Table 1.

Intracellular modulators that suppress the activity of cGAS, cGAMP, and STING.

Target	Modulators	Modification	Mechanisms	Refs.
cGAS	AKT	Phosphorylation	Phosphorylates the active domain of cGAS	[56]
	BTK		Reduces the binding efficiency of DNA	[57]
	Caspase-1	Cleavage (degradation)	Dampens the production of type-I IFN	[51]
	TRIM38	Sumoylation	Inhibits the activation of cGAS without microbial invasion	[58]
	TTLL6	Polyglutamylation	Impedes the cGAS–DNA synthesis activity	[59]
	TTLL4	Monoglutamylation	Reduces the enzymatic activity of cGAS	[59]
	Cia-cGAS	Direct binding	Prevents the binding of cGAS to DNA	[60]
	OASL	Direct binding	Decreases the synthase activity of cGAS	[61]
cGAMP	ENP11	Phosphodiesterase	Hydrolyzes cGAMP	[62]
STING	USP13	Deubiquitylation	Prevents the recruitment of TBK1 by STING	[63]
	NLRC3	Direct binding	Impairs the interaction between STING and TBK1	[64]
	NLRX1	Direct binding	Impairs the interaction between STING and TBK1	[65]
	ULK1	Phosphorylation	Thwarts sustained type I IFN production by STING	[66]
	RNF5	Ubiquitylation	Degrades STING at mitochondria	[67]
	AP-1	Directly binding	Terminates the sorting of STING in Golgi	[68]
	2-BP	Directly binding	Suppresses palmitoylation of STING in Golgi	[69]

Abbreviations: AKT, RACα serine/threonine-protein kinase (also known as PKB); BTK, Bruton’s tyrosine kinase; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase family member 1; TRIM38, tripartite motif 38; TTLL6, tubulin-tyrosine ligase-like member 6; TTLL4, tubulin-tyrosine ligase-like member 4; USP13, ubiquitin specific peptidase 13; cia-cGAS, circular RNA with higher cGAS affinity than dsDNA; OASL, 20–50 oligoadenylate synthase; NLRC3, NOD-like receptor family 3 containing CARD domain; NLRX1, NLR family member X1; ULK1, serine/threonine UNC-51-like kinase (ULK1/ATG1); RNF5, RING finger domain; AP-1, adaptor protein complex 1; 2-BP, 2-bromopalmitate; cGAS, cyclic GMP-AMP synthase; cGAMP, cGMP-AMP; STING, stimulator of interferon genes.