FIGURE 1.

Mechanisms of NEK7-mediated NLRP3 inflammasome activation. NEK7 directly binds with NLRP3, which triggers canonical NLRP3 inflammasome activation, including the activation of caspase 1, cleavage of pro-IL-1β, and pro-IL-18, producing mature IL-1β and IL-18, which are secreted to the extracellular space as inflammatory effectors. Disordered cellular homeostasis, including K⁺ efflux, Ca²⁺ signaling, chloride efflux, and mitochondrial dysfunction (mtROS), are the upstream signals that regulate NEK7-mediated NLRP3 inflammasome activation by either upregulating NEK7 expression or inducing the binding of NEK7 to NLRP3. Post-translational modification of NEK7 regulated by centrosome proteins (spata, CYLD, and PLK4) and the deglutathionylating enzyme GSTO1-1 that inhibits or induces the binding of NEK7 to NLRP3, respectively, affect NLRP3 inflammasome activation.