A cell-permeable peptide inhibits activation of PKR and enhances cell proliferation |
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Authors: | Nekhai S Bottaro D P Woldehawariat G Spellerberg A Petryshyn R |
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Institution: | The Center for Cancer and Transplantation Biology, Children's National Medical Center, Washington, DC 20010, USA. |
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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. |
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