A novel apoptosis-inducing protein from Helicobacter pylori

Keigo Shibayama, Kazunari Kamachi, Noriyo Nagata, Tetsuya Yagi, Toshi Nada, Yohei Doi, Naohiro Shibata, Keiko Yokoyama, Kunikazu Yamane, Haru Kato, Yoshitsugu Iinuma, Yoshichika Arakawa

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Abstract

Helicobacter pylori infection induces apoptosis in gastric epithelial cells. Here, we report a novel apoptosis-inducing protein that functions as a leading factor in H. pylori-mediated apoptosis induction. We purified the protein from H. pylori by separating fractions that showed apoptosis-inducing activity. This protein induced apoptosis of AGS cells in a dose-dependent manner. The purified protein consisted of two protein fragments with molecular masses of about 40 and 22 kDa, which combined to constitute a single complex in their natural form. N-terminal sequencing indicated that both these protein fragments were encoded by the HP1118 gene. The purified protein exhibited γ-glutamyl transpeptidase activity, the inhibition of which by 6-diazo-5-oxo-L-norleucine resulted in a complete loss of apoptosis-inducing activity. To the best of our knowledge, the apoptosis-inducing function is a newly identified physiological role for bacterial γ-glutamyl transpeptidase. The apoptosis-inducing activity of the isogenic mutant γ-glutamyl transpeptidase-deficient strain was significantly lower compared with that of the parent strain, demonstrating that γ-glutamyl transpeptidase plays a significant role in H. pylori-mediated apoptosis. Our findings provide new insights into H. pylori pathogenicity and reveal a novel aspect of the bacterial γ-glutamyl transpeptidase function.

Original languageEnglish
Pages (from-to)443-451
Number of pages9
JournalMolecular Microbiology
Volume47
Issue number2
DOIs
Publication statusPublished - 2003

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

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    Shibayama, K., Kamachi, K., Nagata, N., Yagi, T., Nada, T., Doi, Y., Shibata, N., Yokoyama, K., Yamane, K., Kato, H., Iinuma, Y., & Arakawa, Y. (2003). A novel apoptosis-inducing protein from Helicobacter pylori. Molecular Microbiology, 47(2), 443-451. https://doi.org/10.1046/j.1365-2958.2003.03305.x