Fig. 2: Post-translational modifications (PTMs) regulate NLRP3 inflammasome activation.
From: Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors
Schematic structure and PTM sites on different domains of NLRP3 (LRR, NACHT, and PYD). BRCC3 and PTPN22 target the LRR domain of NLRP3 to promote NLRP3 inflammasome activation by deubiquitination and dephosphorylation, respectively. MARCH7 and FBXL2 ubiquitinate NLRP3 LRR domain to inhibit NLRP3 inflammasome activation. Phosphorylation of NLRP3 at S194 and S293 by JNK1 and PKD, respectively, are key events for NLRP3 inflammasome activation. PKA and ARIH2 can phosphorylate and ubiquitinate NLRP3 NACHT domain, respectively, to abrogate NLRP3 inflammasome activation. TRIM31 directly interacts with PYD domain of NLRP3 and promotes its K48-linked ubiquitination, leading to NLRP3 proteasomal degradation and inhibition. Dephosphorylation of NLRP3 PYD domain at S5 by PP2A promotes NLRP3–ASC as well as NLRP3 PYD–PYD interactions
