Vitamin K2 covalently binds to bak and induces bak-mediated apoptosiss

Satoki Karasawa, Motoki Azuma, Takeshi Kasama, Satoshi Sakamoto, Yasuaki Kabe, Takeshi Imai, Yuki Yamaguchi, Keisuke Miyazawa, Hiroshi Handa

Research output: Contribution to journalArticle

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Abstract

Vitamin K2 (VK2, menaquinone) is known to have anticancer activity in vitro and in vivo. Although its effect is thought to be mediated, at least in part, by the induction of apoptosis, the underlying molecular mechanism remains elusive. Here, we identified Bcl-2 antagonist killer 1 (Bak) as a molecular target of VK2-induced apoptosis. VK2 directly interacts with Bak and induces mitochondrial-mediated apoptosis. Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for VK2-induced cytochrome c (cyt c) release and cell death. Moreover, VK2-2,3 epoxide, an intracellular metabolite of VK2, was shown to covalently bind to the cysteine-166 residue of Bak. Several lines of evidence suggested that the covalent attachment of VK2 is critical for apoptosis induction. Thus this study reveals a specific role for Bak in mitochondria-mediated apoptosis. This study also provides insight into the anticancer effects of VK2 and suggests that Bak may be a potential target of cancer therapy.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalMolecular Pharmacology
Volume83
Issue number3
DOIs
Publication statusPublished - 2013 Mar
Externally publishedYes

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Vitamin K 2
Apoptosis
bcl-2-Associated X Protein
Epoxy Compounds
Cytochromes c
Cysteine
Mitochondria
Cell Death
Neoplasms

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Karasawa, S., Azuma, M., Kasama, T., Sakamoto, S., Kabe, Y., Imai, T., ... Handa, H. (2013). Vitamin K2 covalently binds to bak and induces bak-mediated apoptosiss. Molecular Pharmacology, 83(3), 613-620. https://doi.org/10.1124/mol.112.082602

Vitamin K2 covalently binds to bak and induces bak-mediated apoptosiss. / Karasawa, Satoki; Azuma, Motoki; Kasama, Takeshi; Sakamoto, Satoshi; Kabe, Yasuaki; Imai, Takeshi; Yamaguchi, Yuki; Miyazawa, Keisuke; Handa, Hiroshi.

In: Molecular Pharmacology, Vol. 83, No. 3, 03.2013, p. 613-620.

Research output: Contribution to journalArticle

Karasawa, S, Azuma, M, Kasama, T, Sakamoto, S, Kabe, Y, Imai, T, Yamaguchi, Y, Miyazawa, K & Handa, H 2013, 'Vitamin K2 covalently binds to bak and induces bak-mediated apoptosiss', Molecular Pharmacology, vol. 83, no. 3, pp. 613-620. https://doi.org/10.1124/mol.112.082602
Karasawa, Satoki ; Azuma, Motoki ; Kasama, Takeshi ; Sakamoto, Satoshi ; Kabe, Yasuaki ; Imai, Takeshi ; Yamaguchi, Yuki ; Miyazawa, Keisuke ; Handa, Hiroshi. / Vitamin K2 covalently binds to bak and induces bak-mediated apoptosiss. In: Molecular Pharmacology. 2013 ; Vol. 83, No. 3. pp. 613-620.
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