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. 2022 Dec 6;12(12):1825. doi: 10.3390/biom12121825

Figure 5.

Figure 5

Overview of DUBs-mediated regulation of pyroptosis. DAMPs, PAMPs, and other stimuli promote inflammasome formation, such as NLRP3-PYCARD-CASP1. NEK7-NLRP3 binding prevents NLRP3 inflammasome formation. CYLD deubiquitinates NEK7 and promotes NEK7-NLRP3 association to inhibit NLRP3 inflammasome formation. While BRCC3/ABRAXAS2 deubiquitinates NLRP3 to promote NLRP3 inflammasome formation, the DUBs UCHL5, WDR48/USP1, and STAMBP promote NLRP3 inflammasome formation. USP5 promotes NLRP3 degradation and attenuates NLRP3 inflammasome activation. CYLD-NLRP6 and USP21-AIM2 regulate the NLRP6-PYCARD and AIM2 inflammasome, respectively. When inflammasome formation is activated, the inflammasome produces mature CASP1, which cleaves intact GSDMD. N-terminal GSDMD (GSDMD-NT) translocates to the inner leaflet of the plasma membrane, causing membrane rupture and release of DAMPs such as IL1A, IL1B, IL18, and HMGB1.