FIGURE 12.

Proposed model for βarr2-mediated regulation of ubiquitin-dependent NFκB signaling. Activation of TLR4 triggers ubiquitination of βarr2 and TRAF6. Ubiquitinated βarr2 scaffolds USP20 to TRAF6 with low avidity. Therefore, when βarr2 is ubiquitinated, there is less deubiquitination of TRAF6 and greater NFκB signaling. However, after it is deubiquitinated by USP20, βarr2 scaffolds USP20 to TRAF6 with high avidity. Consequently, USP20-mediated TRAF6 deubiquitination and inhibition of NFκB signaling transpires.