Skip to main content
. 2017 Aug 14;47(9):1414–1426. doi: 10.1002/eji.201746959

Figure 3.

Figure 3

Regulation of antiviral signaling pathways by ubiquitination. TLR9 and TLR3 are K48‐linked ubiquitinated by Triad3A and subsequently degraded by proteasome. RIG‐I is K48‐linked ubiquitinated by RNF122 and RNF125 and then undergoes proteolytic degradation. USP4 remove the K48‐linked ubiquitination of RIG‐I and promotes RIG‐I signaling. TRIM25, TRIM4, RNF135 and MEX3c catalyzed RIG‐I K63‐linked ubiquitin chain and promote RIG‐I activation. USP3, USP21 and CYLD inhibit RIG‐I K63‐linked ubiquitination and activation. MDA5 is K48‐linked ubiquitinated by RNF122 and TRIM13 and then degraded by proteasome. USP14 promotes cGAS signaling by removing K48‐linked ubiquitin chain of cGAS. MyD88 and TRIF are K48‐linked ubiquitinated by Nrdp1 and WWP2 respectively, and then they are sequestered to proteolytic degradation. TRAF6 are inhibited by A20, CYLD and OTUB2 that specially remove TRAF6 K63‐linked ubiquitination. TRAF3 are inhibited by DUBA, OTUB1 and UCHL1 that specilally remove TRAF3 K63‐linked ubiquitination. TRAF3 are also targeted for proteolytic degradation by Triad3‐mediated K48‐linked ubiquitination. MAVS is activated by TRIM31‐medited K63‐linked ubiquitination. RNF5, MARCH5, ITCH and Smurf1/2 catalyze MAVS K48‐linked ubiquitination and induce MAVS degradation by protease. TRIM44 removes ITCH‐induced K48‐linked ubiquitination of MAVS and thus promotes RIG‐I signaling. TRIM32 and TRIM56 promote cGAS signaling by catalyzing K63‐linked ubiquitination of STING. RNF5 catalyzes STING K48‐linked ubiquitination and promotes proteolytic degradation of STING. RNF26 catalyzes STING K11‐linked ubiquitination and inhibit STING degradation. AMFR catalyzes STING K27‐linked ubiquitination and promotes STING activation. TRIM23 promotes NF‐κB and IRF3 activation by adding K27‐linked ubiquitinatin chain to NEMO. HOIL‐1L/HOIP and TRAF7 promote NF‐κB signaling by catalyzing NEMO linear and K29‐linked ubiquitination respectively. Nrdp1 and RNF128 catalyzing TBK1 K63‐linked ubiquitination and thus promoting TBK1 activation. DTX4 induces TBK1 proteolytic degradation by adding K48‐linked ubiquitin chain to it. Pin1, RBCK1, Ro52 and RAUL catalyze IRF3 K48‐linked ubiquitination and promote IRF3 proteolytic degradation.