Inducing Pyroptosis via Gasdermin B and Gasdermin E Cleavage

Gasdermin B (GSDMB) and gasdermin E (GSDME) are two members of the gasdermin family, which shares a conservative gasdermin-N domain capable of executing pyroptotic cell death, through perforating the plasma membrane from inside of the cell. Both GSDMB and GSDME are autoinhibited in the resting stage and require proteolytic cleavage to unleash the pore-forming activity that otherwise is masked by their C-terminal gasdermin-C domain. GSDMB is cleaved and activated by granzyme A (GZMA) from cytotoxic T lymphocytes or natural killer cells, while GSDME is activated by caspase-3 cleavage downstream of various well-known "apoptotic" stimuli. Here, we describe the methods for inducing pyroptosis through GSDMB and GSDME cleavage.