Fig. 8: A schematic model showing how ARRB2 regulates lung cancer progression by regulating the TRAF6-TAB2 signaling axis for the activation of NF-κB and the TRAF6-BECN1 signaling axis for the induction of autophagy.

Engagement of TLR3/TLR4 can induce the activation of NF-κB through the TRAF6-TAB2 signaling axis (left, green) and autophagy through the TRAF6-BECN1 signaling axis (right, blue), eventually facilitating lung cancer progression. ARRB2 interacts with the coiled-coil domain of TRAF6 and inhibits TRAF6 auto-ubiquitination and TRAF6-TAB2 association for the activation of NF-κB (left, pink line). Simultaneously, ARRB2 interrupts the interaction between TRAF6 and BECN1 and inhibits BECN1 ubiquitination for autophagy induction (right, pink line). Consequently, ARRB2 inhibits lung cancer progression regulated by two signaling axes, TRAF6-TAB2 signaling axis for NF-κB activation and TRAF6-BECN1 signaling axis for autophagy induction, in response to TLR3 and TLR4 stimulation (center, pink line).