ABSTRACT

Apoptosis refers to a lethal program that is activated in cells when they are in­ duced to commit suicide. When this program is activated, a highly characteris­ tic series of events takes place. These events include the activation of the caspases, a family of cysteine proteases that cleave their substrates on the carboxyl side of an aspartate residue; the cleavage of the caspase targets, which include poly(ADP-ribose) polymerase, actin, the chromosomal protein lamin B, a subunit of DNA-dependent protein kinase (1), and a subunit of the DNA replication com­ plex C, among others; the cleavage of the genome into fragments whose lengths are integral multiples of ~200 bp, which is the amount of DNA found in a nucleosome; the transfer of phosphatidylserine from the inner to the outer plasma mem­ brane leaflet; the activation of tissue transglutaminase and the cross-linking of actin; acidification of the cytosol by ~0.5 pH units; and finally the disintegration of the cell by the formation of blebs that break off and float away, to be disposed of by mononuclear phagocytes which recognize phosphatidylserine and certain adhesion proteins that appear on the surface of the blebs. The net effect is the destruction of the cell without loss of its contents into the extracellular environ­ ment.