It is noteworthy that although TNFα promoted BRAF ubiquitination in BRAFV600E-expressing 1205Lu melanoma cells (Supplementary Fig. 6n), the treatment only moderately affected MEK/ERK activities (Supplementary Fig. 6o), which is consistent with the results that p-MEK/p-ERK levels were insensitive to ITCH knockdown (Supplementary Fig. 4h). Here, TNF is linked to melanoma.