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.