In agreement with our previous finding that TRAIL-R2 is the dominant TRAIL death receptor in melanoma cells [9,10], inhibition of the interaction of TRAIL with TRAIL-R2, but not with TRAIL-R1, markedly blocked sensitization of melanoma cells to TRAIL-induced apoptosis by 2-DG, indicating that up-regulation of TRAIL-R2 was the main cause of sensitization of melanoma cells to TRAIL-induced apoptosis, even though both TRAIL-R1 and -R2 were increased by 2-DG. The gene discussed is TNFRSF10A; the disease is melanoma.