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Granzyme-A Pathway

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CTLs (Cytotoxic T Lymphocytes) and NK (Natural Killer) cells are the key immune effectors that eradicate infected cells or tumors. To destroy these targets, CTLs and NK cells mostly use the granule exocytosis pathway, which releases perforin and Granzymes from cytolytic granules into the immunological synapse formed with the target. Granzyme-A and Granzyme-B, the most abundant Granzymes, are delivered to the target cell cytosol through perforin and independently induce cell death. The tryptase Granzyme-A activates cell death through a caspase-independent mechanism. Granzyme-A causes characteristic features of apoptosis, including membrane blebbing, loss of mitochondrial transmembrane potential, nuclear fragmentation and chromatin condensation; however, instead of the usual apoptotic double-stranded oligonucleosomal DNA fragmentation, Granzyme-A causes a distinctive form of DNA damage that is [...]


1.Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A.
Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J.
Nat Immunol. 2003 Feb;4(2):145-53.
2.Granzyme A activates another way to die.
Lieberman J.
Immunol Rev. 2010 May;235(1):93-104. doi: 10.1111/j.0105-2896.2010.00902.x. Review.
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