Table 1.
The regulation of ubiquitination, SUMOylation and expression of key molecules in the cGAS-STING pathway.
| Functions | Factors | Target | Proposed Mechanism | Reference |
|---|---|---|---|---|
| Factors promoting cGAS-STING pathway | ||||
| De-SUMOylation | SENP7 | cGAS | Cleaving SUMO on the K335/372/382 | (Cui et al., 2017) |
| SUMOylation | TRIM38 | cGAS STING |
Sumoylating to prevent their polyubiquitination and degradation | (Hu et al., 2016) |
| E3 ubiquitination | ||||
| RNF26 | STING | Catalyzing K11-linked polyubiquitination at K150 | (Qin et al., 2014) | |
| RNF115 | STING | Catalyzing the K63-linked polyubiquitination | (Zhang et al., 2020) | |
| RNF128 | TBK1 | Catalyzing the K63-linked polyubiquitination | (Song et al., 2016) | |
| RNF185 | cGAS | Catalyzing the K27-linked polyubiquitination | (Wang et al., 2017) | |
| TRIM41 | TBK1 NF-κB BCL10 |
Catalyzing the K63-linked polyubiquitylation of BCL10 to facilitate the activation of TBK1 and NF-κB | (Yu et al., 2021) | |
| TRIM32 | STING | Catalyzing K63-linked polyubiquitination at K20/150/224/236 | (Zhang et al., 2012) | |
| TRIM56 | cGAS | Catalyzing the monoubiquitination at K335 | (Seo et al., 2018) | |
| TRAF6 | cGAS | Promoting the activation of cGAS by ubiquitinating | (Chen and Chen, 2019) | |
| TRIM56 | STING | Catalyzing K63-linked polyubiquitination at K150 | (Tsuchida et al., 2010) | |
| AMFR INSIG1 |
STING | Catalyzing the K27-linked polyubiquitination | (Wang et al., 2014) | |
| MUL1 | STING | Catalyzing the ubiquitination of STING at K224 | (Ni et al., 2017) | |
| Ubc5 | IRF3 | Catalyzing the K63-linked polyubiquitination | (Zeng et al., 2009) | |
| Deubiquitination | ||||
| IFN-I | cGAS | TRIM14 induced by IFN-I to recruits USP14 to cleave the K48-linked polyubiquitination chain |
(Chen et al., 2016) | |
| EIF3S5 | STING | Cleaving the K48-linked polyubiquitination chain | (Luo et al., 2016) | |
| OTUD5 | STING | Cleaving the K48-linked polyubiquitination chain | (Guo et al., 2021) | |
| USP18 | STING | Recruiting USP20 to Remove K48-Linked ubiquitination |
(Zhang et al., 2016) | |
| USP20 | STING | Removing K48-linked ubiquitination | (Zhang et al., 2019) | |
| USP21 | STING | Cleaving K27/63-linked polyubiquitin chain | (Chen et al., 2017) | |
| USP27X | cGAS | Cleaving the K48-linked polyubiquitination chain | (Guo et al., 2019) | |
| USP29 | cGAS | Removing the K48-linked polyubiquitin chains | (Zhang et al., 2020) | |
| PSMD14 | IRF3 | Cleaving the K27-linked polyubiquitination at K313 to prevent IRF3 from autophagic degradation | (Wu et al., 2021) | |
| CYLD | STING | Removing the K48-linked polyubiquitin chains | (Zhang et al., 2018) | |
| Factors inhibiting cGAS-STING pathway | ||||
| De-SUMOylation | ||||
| SENP2 | cGAS STING |
Desumoylating to allow K48-linked ubiquitination | (Hu et al., 2016) | |
| SENP2 | IRF3 | Desumoylating to allow K48-linked ubiquitination | (Ran et al., 2011) | |
| E3 ubiquitination | ||||
| RNF178 | cGAS | Catalyzing the K63-linked ubiquitination at K411 | (Yang et al., 2022) | |
| RNF90 | STING | Catalyzing the K48-linked ubiquitination | (Yang et al., 2020) | |
| RNF5 | STING | Catalyzing the K48-linked ubiquitination at K150 | (Zhong et al., 2009) | |
| TRIM29 | STING | Catalyzing the K48-linked ubiquitination | (Xing et al., 2017) | |
| ASB8 | TBK1 | Catalyzing the K48-linked ubiquitination | (Guo et al., 2020) | |
| TRIP | TBK1 | Catalyzing the K48-linked ubiquitination | (Zhang et al., 2012) | |
| SOCS3 | TBK1 | Catalyzing the K48-linked ubiquitination | (Liu et al., 2015) | |
| THOC7 | TBK1 | Catalyzing the K48-linked ubiquitination | (He et al., 2019) | |
| c-Cbl | IRF3 | Catalyzing the K48-linked ubiquitination | (Zhao et al., 2016) | |
| TRIM26 | IRF3 | Catalyzing the K48-linked ubiquitination | (Wang et al., 2015) | |
| RBCK1 | IRF3 | Catalyzing the K48-linked ubiquitination | (Zhang et al., 2008) | |
| FoxO1 | IRF3 | Catalyzing the K48-linked ubiquitination | (Lei et al., 2013) | |
| TRIM21 | IRF3 | Catalyzing the K48-linked ubiquitination | (Higgs et al., 2008) | |
| Pin1 | IRF3 | Catalyzing the K48-linked ubiquitination | (Saitoh et al., 2006) | |
| RAUL | IRF3 IRF7 |
Catalyzing the K48-linked ubiquitination | (Yu and Hayward, 2010) | |
| TRIM30α | STING | Catalyzing the K48-linked ubiquitination | (Wang et al., 2015) | |
| Deubiquitination | ||||
| USP13 | STING | Cleaving the K27-linked polyubiquitination chain | (Sun et al., 2017) | |
| USP35 | STING | Cleaving the K6-, K11-, K27-, K29- or K63-linked polyubiquitination chain | (Zhang et al., 2021) | |
| USP49 | STING | Cleaving the K63-linked polyubiquitination chain | (Ye et al., 2019) | |
| MYSM1 | STING | Cleaving the K63-linked polyubiquitination chain | (Tian et al., 2020) | |
| OTULIN | NF-κB IFN-I |
Suppressing the linear ubiquitination on the immunoproteasome subunit; NF-κB signaling↓ IFN-I signaling↓ |
(Tao et al., 2021) | |
| HER2 | TBK1 | Phosphorylating TBK1 at Ser511 to disrupt the TBK1-STING interaction and K63-linked ubiquitination of TBK1 | (Wu et al., 2019) | |