title: A dominant negative mutant of 2-5A-dependent RNase suppresses antiproliferative and antiviral effects of interferon.
abstract: 2-5A-dependent RNase is the terminal factor in the interferon-regulated 2-5A system thought to function in both the molecular mechanism of interferon action and in the general control of RNA stability. However, direct evidence for specific functions of 2-5A-dependent RNase has been generally lacking. Therefore, we developed a strategy to block the 2-5A system using a truncated form of 2-5A-dependent RNase which retains 2-5A binding activity while lacking RNase activity. When the truncated RNase was stably expressed to high levels in murine cells, it prevented specific rRNA cleavage in response to 2-5A transfection and the cells were unresponsive to the antiviral activity of interferon alpha/beta for encephalomyocarditis virus. Remarkably, cells expressing the truncated RNase were also resistant to the antiproliferative activity of interferon. The truncated RNase is a dominant negative mutant that binds 2-5A and that may interfere with normal protein-protein interactions through nine ankyrin-like repeats.
authors.affiliation: Department of Cancer Biology, Cleveland Clinic Foundation, OH 44195.
authors.forename: B A
authors.initials: BA
authors.lastname: Hassel
authors.forename: A
authors.initials: A
authors.lastname: Zhou
authors.forename: C
authors.initials: C
authors.lastname: Sotomayor
authors.forename: A
authors.initials: A
authors.lastname: Maran
authors.forename: R H
authors.initials: RH
authors.lastname: Silverman
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004686:Encephalomyocarditis virus / Q000276:immunology; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D004790:Enzyme Induction; D005799:Genes, Dominant; D006801:Humans; D007372:Interferons / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011494:Protein Kinases / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014779:Virus Replication
chemical_list: D007372:Interferons; D011494:Protein Kinases; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease