Fig. 6. A graphical illustration of p62-dependent caspase-8 activation upon irradiation.

Synthetic p62-ZZ ligands, such as YOK1104, induce p62 self-oligomerization, its interaction with LC3, and autophagosome biogenesis. Ionizing radiation treatment induces ubiquitination of caspase-8. A synthetic ligand-activated p62 via its ZZ domain promotes aggregation of ubiquitinated caspase-8 into aggresomes-like structures leading to apoptosis.