Granzyme

Granzymes are serine proteases that are released by cytoplasmic granules within cytotoxic T cells and natural killer cells. Their purpose is to induce apoptosis within virus-infected cells, thus destroying them.cite journal |author=Bots M, Medema JP |title=Granzymes at a glance |journal=J. Cell. Sci. |volume=119 |issue=Pt 24 |pages=5011–4 |year=2006 |doi= 10.1242/jcs.03239 |pmid=17158907]

Cytotoxic T cells and natural killer cells release a protein called perforin, which attacks the target cells. Researchers used to think that perforin creates pores within the cells, through which the granzymes can enter, inducing apoptosis. However, new evidence indicates that GrB complex (GrB, perforin, and another protein (glycopectin?)) can enter a cell through the mannose 6-phosphate receptor (or another receptor found in tumor cells) and is enclosed in a vesicle (a sac).cite journal |author=Buzza MS, Bird PI |title=Extracellular granzymes: current perspectives |journal=Biol. Chem. |volume=387 |issue=7 |pages=827–37 |year=2006 |pmid=16913832 |doi=10.1515/BC.2006.106] Perforin then allows GrB to pass through the vesicle surface and into the cell, causing apoptosis by various pathways.

They do so by cleaving caspases (especially caspase-3), which in turn activates caspase-activated DNase. This enzyme degrades DNA, thus inducing apoptotic cascades. Also, GrB cleaves the protein Bid, which recruits the protein Bax and Bak to change the membrane permeability of the mitochondria, causing the release of cytochrome c (which is one of the parts needed to form caspase-9), Smac/Diablo and Omi/HtrA2 (which suppress the inhibitor of apoptosis proteins(IAPs)), among other proteins. As well, GrB is shown to cleave many of the chemicals responsible for apoptosis without the aid of caspase, as proven by experiments on caspase knockout mice CTL cells incubated with other cells.

Granzyme secretion can be detected and measured using Western Blot or ELISA techniques. Granzyme secreting cells can be identified and quantified by flow cytometry or ELISPOT.

Genes

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References