THE BCL-2 PROTEIN FAMILY - ARBITERS OF CELL-SURVIVAL

Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis , the cell suicide program critical for development, tissue homeostasi s, and protection against pathogens. Those most similar to Bcl-2 promo te cell survival by inhibiting adapters needed for activation of the p roteases (caspases) that dismantle the cell. More distant relatives in stead promote apoptosis, apparently through mechanisms that include di splacing the adapters from the pro-survival proteins. Thus, for many b ut not all apoptotic signals, the balance between these competing acti vities determines cell fate. Bcl-2 family members are essential for ma intenance of major organ systems, and mutations affecting them are imp licated in cancer.