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. Author manuscript; available in PMC: 2016 May 1.
Published in final edited form as: Virology. 2015 Mar 7;0:52–65. doi: 10.1016/j.virol.2015.02.033

Figure 4. Regulation of the cGAS-STING pathway by ubiquitination.

Figure 4

cGAS recognizes viral DNA in the cytoplasm and synthesizes cyclic GMP-AMP (cGAMP). cGAMP then activates STING on the ER, inducing downstream signaling for type-I IFN induction. STING is regulated by three types of polyubiquitination: K11-linked and K63-linked ubiquitination of K150 by RNF26 and TRIM56 or TRIM32, respectively, facilitating STING activation and type-I IFN gene expression. Besides K500, TRIM32 ubiquitinates three other residues in STING (K20, K224 and K236). Furthermore, K500 in STING is covalently modified by K48-linked ubiquitination mediated by RNF5. RNF5-induced STING ubiquitination leads to STING degradation.