A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD.
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.
Enari
M
M
Department of Genetics, Osaka University Medical School, Suita, Japan.
Sakahira
H
H
Yokoyama
H
H
Okawa
K
K
Iwamatsu
A
A
Nagata
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D019556:COS Cells; D053148:Caspase 3; D020169:Caspases; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D004926:Escherichia coli; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; C109664:caspase-activated DNase inhibitor; D004247:DNA; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases