A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
M Enari, H Sakahira, H Yokoyama, K Okawa… - Nature, 1998 - nature.com
M Enari, H Sakahira, H Yokoyama, K Okawa, A Iwamatsu, S Nagata
Nature, 1998•nature.comThe homeostasis of animals is regulated not only by the growth and differentiation of cells,
but also by cell death through a process known as apoptosis. Apoptosis is mediated by
members of the caspase family of proteases, and eventually causes the degradation of
chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD)
have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a
protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long …
but also by cell death through a process known as apoptosis. Apoptosis is mediated by
members of the caspase family of proteases, and eventually causes the degradation of
chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD)
have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a
protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long …
Abstract
The homeostasis of animals is regulated not only by the growth and differentiation of cells, but also by cell death through a process known as apoptosis. Apoptosis is mediated by members of the caspase family of proteases, and eventually causes the degradation of chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long and a short form. Recombinant ICAD specifically inhibits CAD-induced degradation of nuclear DNA and its DNase activity. When CAD is expressed with ICAD in COS cells or in a cell-free system, CAD is produced as a complex with ICAD: treatment with caspase 3 releases the DNase activity which causes DNA fragmentation in nuclei. ICAD therefore seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity; caspases activated by apoptotic stimuli then cleave ICAD, allowing CAD to enter the nucleus and degrade chromosomal DNA.
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