Cytoprotective Membrane-Permeable Peptides Designed From the Bax-binding Domain of Ku70

Nat Cell Biol. 2003 Apr;5(4):352-7. doi: 10.1038/ncb955.

Abstract

Bax is a pro-apoptotic member of Bcl-2 family proteins and is central to mitochondria-dependent apoptosis. Bax resides in the cytosol as a quiescent protein and translocates into mitochondria after apoptotic stimuli. Ku70 is a 70K subunit of the Ku complex, which has an important role in DNA double-strand break (DSB) repair in the nucleus. In another article in this issue, we reported that Ku70 interacts with pro-apoptotic protein Bax in the cytosol and prevents its mitochondrial translocation, suggesting that Ku70 suppresses Bax-mediated apoptosis. Here, we describe the development of a new membrane-permeable peptide, Bax-inhibiting peptide (BIP) that inhibits Bax-mediated apoptosis, on the basis of the previous finding that showed an interaction between Ku70 and Bax. BIP is comprised of five amino acids designed from the Bax-binding domain of Ku70, and suppresses the mitochondrial translocation of Bax. BIP inhibited Bax-mediated apoptosis induced by staurosporine, UVC irradiation and anti-cancer drugs in several types of cells. BIP may provide valuable information in the development of therapeutics that control apoptosis-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Amino Acid Sequence / genetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Binding Sites / drug effects
  • Binding Sites / genetics
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / genetics
  • Cryoprotective Agents / chemical synthesis
  • Cryoprotective Agents / pharmacology
  • Cryoprotective Agents / therapeutic use
  • Cytosol / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Eukaryotic Cells / metabolism*
  • HeLa Cells
  • Humans
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use
  • Protein Structure, Tertiary / drug effects
  • Protein Structure, Tertiary / genetics
  • Protein Transport / drug effects
  • Protein Transport / genetics*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2*
  • bcl-2-Associated X Protein

Substances

  • Antineoplastic Agents
  • Arabidopsis Proteins
  • BAX protein, human
  • Cryoprotective Agents
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • KU70 protein, Arabidopsis
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein