A recent analysis (1) suggests that caspase-mediated cleavages play three important roles during apoptosis. First, they turn off activities required for cell survival, including extracellular matrix-initiated signalling pathways, DNA repair, and RNA synthesis. Second, they turn on activities that lead to cellular disruption. Among these are gelsolin, which disrupts the actin cytoskeleton; the caspase-activated DNase CAD/CPAN/DFF40, which contributes to internucleosomal DNA degradation; and a variety of protein kinases. Third, they diminish the integrity of certain critical structural components of the cell, including cytokeratin 18, fodrin, the lamins, and the nuclear/mitotic apparatus protein (NuMA). Collectively, these cleavages give rise to the biochemical and morphological changes that comprise the process of apoptosis.
Two major approaches have evolved for studying the effects of caspase activation on this process. Each of these is briefly discussed below.
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