Notably, compared with WT-ITCH-expressing cells, melanoma cells harboring a JNK phosphorylation-deficient 3A (S199A/T222A/S232A)-ITCH exhibited a significant reduction of both BRAF and c-Jun ubiquitination upon TNFα stimulation, and were unresponsive to TNFα-triggered MEK/ERK activation (Supplementary Fig. 7c, d). Here, MAPK8 is linked to melanoma.