Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides

J. A. Gomez, V. Gama, T. Yoshida, W. Sun, P. Hayes, K. Leskov, D. Boothman, S. Matsuyama

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)797-801
Number of pages5
JournalBiochemical Society Transactions
Volume35
Issue number4
StatePublished - Aug 2007

Fingerprint

bcl-2-Associated X Protein
Peptides
Apoptosis
Green Fluorescent Proteins
Drug delivery
Pinocytosis
Toxicity
BIP Bax-inhibiting peptide
Repair
Endocytosis
Protein Binding
DNA Repair
DNA
Technology
Proteins

Keywords

  • Bax-inhibiting peptide (BIP)
  • Cell-penetrating peptide (CPP)
  • Drug delivery
  • Pentapeptide

ASJC Scopus subject areas

  • Biochemistry

Cite this

Gomez, J. A., Gama, V., Yoshida, T., Sun, W., Hayes, P., Leskov, K., ... Matsuyama, S. (2007). Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. Biochemical Society Transactions, 35(4), 797-801.

Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. / Gomez, J. A.; Gama, V.; Yoshida, T.; Sun, W.; Hayes, P.; Leskov, K.; Boothman, D.; Matsuyama, S.

In: Biochemical Society Transactions, Vol. 35, No. 4, 08.2007, p. 797-801.

Research output: Contribution to journalArticle

Gomez, JA, Gama, V, Yoshida, T, Sun, W, Hayes, P, Leskov, K, Boothman, D & Matsuyama, S 2007, 'Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides', Biochemical Society Transactions, vol. 35, no. 4, pp. 797-801.
Gomez JA, Gama V, Yoshida T, Sun W, Hayes P, Leskov K et al. Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. Biochemical Society Transactions. 2007 Aug;35(4):797-801.
Gomez, J. A. ; Gama, V. ; Yoshida, T. ; Sun, W. ; Hayes, P. ; Leskov, K. ; Boothman, D. ; Matsuyama, S. / Bax-inhibiting peptides derived from Ku70 and cell-penetrating pentapeptides. In: Biochemical Society Transactions. 2007 ; Vol. 35, No. 4. pp. 797-801.
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