Apoptosis, a highly controlled mode of cell death, is utilized to eliminate superfluous, aged, injured or infected cells from the body. Caspases, a family of aspartic acid-specific proteases, are the major effectors of apoptosis. To curtail their activity, caspases are normally synthesized as inactive precursors, but become activated at the onset of apoptosis by activation signals. Once active, caspases preside over the ordered dismantling of the cell through restricted proteolysis of hundreds of substrate proteins. Over the last 10 years, intense research has focused upon the pathways that control caspase activation. Although some, such as the apoptosome and death receptor-mediated pathways to caspase activation, are well established, others are less clearly defined. In this review, we discuss current perspectives concerning the diverse pathways to caspase activation.

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