ABSTRACT
Apoptosis or programmed cell death (PCD) is a genetically controlled process whereby cells die in response to environmental or developmental cues. The morphological characteristics of apoptosis include cytoplasmic blebbing, chromatin condensation and nucleosomal fragmentation (Wyllie, 1980). Dead cells are rapidly phagocytized to prevent damage to neighboring cells. Regulation of apoptosis is critical for normal development and tissue homeostasis and disruption of this process can have severe consequences (Jacobson et al., 1997). Too much cell death may produce neurodegenerative diseases and impaired development, while insufficient cell death can lead to increased susceptibility to cancer and sustained viral infection. Progress has been made in the past decade to identify many of the basic components that contribute to apoptosis, including transcriptional mediators, membranebound receptors (e.g. TNF-α receptor and Fas), Bcl-2 family members, kinases/ phosphatases, and cysteine proteases (White, 1996). Some of these proteins have been evolutionarily conserved from nematodes to mammals (Steller, 1995). bcl-2 was one of the first genes shown to regulate apoptosis (Hockenbery et al., 1990) and can inhibit apoptosis in a wide variety of systems (White, 1996). bcl-2 belongs to a growing family of genes that can either positively or negatively regulate apoptosis. One of these gene products, Bax, binds to Bcl-2 and antagonizes its ability to block apoptosis (Oltvai et al., 1993). Another critical element of the apoptotic process is the activation of cysteine proteases, which are currently referred to as caspases (Alnemri et al., 1996; Rao and White, 1997). In general, the caspases act downstream of Bcl-2-like proteins to induce apoptosis. Thus, the regulation of apoptosis appears to be a precarious balance between factors that promote survival and those responsible for initiating and executing cellular suicide. In this review, we present an overview of the basic components of apoptosis, like Bcl-2 and caspases, and how they are believed to function in this process.
