Stability of Helicobacter pylori CagA oncoprotein in human gastric epithelial cells.
Upon delivery into gastric epithelial cells, Helicobacter pylori cytotoxin-associated gene A (CagA) binds and deregulates cellular proteins such as Src homology 2 domain-containing protein tyrosine phosphatase 2 and partitioning-defective 1 (PAR1), thereby acting as an epigenetic oncoprotein that promotes early phases of gastric cancer development. To elucidate the spatial and temporal contribution of CagA to carcinogenesis, it is crucial to know the stability of CagA in host cells. Here we show that the biological half-life of CagA is about 200 min in gastric epithelial cells. Furthermore, deletion of the PAR1-binding sequence accelerates CagA degradation. Thus, CagA is a relatively short half-life protein whose stability may be modulated through complex formation with PAR1.
Ishikawa
Susumu
S
Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
Ohta
Tomomi
T
Hatakeyama
Masanori
M
D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D017346:Protein Serine-Threonine Kinases