A CASPASE-ACTIVATED DNASE THAT DEGRADES DNA DURING APOPTOSIS, AND ITSINHIBITOR ICAD

Citation
M. Enari et al., A CASPASE-ACTIVATED DNASE THAT DEGRADES DNA DURING APOPTOSIS, AND ITSINHIBITOR ICAD, Nature, 391(6662), 1998, pp. 43-50
Citations number
44
Categorie Soggetti
Multidisciplinary Sciences
Journal title
NatureACNP
ISSN journal
00280836
Volume
391
Issue
6662
Year of publication
1998
Pages
43 - 50
Database
ISI
SICI code
0028-0836(1998)391:6662<43:ACDTDD>2.0.ZU;2-C
Abstract
The homeostasis of animals is regulated not only by the growth and dif ferentiation of cells, but also by cell death through a process known as apoptosis. Apoptosis is mediated by members of the caspase family o f 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-lo calization signal; ICAD exists in a long and a short form. Recombinant ICAD specifically inhibits CAD-induced degradation of nuclear DMA and its DNase activity. When CAD is expressed with ICAD In COS cells or i n a cell-free system, CAD is produced as a complex with ICAD: treatmen t with caspase 3 releases the DNase activity which causes DNA fragment ation in nuclei. ICAD therefore seems to function as a chaperone for C AD during its synthesis, remaining complexed with CAD to inhibit its D Nase activity; caspases activated by apoptotic stimuli then cleave ICA D, allowing CAD to enter the nucleus and degrade chromosomal DNA.