Abstract
The double-stranded RNA dependent protein kinase (PKR) is a negative regulator of cell proliferation and thus itself a target for modulation. We show that a cell-permeable peptide (PRI), containing a conserved double-stranded RNA binding motif found in PKR, inhibits activation of the kinase and activity to phosphorylate its substrate. Further, the PRI-peptide localizes to the cytoplasm of murine embryonic fibroblasts and ablates cellular PKR activation. The PRI-peptide enhances cell proliferation compared to treatment with a variant control peptide, resulting in cultures with increased cell density. We conclude that peptides that interfere with PKR may be useful tools for regulating cell proliferation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Cell Division / drug effects
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Cell Membrane Permeability
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Enzyme Activation / drug effects
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Eukaryotic Initiation Factor-2 / metabolism
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Fluorescent Antibody Technique, Indirect
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HIV Long Terminal Repeat / genetics
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Humans
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Kinetics
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Mice
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Molecular Sequence Data
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Peptide Fragments / administration & dosage
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology*
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Phosphorylation / drug effects
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Protein Binding
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Protein Structure, Tertiary
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RNA, Viral / metabolism
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RNA-Binding Proteins / administration & dosage
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / metabolism
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RNA-Binding Proteins / pharmacology
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Sequence Alignment
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eIF-2 Kinase / antagonists & inhibitors*
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eIF-2 Kinase / metabolism
Substances
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Eukaryotic Initiation Factor-2
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Peptide Fragments
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RNA, Viral
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RNA-Binding Proteins
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eIF-2 Kinase