Signaling pathway for apoptosis: A racetrack for life or death

Apoptosis, or programmed cell death, is a gene-directed mechanism activated as a suicidal event to gel rid of excess, damaged, or infected cells. The recent astounding pace of research in this area has expanded our horizon of understanding that this mechanism is regulated largely by pro- and anti-ap optosis factors acting for or against the final death event. The driving fo rce behind these factors, either pro-apoptosis or pro-survival, is largely determined by signal transduction pathways, starling with the initiation of a death signal at the plasma membrane, and following through a complex cyt oplasmic network before reaching the end point of cell demise. Enmeshed in this intricate cytoplasmic network are many checkpoints, where complexes of pro- and anti-apoptosis factors function to facilitate or deter the death signals. The culmination of the balancing act between these two camps of fa ctors at these signal transduction checkpoints may then result in the final decision to die or to live. Thus, the eventual death of a cell may require successful passage through all the checkpoints, a mechanism Nature has pro vided as a safeguard to prevent erroneous triggering of death. With the adv ent of a new biotechnology revolution at the dawn of the new millenium Lye look forward to an exciting era when we can gain fuller understanding of th e operation of all these checkpoints. Ultimately this gain will pave the wa y to control the apoptosis event at the checkpoints, and to support the org anism's functionality as long as possible. (C) 1999 Wiley-Liss, Inc.