Table 1.
Known ubiquitination-mediated inflammasome activation.
| Modification Type | Target | Enzyme | Function (Ref) |
|---|---|---|---|
| Deubiquitination | NLRP3 | NA | Deubiquitination of NLRP3 is required for its activation [98] |
| Deubiquitination | NLRP3 | BRCC3 | Deubiquitination of NLRP3 by BRCC3 promotes inflammasome activation [99] |
| Ubiquitination (K48) | NLRP3 | MARCH7 | MARCH7 mediates K48-linked polyubiquitination of NLRP3 and proteasome degradation [106] |
| Ubiquitination (K48/K63) | NLRP3 | ARIH2 | ARIH2 mediates K48- and K63-linked polyubiquitination of NLRP3 and negatively regulates NLRP3 inflammasome activation [108] |
| Ubiquitination | NLRP3 | TRAF6 | The ubiquitin E3 ligase activity of TRAF6 mediates NLRP3 oligomerization and inflammasome activation [112] |
| Ubiquitination (K63) | NLRP3 | Pellino2 | Pellino2 mediates K63-linked ubiquitination and activation of NLRP3 [110] |
| Ubiquitination (K48) | NLRP3 | TRIM31 | TRIM31 mediates K48-linked polyubiquitination of NLRP3 and inhibits NLRP3 inflammasome activation [107] |
| Ubiquitination | NLRP3 | Cullin1 | Cullin1 mediates NLRP3 ubiquitination and inhibits NLRP3 inflammasome activation [109] |
| Ubiquitination (K63) | NLRP3 | YopM | Bacterial E3 ligase YopM mediates K63-linked polyubiquitination of NLRP3 and induces NLRP3-mediated cell death [119] |
| Deubiquitination | NLRP3 | NleA | Bacterial effector NleA binds to NLRP3 and inhibits deubiquitination and activation of NLRP3 [120] |
| Ubiquitination | NLRP3 (Lys689) | FBXL2 | FBXL2 mediates ubiquitination and degradation of NLRP3 [113] |
| Ubiquitination | NLRP3 | NA | PKA induces phosphorylation of NLRP3 which results in NLRP3 ubiquitination and degradation [114] |
| Ubiquitination | GLMN-NLRP3/NLRC4 | IpaH7.8 | Bacterial E3 ligase IpaH7.8 mediates ubiquitination of GLMN, an inhibitor for the NLRP3 and NLRC4 inflammasomes, and induces inflammasome activation [118] |
| Linear ubiquitination | ASC | LUBAC | Linear ubiquitination of ASC is required for NLRP3/ASC assembly and activation [104] |
| Ubiquitination | ASC | NA | Autophagy induced by inflammasome signals targets polyubiquitinized ASC for degradation [97] |
| Deubiquitination | ASC | NA | Deubiquitination inhibition blocks ASC oligomerization and inflammasome activation [100] |
| Deubiquitination | ASC and NLRP3 | USP7 and USP47 | USP7 and USP47 mediate deubiquitination of ASC and NLRP3, which promotes ASC oligomerization and NLRP3 inflammasome activation [101] |
| Deubiquitination (K63) | ASC | USP50 | USP50 binds to ASC and directly deubiquitinates K63-linked polyubiquitination of ASC, which is required for ASC oligomerization and inflammasome activation [102] |
| Ubiquitination (K63) | ASC (Lys174) | TRAF3 | MAVS recruits TRAF3 to mediate K63-linked ubiquitination of ASC and promotes inflammasome activation [111] |
| Ubiquitination and N-terminal degradation | NLRP1B | NA or IpaH7.8 | Anthrax lethal toxin cleavage results in proteasome-mediated degradation of the N-terminal domains of NLRP1B and NLRP1B activation; Bacterial ubiquitin ligase IpaH7.8 degrades and activates NLRP1B [115] |
| Ubiquitination and N-terminal degradation | NLRP1B | UBR2/4 | UBR2/4 mediates ubiquitination of N-terminal domains of NLRP1B and proteasome degradation, which results in NLRP1B activation [116] |
| Ubiquitination and N-terminal degradation | NLRP1B | UBR2 and E2O | E3 ligase UBR2 and E2 conjugating enzyme E2O mediate ubiquitination and degradation of N-terminal domains of NLRP1B and NLRP1B activation [117] |
| Ubiquitin (p62 recruitment) | AIM2 | TRIM 11 | TRIM11 undergoes autoubiquitination and recruits AIM2 to p62 for degradation, which inhibits AIM2 inflammasome activation [121] |
| Ubiquitination | NLRC4(H443P) | SUG1-NA | SUG1 interacts with NLRC4 mutant NLRC4(H443P) and causes Caspase-8 activation and cell death [124] |
| Ubiquitination (K63) | Caspase-1 | cIAP1, cIAP2, TRAF2 | cIAP1, cIAP2, and TRAF2 mediate K63-linked polyubiquitination and activation of Caspase-1 [127] |
| Ubiquitination (K48) | IL-1β | BUBE2L3 | Caspas-1 target UBE2L3 mediates K48-linked polyubiquitination of pro-IL-1β and degradation [125] |
| Deubiquitination (K63) | IL-1β (Lys133) | A20 | A20 deubiquitinates IL-1β and suppresses spontaneous NLRP3 inflammasome activation [126] |