona State University, Tempe, Arizona 85287-1501, USA.
Floyd-Smith
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G
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000235:genetics; D002051:Burkitt Lymphoma / Q000201:enzymology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008970:Molecular Weight; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D007527:Isoenzymes; D012333:RNA, Messenger; D003513:Cycloheximide; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D015088:2',5'-Oligoadenylate Synthetase; D013755:Tetradecanoylphorbol Acetate