Deubiquitinases: Novel Therapeutic Targets in Immune Surveillance?

Figure 3

Regulation of the NLRP3 inflammasome activation by the ubiquitin-proteasome system. Assembly of the NLRP3 inflammasome complex occurs in response to a wide variety of danger signals including ATP, bacterial toxins, or particulate matter such as monosodium urate crystals. The ubiquitin ligases MARCH7 and SCFBXL2 add K48-linked poly-Ub chains to NLRP3 as a mean to control its levels by proteasomal degradation. cIAPs on the contrary add K63 poly-Ub chains to NLRP3 and caspase-1, contributing to the assembly of the complex. A20 also acts as a negative regulator of this complex. However, BRCC3 can deubiquitinate NLRP3, allowing it to form the complex and acting as a positive regulator of this pathway. TRAF3, TRAF6, and LUBAC also ubiquitinate ASC by K63 or M1 poly-Ub chains and this contributes to complex assembly. How other DUBs contribute to the assembly of the NLRP3 complex still remains unknown.