title: CagA-mediated pathogenesis of Helicobacter pylori.
abstract: Helicobacter pylori has been described as the main etiologic agent of gastric cancer, causing a considerable rate of mortality and morbidity in human population across the world. Although the infection mainly begins asymptomatically, but simply develops to peptic ulcer, chronic gastritis, lymphoma of the gastric mucosa and eventually adenocarcinoma. The major pathological feature of H. pylori infection is due to the activity of the cytotoxin-associated gene A (CagA), a 125-140 kDa protein encoded by the cag pathogenicity island (cagPAI). CagA is also known as the first bacterial onco-protein, ranking the H. pylori-mediated adenocarcinoma as the second most deadly cancer type worldwide. Upon cytoplasmic translocation CagA undergoes interacting with numerous proteins in phosphorylation dependent and independent manners within the gastric epithelial cells. The profound effect of CagA on multiple intracellular pathways causes major consequences such as perturbation of intracellular actin trafficking, stimulation of inflammatory responses and disruption of cellular tight junctions. Such activities of CagA further participate in development of the hummingbird phenotype and gastric cancer. This review is sought to provide a structural and functional analysis of the CagA protein with focus on demonstrating the molecular basis of the mechanism of CagA intracellular translocation and its interaction with intracellular targets.
authors.affiliation: Department of Biophysics, Institute of Fundamental Biology and Biotechnology, Siberian Federal University, Krasnoyarsk, Russian Federation; Institute of Molecular Medicine and Pathobiochemistry Research. Krasnoyarsk State Medical University. Krasnoyarsk, Russian Federation. Electronic address: a.tohidpour@gmail.com.
authors.forename: Abolghasem
authors.initials: A
authors.lastname: Tohidpour
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D013274:Stomach Neoplasms / Q000382:microbiology; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori
keywords: Adenocarcinoma; Crystal structure; EPIYA; Integrin α5β1; Phosphatidylserine; T4SS; cagPAI