Two recent papers describe the processes involved in the final stages of apoptotic cell death. During apoptosis, enzymes known as caspases break down cellular proteins, causing severe morphological changes and cell shrinkage. In the final stages, the chromosomal DNA is cut up by a DNase enzyme, the identity of which has remained a mystery. Shigekazu Nagata from Osaka University Medical School, Japan, and colleagues now report the purification and cloning of a novel caspase-3 activated DNase (CAD) and its inhibitor (ICAD). The enzyme CAD cleaves chromosomal DNA in the final stage of apoptosis. Its inhibitor ICAD appears to act as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity until it is triggered by appropriate apoptotic stimuli. It turns out that CAD does not control apoptosis itself. When ICAD is overexpressed, removing CAD activity, cell death by apoptosis could still be induced, probably as a result of cleavage of various cellular proteins by caspases.—June Kinoshita
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- Sakahira H, Enari M, Nagata S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature. 1998 Jan 1;391(6662):96-9. PubMed.
- Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature. 1998 Jan 1;391(6662):43-50. PubMed.