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Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein.
It is reported that NS5A represses PKR through a direct interaction with the protein kinase catalytic domain and that both PKR repression and interaction requires the ISDR, suggesting inactivation of PKR may be one mechanism by which HCV avoids the antiviral effects of IFN. Expand
Phosphorylation of initiation factor 2α by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast
- T. E. Dever, Lan Feng, R. Wek, A. Cigan, T. Donahue, A. Hinnebusch
- Medicine, Biology
- 7 February 1992
An established mechanism for regulating total protein synthesis in mammalian cells mediates gene-specific translational control in yeast through phosphorylation of the alpha subunit of eIF-2 by the protein kinase GCN2. Expand
The elongation, termination, and recycling phases of translation in eukaryotes.
This work summarizes the current understanding of the elongation and termination/recycling phases of eukaryotic protein synthesis and presents some of the key questions in translation elongation, termination, and recycling that remain to be answered. Expand
Structure of the Dual Enzyme Ire1 Reveals the Basis for Catalysis and Regulation in Nonconventional RNA Splicing
- K. Lee, Madhusudan Dey, D. Neculai, C. Cao, T. E. Dever, F. Sicheri
- Biology, Medicine
- 11 January 2008
It is shown that signal induced trans-autophosphorylation of the kinase domain permits unfettered binding of nucleotide, which in turn promotes dimerization to compose the ribonuclease active site, which provides a basis for understanding the mechanism of action of RNaseL and other pseudokinases. Expand
Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation.
- K. Frerichs, C. B. Smith, +5 authors J. Hallenbeck
- Medicine, Biology
- Proceedings of the National Academy of Sciences…
- 24 November 1998
Findings implicate suppression of PS as a component of the regulated shutdown of cellular function that permits hibernating ground squirrels to tolerate "trickle" blood flow and reduced substrate and oxygen availability. Expand
Gene-Specific Regulation by General Translation Factors
- T. E. Dever
- Biology, Medicine
- 22 February 2002
This work has helped elucidate how modifications of the general translational machinery regulate gene-specific protein production and enables cells to rapidly manipulate protein production without new mRNA synthesis, processing, or export. Expand
Higher-Order Substrate Recognition of eIF2α by the RNA-Dependent Protein Kinase PKR
X-ray crystal structures of the catalytic domain of PKR in complex with eif2alpha reveal that eIF2alpha binds to the C-terminal catalytic lobe while catalytic-domain dimerization is mediated by the N-terminals, and the generality and implications of the structural mechanisms uncovered for PKR to the larger family of four human eIF1alpha protein kinases are discussed. Expand
eIF5A promotes translation of polyproline motifs.
EIF5A, like its bacterial ortholog EFP, is proposed to stimulate the peptidyl transferase activity of the ribosome and facilitate the reactivity of poor substrates like Pro. Expand
Mechanistic Link between PKR Dimerization, Autophosphorylation, and eIF2α Substrate Recognition
An ordered mechanism of PKR activation is proposed in which catalytic-domain dimerization triggers Thr446 autophosphorylation and specific eIF2alpha substrate recognition. Expand
Hypusine-containing Protein eIF5A Promotes Translation Elongation
Molecular genetic and biochemical studies are used to show that eIF5A promotes translation elongation, and suggest that it might function together with eEF2 to promote ribosomal translocation. Expand