A cell-permeable peptide inhibits activation of PKR and enhances cell proliferation.
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.
Nekhai
S
S
The Center for Cancer and Transplantation Biology, Children's National Medical Center, Washington, DC 20010, USA.
Bottaro
D P
DP
Woldehawariat
G
G
Spellerberg
A
A
Petryshyn
R
R
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability; D004789:Enzyme Activation / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D016325:HIV Long Terminal Repeat / Q000235:genetics; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016415:Sequence Alignment; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; D010446:Peptide Fragments; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D019892:eIF-2 Kinase