title: Peptides derived from the interferon-induced PKR prevent activation by HIV-1 TAR RNA.
abstract: The double-stranded RNA-dependent protein kinase (PKR) is believed to mediate cellular antiviral responses, function as a tumor suppressor, and regulate cell growth and differentiation. Its activation is dependent on double-stranded RNA (dsRNA) structures but these interactions are not fully understood. The possibility of direct interaction between dsRNA and the arginine and lysine-rich region of PKR (residues 54-74) was examined using synthetic peptides. We found that addition of a synthetic peptide corresponding to residues 54-74 of murine PKR or residues 60-80 of human PKR inhibited the autophosphorylation and activation of the kinase by either poly(I)-poly(C) or the 82-nucleotide-long TAR RNA. Gel-shift analysis indicated that the peptides disrupted the kinase-TAR complex by binding directly to TAR RNA. These findings delineate at least one dsRNA-binding domain in PKR which may be important for its cellular activation.
authors.affiliation: Center for Cancer and Transplantation Biology, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nekhai
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: D P
authors.initials: DP
authors.lastname: Bottaro
authors.forename: R
authors.initials: R
authors.lastname: Petryshyn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D019892:eIF-2 Kinase
chemical_list: D010455:Peptides; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase