Double stranded RNA-dependent protein

Srivastava, S. P., Kumar, K. U., and Kaufman, R. J. (1998). Phosphorylation of eukaryotic translation initiation factor 2 mediates apoptosis in response to activation of the double-stranded RNA-dependent protein kinase. J. Biol. Chem. 273, 2416—2423. 

Page G, Rioux Bilan A, Ingrand S, Lafay-Chebassier C, Pain S, Perault Pochat MC, Bouras C, Bayer T, Hugon J (2006) Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer s disease. Neuroscience 139 1343-1354... 

Xu Z, WUliams BRG (2000) The B56a regulatory subunit of protein phosphatase 2 A is a target for regulation by double-stranded RNA-dependent protein kinase PKR. Mol CeU Biol 20 5285-5299... 

Morimoto, H. et al., Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2a pathway in human osteoblastic MG63 cells, J. Biochem., 136, 433, 2004. 

Johnson PA, MacLean C, Marsden HS, Dalziel RG, Everett RD (1986) The product of gene USll of herpes simplex virus type 1 is expressed as a true late gene. J Gen Virol 67 871 883 Kerr IM, Brown RE (1978) pppA2 p5 A2 p5 A an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci USA 75 256 260 Khabar KS, Dhalla M, Siddiqui Y, Zhou A, Al-Ahdal MN, Der SD, Silverman RH. Williams BR (2000) Effect of deficiency of the double-stranded RNA-dependent protein kinase, PKR, on antiviral resistance in the presence or absence of ribonuclease L HSV-1 replication is particularly sensitive to deficiency of the major IFN-mediated enzymes [In Process Citation]. J Interferon Cytokine Res 20 653-659... 

Kumar A, Haque J, Lacoste J, Hiscott J, Williams BR (1994) Double-stranded RNA-dependent protein kinase activates transcription factor NF-k B by phosphorylating I kappa B. Proc Natl Acad Sci USA 91 6288-6292... 

Desbarats J, Wade T, Wade WF, Newell MK (1999) Dichotomy between naive and memory CD4( + ) T cell responses to Fas engagement. Proc Natl Acad Sci USA 96 8104-8109 Dimitrov T, Krajcsi P, Hermiston TW, Tollefson AE, Hannink M, Wold WS (1997) Adenovirus E3-10.4K/14.5K protein complex inhibits tumor necrosis factor-induced translocation of cytosolic phospholipase A2 to membranes. J Virol 71 2830-2837 Donze O, Dostie J, Sonenberg N (1999) Regulatable expression of the interferon-induced double-stranded RNA dependent protein kinase PKR induces apoptosis and Fas receptor expression. Virology 256 322-329... 

Ito T, Yang M, May WS. RAX, a cellular aaivator for double-stranded RNA-dependent protein kinase during stress signaling. J Biol Chem 1999 274(22) 15427-15432. 

Romano PR, Zhang F, Tan SL et al. Inhibition of double-stranded RNA-dependent protein kinase PKR by vaccinia virus E3 role of complex formation and the E3 N-terminal domain. Mol Cell Biol 1998 18(12) 7304-7316. 

Yang LFR YL, Pavlovic J, Aguzzi A et al. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J 1995 14(24) 6095-6106. 

Jacobsen, H., Epstein, D. A., Friedmann, R. A., Safer, B., and Torrence, P. F., 1983, Double-stranded RNA-dependent phosphorylation of protein PI and eukaryotic initiation factor 2a does not correlate with protein synthesis inhibition in a cell-free system from interferon-treated mouse L cells, Proc. Natl. Acad. Sci. USA 80 41. 

Fig. 1.56. Control of eIF-2 by phosphorylation. Phosphorylated eIF-2 GDP binds strongly to eIF-2B without nucleotide exchange occurring. Initiation of protein biosynthesis is not possible in this case.In reticulocytes, eIF-2 is subject to phosphorylation by the heme-regulated eIF-2-kinase (HRI). The activity of the dimeric HRI is regulated via the heme concentration. Another protein kinase that can phosphorylate and regulate eIF-2 is the RNA-dependent eIF2a-kinase (PKR). The latter is induced by interferons and activated by double stranded RNA.

Short interfering RNA (siRNA) is a class of molecules composed of double-stranded RNA molecules (20-25 nucleotides) that are involved with the interference of specific genes (i.e., RNA interference or RNAi). During the RNAi process, the siRNA is incorporated into a protein complex, which unwinds the siRNA by an ATP-dependent mechanism to generate an... 

Double-stranded (ds) RNA-dependent protein kinase (PKR) was the first PRR shown to rect ise a product of viral replication, namely dsRNA. PKR is induced by IFN and in a critical host antiviral defence mechanism and as such it is both a PRR and an IFN eflFeaor protein. The discovery of PKR explained the observation that in cells pretreated with IFN, the translation ofviral mRNAs were blocked. - PKR is activated in response to viral, cellular or synthetic dsRNA of 30... 

Provided the synthesis of virus-specific RNA is dependent on the prior production of a virus-specific polymerase, RNA synthesis should be inhibited or abolished by the presence of inhibitors of protein synthesis. Protein synthesis in E, coli was more than 90% inhibited by either puromycin or chloramphenicol, and the fate of single-stranded RNA in E, coli investigated. The rate of conversion of viral RNA into double-stranded RNA was unaffected by chloramphenicol but was reduced to about half in the presence of puromycin. These results indicate that an RNA polymerase is already present in E, coli. 

Virus messenger RNA In order for the new virus-specific proteins to be made from the virus genome, it is necessary for new virus-specific RNA molecules to be made. Exactly how the virus brings about new mRNA synthesis depends upon the type of virus, and especially upon whether its genetic material is RNA or DNA, and whether it is single-stranded or double-stranded. Which copy is read into mRNA depends upon the location of the appropriate promoter, since the promoter points the direction that the RNA polymerase will follow. In cells (uninfected with virus) all mRNA is made on the DNA template, but with RNA viruses the situation is obviously different. 

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