title: A novel apoptosis-inducing protein from Helicobacter pylori.
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 gamma-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 gamma-glutamyl transpeptidase. The apoptosis-inducing activity of the isogenic mutant gamma-glutamyl transpeptidase-deficient strain was significantly lower compared with that of the parent strain, demonstrating that gamma-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 gamma-glutamyl transpeptidase function.
authors.affiliation: Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo 208-0011, Japan. keigo@nih.go.jp
authors.forename: Keigo
authors.initials: K
authors.lastname: Shibayama
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kamachi
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yagi
authors.forename: Toshi
authors.initials: T
authors.lastname: Nada
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Shibata
authors.forename: Keiko
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Yamane
authors.forename: Haru
authors.initials: H
authors.lastname: Kato
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Iinuma
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Arakawa
mesh_terms: D017209:Apoptosis; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D014407:Tumor Cells, Cultured; D014774:Virulence; D005723:gamma-Glutamyltransferase / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D005723:gamma-Glutamyltransferase