Model for SCF E3 ligases and ubiquitin-mediated responses to intracellular infection in C. elegans.
Intracellular microsporidia or viral infection triggers the expression of SCF ligase components in C. elegans, including a large number of F-box genes, the cullin cul-6, and Skp1-related genes, skr-3, -4, and -5. Due to the modularity of the SCF ligase complex, many SCF ligases with vast substrate recognition potential may be formed, which could recognize pathogen-derived proteins or host proteins. Ubiquitylation of substrates leads to their degradation by the proteasome or by autophagy, with large substrates such as microsporidia cells, potentially viral particles, and protein aggregates (not shown), targeted by autophagy, and individual pathogen or host proteins by the proteasome. N. parisii parasite cells may be able to suppress or evade ubiquitylation. Both intracellular infection and UPS stress can induce SCF ligase components, and greater demand on the UPS during intracellular infection may contribute to upregulation of SCF ligase components. See Discussion for more details.