Scientific background: |
EIF2AK2 (Eukaryotic Translation Initiation Factor 2-Alpha Kinase 2), also called PKR, is an enzyme that in humans is encoded by the EIF2AK2 gene. Activation of EIF2AK2 allows the kinase to phosphorylate its natural substrate, the alpha subunit of eukaryotic protein synthesis initiation factor-2, leading to the inhibition of protein synthesis (summary by Kuhen et al., 1996). By FISH analysis, Squire et al. (1993) assigned the EIF2AK2 gene to the boundary between chromosome 2p22-p21. Ben-Asouli et al. (2002) showed that human gamma-interferon mRNA uses local activation of PKR in the cell to control its own translation yield. IFNG mRNA was found to activate PKR through a pseudoknot in its 5-prime untranslated region. Taylor et al. (1999) studied the mechanism underlying the resistance of hepatitis C virus (HCV) to interferon. They demonstrated that the HCV envelope protein E2 contains a sequence identical with phosphorylation sites of the interferon-inducible protein kinase PKR and the translation initiation factor EIF2-alpha, a target of PKR. E2 inhibited the kinase activity of PKR and blocked its inhibitory effect on protein synthesis and cell growth. |
References: |
1. Ben-Asouli, Y., Banai, Y., Pel-Or, Y., Shir, A., Kaempfer, R. Human interferon-gamma mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR. Cell 108: 221-232, 2002.
2. Kuhen, K. L., Shen, X., Carlisle, E. R., Richardson, A.L., Weier, H.-U. G., Tanaka, H., Samuel, C. E. Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-dependent protein kinase (PKR) and differences from its mouse homolog. Genomics 36: 197-201, 1996.
3. Squire, J., Meurs, E. F., Chong, K. L., McMillan, N. A. J., Hovanessian, A. G., Williams, B. R. G. Localization of the human interferon-induced, ds-RNA activated p68 kinase gene (PRKR) to chromosome 2p21-p22. Genomics 16: 768-770, 1993.
4. Taylor, D. R., Shi, S. T., Romano, P. R., Barber, G. N., Lal, M. M. C. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 285: 107-110, 1999.
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