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

研究成果: Article

21 引用 (Scopus)

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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.

元の言語English
ページ(範囲)613-620
ページ数8
ジャーナルMolecular Pharmacology
83
発行部数3
DOI
出版物ステータスPublished - 2013 3 1
外部発表Yes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

これを引用

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, 83(3), 613-620. https://doi.org/10.1124/mol.112.082602