A cell-permeable peptide inhibits activation of PKR and enhances cell proliferation

Peptides. 2000 Oct;21(10):1449-56. doi: 10.1016/s0196-9781(00)00297-7.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Cell Division / drug effects
  • Cell Membrane Permeability
  • Enzyme Activation / drug effects
  • Eukaryotic Initiation Factor-2 / metabolism
  • Fluorescent Antibody Technique, Indirect
  • HIV Long Terminal Repeat / genetics
  • Humans
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Phosphorylation / drug effects
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / administration & dosage
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / pharmacology
  • Sequence Alignment
  • eIF-2 Kinase / antagonists & inhibitors*
  • eIF-2 Kinase / metabolism

Substances

  • Eukaryotic Initiation Factor-2
  • Peptide Fragments
  • RNA, Viral
  • RNA-Binding Proteins
  • eIF-2 Kinase