The Many Ways to Deal with STING
Abstract
:1. Introduction
2. cGAS-STING Canonical Signaling Pathway
3. STING Non-Canonical Signaling Pathway
4. STING Regulation and Inhibition Mechanisms
Modification | Protein Involved | Locus (Human STING) | Outcome | |
---|---|---|---|---|
Positive regulation | K63-linked ubiquitination | TRIM32 [91,92], TRIM56 [92], UBXN3B [107], MUL1 [43], RNF115 [98] | K20, K150, K224, K236, K289 | Increase of STING-TBK1 interaction |
K27-linked ubiquitination | AMFR [108] | K137, K150, K224, K236 | Increase of STING-TBK1 interaction | |
K11-linked ubiquitination | RNF26 [97] | K150 | Prevention of K48-linked ubiquitination | |
K48-linked deubiquitination | USP20 [99,100,102], USP44 [101], CYLD [109], EIF3S5 [42] and OTUD5 [110] | K33, K236, K150, K347 | Increase of STING stability | |
Y245 phosphorylation | EGFR [40] | Y245 | Enabling STING trafficking | |
S358 phosphorylation | TBK1 [48] | S358 | Enabling TBK1-STING complex formation | |
S366 phosphorylation | TBK1 [46] | S366 | Enabling STING interaction with IRF3 | |
Palmitoylation | DHHC3, DHHC7, DHHC15 [45] | C88, C91 | Induction of STING oligomerization | |
SUMOylation | TRIM38 [90] | K338 | Prevention of STING degradation | |
Negative regulation | K48-linked ubiquitination | TRIM29 [93], TIM30α [94], RNF5 [95], RNF90 [96] | K370, K275, K150 | Induction of STING degradation |
K63-linked deubiquitination | USP49 [103], USP21 [105], USP35 [106], MYSM1 [111] | K150 | Decrease of STING interaction with TBK1 | |
K27- linked deubiquitination | USP13 [104], USP21 [105], USP35 [106] | Unknown | Decrease of STING interaction with TBK1 | |
K6-, K11- and K29-linked deubiquitination | USP35 [106] | Unknown | Decrease of STING interaction with TBK1 | |
S366 phosphorylation | ULK1 [88] | S366 | Inhibition of STING-dependent IRF3 activation | |
S358 dephosphorylation | PPM1A [48] | S358 | Reduction of STING oligomerization | |
deSUMOylation | SENP2 [90] | K338 | Induction of STING degradation |
5. Tridimensional Structure of STING and Conformational Changes upon Activation
6. STING Polymorphisms
6.1. Gain-of-Function Mutations of STING
6.2. Loss-of-Function Mutations of STING
7. Structural Insight into Ligand-STING Interaction
7.1. Cyclic Di-Nucleotides as Natural STING Activators
7.2. Small Organic Molecules as Drug Candidates
8. Perspectives
Supplementary Materials
Funding
Conflicts of Interest
References
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2′3′-cGAMP | 3′3′-cGAMP | ||
cdiGMP | cdiAMP | ||
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Coderch, C.; Arranz-Herrero, J.; Nistal-Villan, E.; de Pascual-Teresa, B.; Rius-Rocabert, S. The Many Ways to Deal with STING. Int. J. Mol. Sci. 2023, 24, 9032. https://doi.org/10.3390/ijms24109032
Coderch C, Arranz-Herrero J, Nistal-Villan E, de Pascual-Teresa B, Rius-Rocabert S. The Many Ways to Deal with STING. International Journal of Molecular Sciences. 2023; 24(10):9032. https://doi.org/10.3390/ijms24109032
Chicago/Turabian StyleCoderch, Claire, Javier Arranz-Herrero, Estanislao Nistal-Villan, Beatriz de Pascual-Teresa, and Sergio Rius-Rocabert. 2023. "The Many Ways to Deal with STING" International Journal of Molecular Sciences 24, no. 10: 9032. https://doi.org/10.3390/ijms24109032