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A novel apoptosis‐inducing protein from Helicobacter pylori
Author(s) -
Shibayama Keigo,
Kamachi Kazunari,
Nagata Noriyo,
Yagi Tetsuya,
Nada Toshi,
Doi Yohei,
Shibata Naohiro,
Yokoyama Keiko,
Yamane Kunikazu,
Kato Haru,
Iinuma Yoshitsugu,
Arakawa Yoshichika
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03305.x
Subject(s) - biology , apoptosis , helicobacter pylori , microbiology and biotechnology , mutant , gene , biochemistry , genetics
Summary Helicobacter pyloriinfection induces apoptosis in gastric epithelial cells. Here, we report a novel apoptosis‐inducing protein that functions as a leading factor inH. pylori‐mediated apoptosis induction. We purified the protein fromH. pyloriby 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 inH. pylori‐mediated apoptosis. Our findings provide new insights intoH. pylori pathogenicity and reveal a novel aspect of the bacterial γ‐glutamyl transpeptidase function.