THE C-MYC PROTEIN INDUCES CELL-CYCLE PROGRESSION AND APOPTOSIS THROUGH DIMERIZATION WITH MAX

The c-Myc protein (Myc) is involved in cellular transformation and mit ogenesis, but is also a potent inducer of programmed cell death, or ap optosis. Whether these apparently opposite functions are mediated thro ugh common or distinct molecular mechanisms remains unclear. Myc and i ts partner protein, Max, dimerize and bind DNA in vitro and in vivo th rough basic/helix-loop-helix/leucine zipper motifs (bHLH-LZ). By using complementary leucine zipper mutants (termed MycEG and MaxEG), which dimerize efficiently with each other but not with their wild-type part ners, we demonstrate that both cell cycle progression and apoptosis in nontransformed rodent fibroblasts are induced by Myc-Max dimers. MycE G or MaxEG alone are inactive, but co-expression restores ability to p revent withdrawal from the cell cycle and to induce cell death upon re moval of growth factors. Thus, Myc can control two alternative cell fa tes through dimerization with a single partner, Max.