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

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)


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
Issue number2
Publication statusPublished - 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology


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