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Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70

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Article Details

Letter

Published: 24 March 2003

Authors

  • Motoshi Sawada
  • Paulette Hayes
  • Shigemi Matsuyama

Nature Cell Biology volume 5, pages 352–357 (2003)

  • 1687 Accesses
  • 141 Citations
  • 10 Altmetric

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.

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Acknowledgements

We thank D.A. Boothman for critical reviewing of the manuscript and encouragement. This work was supported in part by the Blood Center Research Foundation, Northwest Mutual Foundation, American Society of Hematology (Junior Faculty Award) to S.M.

Author information

Authors and Affiliations

The Blood Center of South Eastern Wisconsin and Department of Biochemistry, Blood Research Institute, Medical College of Wisconsin 8727, Watertown Plank Rd, Milwaukee, 53226, WI

Motoshi Sawada,Paulette Hayes&Shigemi Matsuyama