Checkpoints of dueling dimers foil death wishes

Recent evidence has emphasized the indispensable role of programmed cell death in the development and maintenance of homeostasis within all multicellular organisms. Genetic and molecular analysis from nematodes to humans has indicated that cellular suicide is highly conserved. Thus, it appears that the evolutionary switch from a unicellular to a multicellular existence hinged in part upon the creation of a regulated cell suicide response. From an individual cell's point of view, signals received from its environment can prompt the ultimate sacrifice: its own demise. The capacity to carry out apoptosis appears to be inherent to most (if not all) cells that depend upon an extracellular milieu of survival factors or cell-cell contact molecules for their viability. Yet it is increasingly evident that the decision to die is not solely determined by extracellular signals. In a number of biological systems, the degree of sensitivity to a given death stimulus is cell-type specific. For example, CD4 super(+)CD8 super(+) cortical thymocytes are exquisitely sensitive to a wide variety of apoptotic stimuli, while the more mature medullary thymocytes are resistant. Similarly, in the Drosophila eye, a given signal can effectively rescue cells from apoptosis at one developmental stage, but not at another. The observations imply the existence of an autonomous regulation of the apoptotic program.