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. Author manuscript; available in PMC: 2014 Aug 1.
Published in final edited form as: Curr Mol Med. 2013 Aug;13(7):1110–1121. doi: 10.2174/1566524011313070006

Figure 1. Schematic of TLR4 negative regulators.

Figure 1

Arrows indicate sites of inhibition. Sigirr inhibits the initiation of this pathway by preventing TLR4's interaction with MyD88. IRAK-M and TOLLIP both prevent the dissociation of IRAKs from MyD88. TRIAD3A has several mechanisms of inhibition by interacting within the Toll-interleukin-1 receptor domains of TIRAP, TRIF, and RIP1. Overexpression of TRIAD3 also degrades TLR4. A20 is a de-ubiquitinating enzyme which removes ubiquitin moieties from TRAF6 to prevent downstream signaling. miR-21 is a microRNA targeting the protein PDCD4 and preventing activation of NF-κB. VACV A52R is a viral protein that prevents the formation of IRAK TRAF6 complexes. TANK prevents the ubiquitination of TRAF6 suppressing further downstream signaling. ST2825 a synthetic compound, prevents MyD88's association with IRAKs. DUBA cleaves polyubiquitin chains from TRAF3 to suppress type I interferons.