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Apoptosis is related to many diseases and induced by a family of cell death receptors and their ligands. Cell death signals are transduced by death domain containing adapter molecules and members of the caspase family of proteases. These death signals finally cause the degradation of chromosomal DNA by activated DNase. A human DNA fragmentation factor (D) was identified recently which was cleaved by caspase-3 during apoptosis. Mouse homologue of human D was identified as a DNase inhibitor designated ICAD, for inhibitor of caspase-activated DNase. Upon cleavage of D/ICAD, a caspase activated deoxyribonuclease (CAD) is released and activated and eventually causes the degradation of DNA in the nuclei. Therefore, the cleavage of CAD inhibitor molecule D/ICAD, which causes DNase activation and DNA degradation, is the hallmark of apoptotic cell death.