Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70.
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.
Sawada
Motoshi
M
Blood Research Institute, The Blood Center of South Eastern Wisconsin and Department of Biochemistry, Medical College of Wisconsin 8727 Watertown Plank Rd, Milwaukee WI 53226, USA.
Hayes
Paulette
P
Matsuyama
Shigemi
S
D000595:Amino Acid Sequence / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000235:genetics; D003451:Cryoprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; D029681:Arabidopsis Proteins; C494826:BAX protein, human; D003451:Cryoprotective Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C463462:KU70 protein, Arabidopsis; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein