Molecular machinery and signaling events in apoptosis

Apoptosis is a process of major biomedical interest, since its ineffectiveness or inappropriate activation appears to be involved in the pathogenesis of a broad variety of human diseases (neoplasia, autoimmune disorders, viral and neurodegenerative diseases, to name a few). On this topic, extensive experimental work has allowed in the past years the clarification of the complex biochemical machinery that commits a cell to apoptosis and executes the death program. As to the signaling mechanisms, it is now evident that apoptosis can be initiated by different stimuli and/or genetic programs that are differentially decoded inside the cell. While the past years have witnessed a major advancement on this topic, much still needs to be Learned of the cross-talk between the various signaling pathways involved in decoding the apoptotic stimuli, as well as the activation of other cel functions. In this review we first describe the properties and activation mechanisms of the caspases, the effector proteases of apoptosis. in the second part we discuss the current evidence for the involvement of calcium, the ubiquitous second-messenger decoding a wide variety of physiological stimuli, and highlight the potential targets of the apoptotic calcium signal. Drug Dev. Res. 52:558-570, 2001. (C) 2002 Wiley-Liss, Inc.