title: Tipping the balance: antagonism of PKR kinase and ADAR1 deaminase functions by virus gene products.
abstract: The protein kinase regulated by RNA (PKR) and the adenosine deaminase acting on RNA (ADAR1) are interferon-inducible enzymes that play important roles in biologic processes including the antiviral actions of interferons, signal transduction, and apoptosis. PKR catalyzes the RNA-dependent phosphorylation of protein synthesis initiation factor eIF-2 alpha, thereby leading to altered translational patterns in interferon-treated and virus-infected cells. PKR also modulates signal transduction responses, including the induction of interferon. ADAR1 catalyzes the deamination of adenosine (A) to generate inosine (I) in RNAs with double-stranded character. Because I is recognized as G instead of A, A-to-I editing by ADAR1 can lead to genetic recoding and altered RNA structures. The importance of PKR and ADAR1 in innate antiviral immunity is illustrated by a number of viruses that encode either RNA or protein viral gene products that antagonize PKR and ADAR1 enzymatic activity, localization, or stability.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
authors.forename: Cyril X
authors.initials: CX
authors.lastname: George
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Li
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Okonski
authors.forename: Ann M
authors.initials: AM
authors.lastname: Toth
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Charles E
authors.initials: CE
authors.lastname: Samuel
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D004791:Enzyme Inhibitors / Q000276:immunology / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology; D017393:RNA Editing; D012327:RNA Virus Infections / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D012328:RNA Viruses / Q000472:pathogenicity / Q000502:physiology*; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D007372:Interferons; D019892:eIF-2 Kinase; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase