In BRAF(V600E)-harboring melanoma, metabolic stress-activated AMPK phosphorylates the C-terminal 14-3-3 binding site of BRAF and promotes the intramolecular association of a single BRAF molecule with a 14-3-3 dimer [233], which breaks the BRAF/KSR heterodimer and thus inhibits MAPK signaling [230], although whether active AMPK phosphorylates the N-terminal 14-3-3 binding site of BRAF under this condition needs further investigation (Fig. 4b). The gene discussed is BRAF; the disease is melanoma.