Fas-mediated apoptosis requires the activation of a class of cysteine proteases, which include the ICE family.4 In humans, the ICE family includes CPP-32 and LAP-3 proteases. Triggering of Fas by either the Fas ligand or the anti-Fas antibody rapidly stimulates the proteolytic activity of ICE proteins. Overexpression of the ICE proteins strongly potentiates Fas-mediated cell death; inhibitors of ICE proteins inhibit the apoptotic process. Thus, determining the expression of ICE family proteins is an important marker for monitoring the cell death process.
During normal cell growth stages, the family of Bcl-2 proteins is present as the antagonists of cell death. When the death signal is presented to the cell, the expression of Bcl proteins is down-regulated, which helps the death signal to trigger the activation of the ICE protease family. Consequently, the cell undergoes a characteristic apoptosis process that includes endonuclease activation, cell surface alteration, and cytoskeletal reorganization. Eventually, the cell undergoes phagocytosis. In apoptosis, the dying cell is eliminated although the inflammatory response is not induced.