Bax-inhibiting peptide derived from mouse and rat Ku70.
Bax is a proapoptotic protein that plays a key role in the induction of apoptosis. Ku70 has activities to repair DNA damage in the nucleus and to suppress apoptosis by inhibiting Bax in the cytosol. We previously designed peptides based on the amino acid sequence of Bax-binding domain of human Ku70, and showed that these peptides bind Bax and inhibit cell death in human cell lines. In the present report, we examined the biological activities of other pentapeptides, VPTLK and VPALR, derived from mouse and rat Ku70. Cells in culture accumulated FITC-labeled VPTLK and VPALR, indicating that these peptides are cell permeable (human, mouse, rat, and porcine cells were examined). These peptides bound to Bax and suppressed cell death in various cell types including primary cultured cells. These data suggest that such Bax inhibiting peptides from three mammalian species may be used to protect healthy cells from apoptotic injury under pathological conditions.
Yoshida
Tomoyuki
T
Blood Research Institute, The Blood Center of South Eastern Wisconsin and Department of Biochemistry, Medical College of Wisconsin, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA.
Tomioka
Ikuo
I
Nagahara
Takako
T
Holyst
Trudy
T
Sawada
Motoshi
M
Hayes
Paulette
P
Gama
Vivian
V
Okuno
Misako
M
Chen
Yuhong
Y
Abe
Yasuyuki
Y
Kanouchi
Tadashi
T
Sasada
Hiroshi
H
Wang
Demin
D
Yokota
Takanori
T
Sato
Eimei
E
Matsuyama
Shigemi
S
D000595:Amino Acid Sequence; D000818:Animals; D034961:Antigens, Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017386:Sequence Homology, Amino Acid; D051028:bcl-2-Associated X Protein
D034961:Antigens, Nuclear; C494826:BAX protein, human; C494827:Bax protein, mouse; C494828:Bax protein, rat; D004268:DNA-Binding Proteins; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D005047:Etoposide; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen