The goal of this project is to define how basic cellular mechanisms suppress, activate and execute the process of apoptosis or programmed cell death. Apoptosis is a fundamental component of virtually all aspects of biology, being critical for both developmental and cellular homeostasis in all multi-cellular organisms. Extensive studies worldwide have now implicated either excess or impaired apoptosis in numerous human diseases including cancer, AIDS, autoimmune diseases, sepsis, as well as toxic responses to environmental agents. Additionally, many of the therapies used for the treatment of cancer work by the activation of inherent cellular apoptotic programs. A clear understanding of the cellular mechanisms involved in the control of apoptosis will have considerable impact on human health. Although an enormous literature describes agents that induce apoptosis and the signaling pathways that transduce these death signals, very little information exists on how different signals impinge on the common genetic pathway of apoptosis, particularly from a cell biological perspective.