Table 1.
Post-translational modifications of proteins in cytosolic DNA sensing signaling pathways.
| Protein | Post-translational modification | Modifying enzyme | Modification site(s) | Function | Reference |
|---|---|---|---|---|---|
| cGAS | Phosphorylation | Akt | mS291/hS305 | Inhibits cGAS enzymatic activity | (40) |
| Phosphorylation | CDK1 | mS291/hS305 | Inhibits cGAS enzymatic activity | (41) | |
| Phosphorylation | BLK | hY215 | Facilitates cGAS cytosolic retention | (42) | |
| Phosphorylation | DNA-PK | hT68/hS213 | Inhibits cGAS enzymatic activity | (43) | |
| Phosphorylation | Aurora kinase B | hS13/S37/S64/T69/T91/S116/S129/S143 | inhibits cGAS activity during mitosis | (44) | |
| Dephosphorylation | PPI | mS291/hS305 | Restores cGAS activity in the cytoplasm upon mitotic exit | (41) | |
| Dephosphorylation | PPP6C | mS420/hS435 | Prevents cGAS from binding to GTP and inhibits cGAS activity | (45) | |
| Mono-ubiquitination | TRIM56 | mK335 | Promotes cGAS dimerization and DNA-binding | (46) | |
| Polyubiquitination | RNF185 | mK173/mK384 (K27-linked) | cGAS activation | (47) | |
| Deubiquitination | USP14 | hK414 (K48-linked) | cGAS stabilization | (48) | |
| Deubiquitination | USP27X | (K48-linked) | cGAS stabilization | (49) | |
| Deubiquitination | USP29 | hK271 (K48-linked) | cGAS stabilization | (50) | |
| SUMOylation | TRIM38 | mK217/mK464/hk231/hK497 | cGAS stabilization | (51) | |
| DeSUMOylation | SENP2 | mK217/mK464 | cGAS stabilization | (51) | |
| DeSUMOylation | SENP7 | mK335/mK372/mK382 | cGAS activation by enhancing cGAS dimerization and DNA-binding | (52) | |
| Poly-neddylation | RNF111 | hK231/hK421 | cGAS dimerization and activation | (53) | |
| De-neddylation | SENP8 | hK231/hK421 | cGAS inhibition | (53) | |
| Methylation | PRMT5 | hR124 | cGAS inhibition by blocking DNA binding | (54) | |
| Acetylation | KAT5 | hK47/hK56/hL62/hK83 | facilitates DNA binding and cGAS activation | (55) | |
| Deacetylation | HDAC3 | hK384/hK394/hK414 | facilitates DNA binding and cGAS activation | (56) | |
| Poly-glutamylation | TTLL6 | mE272/hE286 | cGAS inhibition by blocking DNA binding | (57) | |
| Mono-glutamylation | TTLL4 | mE302/hE314 | cGAS inhibition | (57) | |
| Deglutamylation | CCP5 | mE302 | cGAS activation | (57) | |
| Deglutamylation | CCP6 | mE272 | cGAS activation | (57) | |
| IFI16 | Phosphorylation | pUL97 | IFI16 relocalization to cytoplasm | (58) | |
| Poly-ubiquitination | TRIM21 | hK3/K4/K6 (K48-linked) | IFI16 degradation | (59) | |
| Ubiquitination | ICP0 | IFI16 degradation | (60) | ||
| Acetylation | p300 | within NLS | IFI16 cytoplasmic retention | (61) | |
| AIM2 | Deubiquitination | USP21 | AIM2 stabilization | (62) | |
| Degradation by selective autophagy | TRIM11 | AIM2 degradation via p62-dependent selective autophagy | (63) | ||
| DHX9 | Phosphorylation | PI3KKs | S279/S321 | Chemoresistance | (64) |
| Ubiquitination | SPOP | (K48-linked) | DHX9 degradation | (65) | |
| Ubiquitination | RNF168 | (K63-linked) | DHX9 recruitment to R-loop-prone genomic loci | (66) | |
| DDX41 | Phosphorylation | BTK kinase | hY414 | DDX41 activation | (67) |
| Ubiquitination | TRIM21 | hK9/hK115 | DDX41 degradation | (68) | |
| DDX60 | Phosphorylation | EGFR | hY793/hY796 | Type 1 INF production | (69) |
| MRE11 | Phosphorylation | CK2, PLK1 | hS649/hS688 | MRN complex assembly to initiate DNA repair | (70) |
| Phosphorylation | ATM | hS646/hS678 | The MRC complex disruption upon DNA damage | (71) | |
| Phosphorylation | PLK1 | hS688 | MMAP-MRN complex formation | (72, 73) | |
| Phosphorylation | RSK | hS676 | Disrupts MRE11 binding to DNA | (74) | |
| Phosphorylation | P70-S6K | MRN complex disruption | (75) | ||
| Ubiquitination | UBQLN4 | MRE11 degradation | (76) | ||
| Ubiquitination | clAP2 | MRE11 degradation | (77) | ||
| UFMylation | hK282 | MRN complex recruitment to damaged DNA | (78) | ||
| UFMylation | hK281/hK282 | Maintaining telomere length and aiding cell survival | (79) | ||
| Methylation | PRMT1 | haa566-600 | Intra-S-phase DNA damage checkpoint response | (80) | |
| STING | Phosphorylation | TBK1 | hS366/mS365 | STING activation | (81) |
| Phosphorylation | ULK1 | hS366/mS365 | STING degradation | (82) | |
| Phosphorylation | TBK1/ULK1/2 | mS365 | STING activation by facilitating recruitment of “Senp2” | (51) | |
| Ubiquitination | RNF5 | hK150 | STING degradation | (83) | |
| Ubiquitination | TRIM30a | hK275 | STING degradation | (84) | |
| Ubiquitination | TRIM29 | hK370 | STING degradation | (85) | |
| Ubiquitination | RNF26 | hK150 | STING stabilization | (86) | |
| Ubiquitination | TOLLIP | STING stabilization at resting states | (87) | ||
| Ubiquitination | RNF115 | hK20/K224/K289 | STING activation and TBK1 recruitment | (88) | |
| Ubiquitination | TRIM56 | hK150 | STING dimerization and activation | (89) | |
| Ubiquitination | AMFR | hK137/hK150/hK224/hK236 | STING activation and TBK1 recruitment | (90) | |
| Ubiquitination | TRIM32 | hK20/K224/K236 | STING activation and TBK1 recruitment | (91) | |
| Ubiquitination | MUL1 | hK224 | STING trafficking and activation | (92) | |
| Deubiquitination | USP20 | (K48-linked) | STING stabilization | (93) | |
| Deubiquitination | EIF3S5 | (K48-linked) | STING stabilization | (94) | |
| Deubiquitination | CYLD | STING stabilization | (95) | ||
| Deubiquitination | USP13 | haa301-863 (K63-linked) | Impairs STING binding to TBK1 | (96) | |
| Deubiquitination | MYSM1 | hK150 (K63-linked) | STING inhibition | (97) | |
| Deubiquitination | USP21 | STING inactivation | (98) | ||
| SUMOylation | TRIM38 | hK338 | STING stabilization and activation | (51) | |
| De-SUMOylation | SENP2 | STING degradation | (51) | ||
| palmitoylation | DHHC3/DHHC7/DHHC15 | hC88/C91 | STING trafficking and activation | (99) | |
| Oxidation | hC148/mC147 | STING inactivation | (100) |
The orange color indicates activation of the indicated molecule by indicated modifications; the blue color indicates suppression of the indicated molecules by indicated modifications.