During apoptosis, activated caspase-3 (CASP3) and to a lesser degree CASP7 inactivate gasdermin D (GSDMD) by cleaving GSDMD at position D87 generating p20 (GSDMD(1-87)) and p43 (GSDMD(88-484)) fragments (Taabazuing CY et al. 2017). This cleavage site is evolutionarily conserved and lies within the N-terminal fragment (p30, GSDMD(1-275)) that forms membrane pores. Proteolysis at this site renders GSDMD incapable of activating pyroptosis (Taabazuing CY et al. 2017). This pathway does not seem to play a key role during animal development as wild-type and Gsdmd-deficient mice both develop normally.
Taabazuing, CY, Okondo, MC, Bachovchin, DA
cysteine-type endopeptidase activity of Caspase-3 [cytosol]
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