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  • Title: Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70.
    Author: Sawada M, Hayes P, Matsuyama S.
    Journal: Nat Cell Biol; 2003 Apr; 5(4):352-7. PubMed ID: 12652309.
    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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