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A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD

来自 EBSCO

阅读量：

529

作者：

M Enari，H Sakahira，H Yokoyama，K Okawa，A Iwamatsu，S Nagata

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摘要：

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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关键词：

Animals Humans Mice COS Cells Tumor Cells, Cultured Escherichia coli Deoxyribonucleases Cysteine Endopeptidases Caspases DNA

DOI：

10.1038/34112

被引量：

8579

年份：

1998

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来源期刊

Nature
01 January 1998

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