The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor
Helicobacter pylori is a microaerophilic, spiral-shaped and gram-negative microorganism that produces various virulence factors such as CagA, VacA, urease, and host cells adhesins, which in a synchronous concert, allow H. pylori to colonize and infect the host gastric epithelium. H. pylori infection...
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| Format: | Article |
| Language: | English |
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Siberian Federal University
2017-04-01
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| Series: | Журнал Сибирского федерального университета: Серия Биология |
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| Online Access: | http://elib.sfu-kras.ru/bitstream/2311/32143/7/01_Iunusova.pdf |
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| author | Alfiia I. Iunusova Irina S. Litvinova Polina A. Karpenok Abolghasem Tohidpour |
| author_facet | Alfiia I. Iunusova Irina S. Litvinova Polina A. Karpenok Abolghasem Tohidpour |
| author_sort | Alfiia I. Iunusova |
| collection | DOAJ |
| description | Helicobacter pylori is a microaerophilic, spiral-shaped and gram-negative microorganism that produces various virulence factors such as CagA, VacA, urease, and host cells adhesins, which in a synchronous concert, allow H. pylori to colonize and infect the host gastric epithelium. H. pylori infection is associated with some severe side effects in human, such as gastritis, peptic ulcer, non-Hodgkin’s lymphoma and adenocarcinoma. CagA is the most notorious virulence factor of H. pylori. It is known as the first bacterial oncoprotein. The gene encoding CagA is localized on the cag pathogenicity island (cagPAI), a 40kbp DNA segment which also carries genes for the type four secretion system (T4SS) of H. pylori. The interaction of CagA with intracellular partner proteins leads to some irreversible alteration of host cells by increasing cell size, elevating motility, phenomena known as the “hummingbird phenotype”. CagA also disrupts the epithelium apical junctions and thereby destroys the normal epithelial architecture. A tyrosine phosphorylation site, named EPIYA motif, helps CagA to bind to cytosolic proteins in a phosphorylation-dependent manner. CagA is also interacts with host proteins in a phosphorylation-independent fashion, which altogether will assist to develop adenocarcinoma in infected cells. This review summarizes the core data on the structure and function of CagA and its role in conferring the main pathophysiologic effects of H. pylori infection as well as suggesting a therapeutic option for treatment of H. pylori infection based on CagA virulence |
| first_indexed | 2024-12-11T19:48:46Z |
| format | Article |
| id | doaj.art-c66a4dda70dc4872ab1304a818b72a13 |
| institution | Directory Open Access Journal |
| issn | 1997-1389 2313-5530 |
| language | English |
| last_indexed | 2024-12-11T19:48:46Z |
| publishDate | 2017-04-01 |
| publisher | Siberian Federal University |
| record_format | Article |
| series | Журнал Сибирского федерального университета: Серия Биология |
| spelling | doaj.art-c66a4dda70dc4872ab1304a818b72a132022-12-22T00:52:51ZengSiberian Federal UniversityЖурнал Сибирского федерального университета: Серия Биология1997-13892313-55302017-04-01111415http://elib.sfu-kras.ru/handle/2311/32143The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence FactorAlfiia I. Iunusova0Irina S. Litvinova1Polina A. Karpenok2Abolghasem Tohidpour3Siberian Federal University 79 Svobodny, Krasnoyarsk, 660041, RussiaSiberian Federal University 79 Svobodny, Krasnoyarsk, 660041, RussiaSiberian Federal University 79 Svobodny, Krasnoyarsk, 660041, RussiaSiberian Federal University 79 Svobodny, Krasnoyarsk, 660041, RussiaHelicobacter pylori is a microaerophilic, spiral-shaped and gram-negative microorganism that produces various virulence factors such as CagA, VacA, urease, and host cells adhesins, which in a synchronous concert, allow H. pylori to colonize and infect the host gastric epithelium. H. pylori infection is associated with some severe side effects in human, such as gastritis, peptic ulcer, non-Hodgkin’s lymphoma and adenocarcinoma. CagA is the most notorious virulence factor of H. pylori. It is known as the first bacterial oncoprotein. The gene encoding CagA is localized on the cag pathogenicity island (cagPAI), a 40kbp DNA segment which also carries genes for the type four secretion system (T4SS) of H. pylori. The interaction of CagA with intracellular partner proteins leads to some irreversible alteration of host cells by increasing cell size, elevating motility, phenomena known as the “hummingbird phenotype”. CagA also disrupts the epithelium apical junctions and thereby destroys the normal epithelial architecture. A tyrosine phosphorylation site, named EPIYA motif, helps CagA to bind to cytosolic proteins in a phosphorylation-dependent manner. CagA is also interacts with host proteins in a phosphorylation-independent fashion, which altogether will assist to develop adenocarcinoma in infected cells. This review summarizes the core data on the structure and function of CagA and its role in conferring the main pathophysiologic effects of H. pylori infection as well as suggesting a therapeutic option for treatment of H. pylori infection based on CagA virulencehttp://elib.sfu-kras.ru/bitstream/2311/32143/7/01_Iunusova.pdfadenocarcinomacagPAIEPIYAT4SShummingbird phenotypecagPAIEPIYAT4SS |
| spellingShingle | Alfiia I. Iunusova Irina S. Litvinova Polina A. Karpenok Abolghasem Tohidpour The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor Журнал Сибирского федерального университета: Серия Биология adenocarcinoma cagPAI EPIYA T4SS hummingbird phenotype cagPAI EPIYA T4SS |
| title | The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor |
| title_full | The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor |
| title_fullStr | The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor |
| title_full_unstemmed | The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor |
| title_short | The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor |
| title_sort | cytotoxin associated gene a caga of helicobacter pylori the paradigm of an oncogenic virulence factor |
| topic | adenocarcinoma cagPAI EPIYA T4SS hummingbird phenotype cagPAI EPIYA T4SS |
| url | http://elib.sfu-kras.ru/bitstream/2311/32143/7/01_Iunusova.pdf |
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