title: A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD.
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.
authors.affiliation: Department of Genetics, Osaka University Medical School, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Enari
authors.forename: H
authors.initials: H
authors.lastname: Sakahira
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: K
authors.initials: K
authors.lastname: Okawa
authors.forename: A
authors.initials: A
authors.lastname: Iwamatsu
authors.forename: S
authors.initials: S
authors.lastname: Nagata
mesh_terms: 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
chemical_list: 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