Skip to main content
. 2020 Dec 15;8(2):2002484. doi: 10.1002/advs.202002484

Figure 3.

Figure 3

DUBs in TLR mediated signaling cascades. TLR2/4 and TLR7/8/9 recruit MyD88 and IRAKs, forming the MyD88 signaling complex. TRAF6 is subsequently recruited, synthesizing K63‐linked polyubiquitin chains that act as a scaffold for recruiting TAK1 and IKK complexes. TAK1 phosphorylates IKKbeta and activates IKK complex. TAK1 also activates the MAPK kinase family. Activation of IKK and MAPKs leads to the activation of transcription factors NF‐kappaB and AP1, respectively, and induces proinflammatory cytokines. TLR7/8/9 can initiate the activation of IRF5 and IRF7, whereas TLR3 recruits TRIF. Activated TRIF recruits both TRAF3 and RIP1. TRAF3 is crucial for recruiting the TBK1 complex following K63‐linked polyubiquitination. TBK1 recruits and phosphorylates IRF3 and promotes IFN‐beta production. DUBs that upregulate or downregulate the signaling are shown with purple or green back color, respectively. A detailed list of the target proteins and DUBs is included in Table 1.