In melanoma cells treated with proinflammatory cytokines, the HECT domain-containing E3 ligase ITCH catalyzes the non-degradative K27-linked ubiquitination of BRAF, which leads to PP2A recruitment, 14-3-3 dissociation, and sustained BRAF/MEK/ERK pathway activation [30]. The gene discussed is ITCH; the disease is melanoma.