PACT, a protein activator of the interferon-induced protein kinase, PKR.
PKR, a latent protein kinase, mediates the antiviral actions of interferon. It is also involved in cellular signal transduction, apoptosis, growth regulation and differentiation. Although in virus-infected cells, viral double-stranded (ds) RNA can serve as a PKR activator, cellular activators have remained obscure. Here, we report the cloning of PACT, a cellular protein activator of PKR. PACT heterodimerized with PKR and activated it in vitro in the absence of dsRNA. In mammalian cells, overexpression of PACT caused PKR activation and, in yeast, co-expression of PACT enhanced the anti-growth effect of PKR. Thus, PACT has the hallmarks of a direct activator of PKR.
Department of Molecular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, OH 44195, USA.
R C
RC
Patel
G C
GC
Sen
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003001:Cloning, Molecular; D019281:Dimerization; D004789:Enzyme Activation / Q000235:genetics; D004790:Enzyme Induction / Q000235:genetics; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005822:Genetic Vectors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D019892:eIF-2 Kinase / Q000096:biosynthesis* / Q000378:metabolism*
D002352:Carrier Proteins; D015852:Eukaryotic Initiation Factor-2; C104647:PRKRA protein, human; D016601:RNA-Binding Proteins; D007372:Interferons; D019892:eIF-2 Kinase