Figure 4. The roles of Mst1, Yap and Taz in cytosolic nucleic acid sensing.

dsRNA and dsDNA or DNA-RNA hybrid activate the RIG-1-MAVS and cGAS-STING cytosolic sensors, respectively, leading to the activation of the TBK1-IKKε complex. In contrast to its reported roles in promoting bacteria-induced TLR-IRF3 signaling^70,72, Mst1 was found to directly phosphorylate IRF3, inhibiting IRF3 activity in response to viral infections⁷⁶. Yap and Taz were shown to directly bind TBK1 and block its interaction with other adaptors/substrates⁷⁸. Moreover, Yap was reported to directly interfere with IRF3 dimerization, and IKKε relieves Yap inhibition of IRF3 by directly phosphorylating and targeting Yap for lysosomal degradation⁷⁷. Finally, it was reported that during chronic (>48 hours) viral infection, dimerized IRF3 promotes Yap nuclear translocation and complexes with Yap and Tead in inducing the expression Yap/Tead target genes⁸⁵.