Cytotoxicity-associated immunodominant antigen | |||||||
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Organism | |||||||
Symbol | CagA | ||||||
UniProt | P55980 | ||||||
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Cytotoxicity-associated immunodominant antigen (CagA), also CAG pathogenicity island protein 26, and cytotoxin-associated antigen A is a 120–145kDa protein encoded on the 40kb CAG pathogenicity island of Helicobacter pylori by the cagA gene.[1][2] CagA is a major virulence factor of H. pylori.
H. pylori strains can be divided into CagA positive or CagA negative. Approximately 30 – 40% of H. pylori strains isolated in Western countries are cag PAI positive, whereas most of the East Asian isolates are cag PAI positive. This difference is attributed to differences in amino acids present.[3]
The cag PAI also encodes for a type IV secretion system which is used to "inject" CagA into a target cell upon H. pylori attachment. After translocation, CagA localises to the inner surface of the cell membrane and undergoes tyrosine phosphorylation by Src family kinases (e.g. Fyn and Lyn).[1]
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Transcription
Role in cancer
H. pylori infection is associated with MALT lymphoma and gastric adenocarcinoma; CagA is an oncoprotein involved in the development of cancer.[4] Phosphorylated CagA is able to interact with the SHP-2 tyrosine phosphatase, rendering it functionally active, triggering a host cell morphological change to a more motile phenotype known as the "hummingbird phenotype".[1] This phenotype mimics an effect produced by hepatocyte growth factor which may participate in various aspects of cancer, including metastasis. [5] CagA is also a highly antigenic protein that is associated with a prominent inflammatory response by eliciting interleukin-8 production.[4]
The Cag PAI
References
- ^ a b c Hatakeyama M, Higashi H (December 2005). "Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis". Cancer Science. 96 (12): 835–843. doi:10.1111/j.1349-7006.2005.00130.x. PMID 16367902.
- ^ Sun Q, Yuan C, Zhou S, Lu J, Zeng M, Cai X, Song H (2023). "Helicobacter pylori infection: a dynamic process from diagnosis to treatment". Front Cell Infect Microbiol. 13: 1257817. doi:10.3389/fcimb.2023.1257817. PMC 10621068. PMID 37928189.
- ^ Hatakeyama M (2017). "Structure and function of Helicobacter pylori CagA, the first-identified bacterial protein involved in human cancer". Proc Jpn Acad Ser B Phys Biol Sci. 93 (4): 196–219. Bibcode:2017PJAB...93..196H. doi:10.2183/pjab.93.013. PMC 5489429. PMID 28413197.
- ^ a b Yamaoka Y (November 2010). "Mechanisms of disease: Helicobacter pylori virulence factors". Nature Reviews. Gastroenterology & Hepatology. 7 (11): 629–641. doi:10.1038/nrgastro.2010.154. PMC 3137895. PMID 20938460.
- ^ Lax AJ (April 2005). "Opinion: Bacterial toxins and cancer--a case to answer?". Nature Reviews. Microbiology. 3 (4): 343–349. doi:10.1038/nrmicro1130. PMID 15806096. S2CID 6129498.
External links
- "Search: "cytotoxin-associated gene A" "Helicobacter pylori"". Protein. NCBI.