ABSTRACT
Department of Molecular Genetics. Weizmann Institute of Science. Rehovot 76100, Israel.
Programmed cell death is a genetically controlled response of cells to commit suicide. The process, which displays distinctive morphological features, is highly conserved through evolution, and takes place in all nucleated animal cells. It is tightly controlled by environmental stimuli, including extracellular diffusible factors or membrane-bound molecules that mediate cell-cell or cellmatrix interactions, and by non physiological insults to cells such as genotoxic agents. This type of regulation allows the elimination of cells that were either produced in excess during development, have completed their role, are potentially deleterious to the organism, or have become seriously damaged. Programmed cell death is therefore a critical process during embryonic development, tissue remodeling, development of the immune system, and the control of tissue homeostasis (reviewed in Wyllie et al., 1980; Raff, 1992; Schwartz and Osborne, 1993). In addition, several pathologies associated with the disruption of this fundamental process have been characterized. While a decrease in the apoptotic rate is linked in some cases to abnormal expansion in cell number (e.g., in cancer or autoimmune diseases), an abnormal increase in the apoptotic rate is associated with some cell loss disorders (e.g., neurodegenerative diseases) (Thompson, 1995; Barinaga, 1998). The link to cancer has been extensively studied from different aspects, one of which is the apoptotic checkpoint that safeguards cells against hyperproliferative oncogenic signals (Evan and Littlewood, 1998).
