Synergistic interaction of BCL2 and Myc.

Genes involved in these processes, which are deregulated by IGtranslocations, are shown in yellow. BCL2: Central to the control of apoptosis is the release of cytochrome c from the mitochondrion, resulting in activation of procaspase 9. BCL2 prevents this by maintaining ADP/ATP exchange through the voltage-dependent anion channel (VDAC) within the mitochondrial membrane, inhibiting H⁺ accumulation in the intermembrane space and subsequent cytochrome c release. However, BCL2 also inhibits proliferation by promoting cell cycle arrest. Myc: Myc mediates both proliferation and apoptosis. Blocking of Myc-induced apoptosis by genetic events, such as BCL2 overexpression or alterations in the p19 (ARF)–Mdm2–p53 pathway, results in unrestrained proliferation.