Abstract
Bax is a pro-apoptotic member of Bcl-2 family proteins and is central to mitochondria-dependent apoptosis1,2,3. Bax resides in the cytosol as a quiescent protein and translocates into mitochondria after apoptotic stimuli4. Ku70 is a 70K subunit of the Ku complex, which has an important role in DNA double-strand break (DSB) repair in the nucleus5. In another article in this issue, we reported that Ku70 interacts with pro-apoptotic protein Bax in the cytosol and prevents its mitochondrial translocation6, 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.
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Supplementary Figures
Figure S1 Flow cytometric propidium iodide (PI) exclusion analysis. (PPT 402 kb)
Figure S2 Inhibitory effects of BIP against various apoptotic stimuli.
Figure S3 Optimization of Bax-plasmid transfection into Du145 cells.
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Sawada, M., Hayes, P. & Matsuyama, S. Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70. Nat Cell Biol 5, 352–357 (2003). https://doi.org/10.1038/ncb955
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DOI: https://doi.org/10.1038/ncb955
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