3.4.21.78 gasdermin B + H2O granzyme A from cytotoxic lymphocytes cleaves gasdermin B (GSDMB) to trigger pyroptosis in target cells, predominantly at Lys244 within the interdomain linker. This cleavage unmaskes the pore-forming activity of GSDMB. Granzyme A, delivered into GSDMB-reconstituted cells by electroporation or perforin, induces extensive pyroptosis with interdomain cleavage of GSDMB 3.4.21.78 histone H4 + H2O histone H4 is a substrate for GzmA in staurosporine-induced cells 3.4.21.78 Ku70 double strand break repair protein + H2O - 3.4.21.78 additional information cell death-inducing serine protease 3.4.21.78 additional information most abundant protease in cytotoxic T lymphocytes, granzyme A pathway of cell-mediated cytotoxicity, produced as proenzyme, activated by the dipetidyl exopeptidase cathepsin C 3.4.21.78 additional information the enzyme may function as a common component necessary for lysis of target cells by cytotoxic T-lymphocytes and natural killer cells 3.4.21.78 additional information TSP-1 has the capacity to stimulate B lymphocytes for proliferation in the absence of antigen 3.4.21.78 additional information overview: possible roles of granzyme A: 1. involvement in T or NK cell-mediated cytolysis, 2. in extravasation of T-lymphocytes, 3. in regulation of B cell growth, 4. in control of viral infection 3.4.21.78 additional information by cleaving a variety of basement membrane-associated substrates, granzyme A may disintegrate the supramolecular structure of subendothelial basement membranes in a way that allows a more rapid emigration of activated T-cells 3.4.21.78 additional information extracellular enzyme is delivered to the cytosol by perforin, where it causes a rapid increase in reactive oxygen species and mitochondrial transmembrane potential loss, but does not cleave bid or cause apoptotic factor release. Mitochondrial effect is direct, does not require cytosol, and is insensitive to bcl-2 and caspase inhibition. Mitochondrial damage is an essential first step in killer cell granule-mediated pathways of apoptosis 3.4.21.78 additional information compared with granzyme B, granzyme A is minor effector of target cell lysis by natural killer cells 3.4.21.78 NADH dehydrogenase (ubiquinone) Fe-S protein 3 + H2O - 3.4.21.78 protein NDUFS3 + H2O GzmA cleavage of native Ndufs3 disrupts complex I electron transport