We found that Ku70, a known DNA repair factor, has a novel function to bind and inhibit Bax (Bcl-2-associated X protein), a key mediator of apoptosis. Pentapeptides derived from the Bax-binding domain of Ku70 were cell-permeable and protected cells from Bax-mediated apoptosis. These pentapeptides were called BIPs (Bax-inhibiting peptides). BIPs may become a useful therapeutic tool to reduce cellular damage. We also generated BIP mutant pentapeptides that do not inhibit Bax, but retain their cell-penetrating activity. Since both BIPs and BIP mutants are cell-permeable, these peptides were designated CPP5s (cell-penetrating pentapeptides). Among the CPP5s discovered, VPTLK (BIP) and KLPVM (BIP mutant) were confirmed to possess protein transduction activity by examination of the delivery of GFP (green fluorescent protein) into cells by these peptides. The mechanism of cell penetration by CPP5s is not known. CPP5s enter the cell at 0 and 4°C. In preliminary studies, various inhibitors of endocytosis and pinocytosis did not show any significant suppression of CPP5 cell entry. CPP5s have very low toxicity in vitro and in vivo and so may be useful tools in order to develop non-toxic drug-delivery technologies.
Skip Nav Destination
Article navigation
August 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
July 20 2007
Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides
J.A. Gomez;
J.A. Gomez
*Pharmacology Department, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
Search for other works by this author on:
V. Gama;
V. Gama
*Pharmacology Department, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
Search for other works by this author on:
T. Yoshida;
T. Yoshida
†Laboratory of Animal Reproduction, Graduate School of Agricultural Sciences, Tohoku University, Japan
Search for other works by this author on:
W. Sun;
W. Sun
‡Sankyo Pharmaceutical Co. Ltd, Tokyo, Japan
Search for other works by this author on:
P. Hayes;
P. Hayes
§Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, U.S.A.
Search for other works by this author on:
K. Leskov;
K. Leskov
∥Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
Search for other works by this author on:
D. Boothman;
D. Boothman
¶Department of Pharmacology, Program in Cell Stress and Cancer Nanomedicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, U.S.A.
Search for other works by this author on:
S. Matsuyama
S. Matsuyama
1
*Pharmacology Department, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
**Division of Hematology and Oncology, School of Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
1To whom correspondence should be addressed (email shigemi.matsuyama@case.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
April 25 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 797–801.
Article history
Received:
April 25 2007
Citation
J.A. Gomez, V. Gama, T. Yoshida, W. Sun, P. Hayes, K. Leskov, D. Boothman, S. Matsuyama; Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. Biochem Soc Trans 1 August 2007; 35 (4): 797–801. doi: https://doi.org/10.1042/BST0350797
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.