ITCH targets different signaling pathways in tumor cells.
The arrowhead from ITCH indicates positive regulation of the substrate protein, while the blunt head from ITCH indicates negative regulation of the substrate protein. Blue line indicates a K48-linked polyubiquitination of the substrate, red line indicates a non-proteolytic linkage, while green line indicates the target protein is subjected to endocytic degradation after modified by ITCH. The arrowhead towards ITCH indicate a positive regulation of ITCH E3 ligase activity, while the blunt head towards ITCH indicates negative regulation of ITCH E3 ligase activity.