Stability of Helicobacter pylori CagA oncoprotein in human gastric epithelial cells

FEBS Lett. 2009 Jul 21;583(14):2414-8. doi: 10.1016/j.febslet.2009.06.043. Epub 2009 Jun 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Epithelial Cells / metabolism*
  • Gastric Mucosa / cytology*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / metabolism*
  • Humans
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Stability
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Tumor Cells, Cultured

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • cagA protein, Helicobacter pylori
  • Protein Serine-Threonine Kinases