Natural cellular inhibitors of caspases.

The crucial role of cell death in many diseases is obvious and has spurred intense research to understand the regulation of apoptotic pathways. Caspase activation is central to many of the apoptotic pathways. In recent years, the study of the regulation of caspase activation and activity in various cell lines and in diseases has revealed highly complex mechanisms regulating cell survival or cell death. In this review, the major natural cellular anticaspase factors are described with particular attention to the inhibitors that prevent active caspases from committing the cell to irreversible destruction. The major group of caspase inhibitors known is the inhibitor of apoptosis proteins (IAP) and this review describes the characteristics of IAP, regulation of IAP expression, and mechanisms of action of IAP. However, other proteins including Bcl-2 family members, heat shock proteins, caspase-like decoy, calpains and proteases, and lipid moieties in the form of phosphoinositides also can function as caspase inhibitors. The current knowledge of the inhibition of these non-IAP factors is described herein.