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PMID:9564035
| Citation |
Inohara, N, Koseki, T, Chen, S, Wu, X and Núñez, G (1998) CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor. EMBO J. 17:2526-33 |
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| Abstract |
DFF45 is a subunit of the DNA fragmentation factor (DFF) that is cleaved by caspase-3 during apoptosis. However, the mechanism by which DFF45 regulates apoptotic cell death remains poorly understood. Here we report the identification and characterization of two mammalian genes, CIDE-A and CIDE-B, encoding highly related proteins with homology to the N-terminal region of DFF45. CIDE-A and CIDE-B were found to activate apoptosis in mammalian cells, which was inhibited by DFF45 but not by caspase inhibitors. Expression of CIDE-A induced DNA fragmentation in 293T cells, which was inhibited by DFF45, further suggesting that DFF45 inhibits the apoptotic activities of CIDEs. In addition to mammalian CIDE-A and CIDE-B, we identified DREP-1, a Drosophila melanogaster homolog of DFF45 that could inhibit CIDE-A-mediated apoptosis. Mutant analysis revealed that the C-terminal region of CIDE-A was necessary and sufficient for killing whereas the region with homology to DFF45 located in the N-terminus was required for DFF45 to inhibit CIDE-A-induced apoptosis. CD95/Fas-mediated apoptosis was enhanced by CIDEs but inhibited by DFF45. These studies suggest that DFF45 is evolutionarily conserved and implicate CIDEs as DFF45-inhibitable effectors that promote cell death and DNA fragmentation. |
| Links |
PubMed PMC1170594 Online version:10.1093/emboj/17.9.2526 |
| Keywords |
Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins; Cell Line; DNA Fragmentation; Drosophila melanogaster/physiology; Humans; Macromolecular Substances; Mammals; Mice; Molecular Sequence Data; Molecular Weight; Protein Biosynthesis; Proteins/chemistry; Proteins/genetics; Recombinant Proteins/biosynthesis; Recombinant Proteins/chemistry; Sequence Alignment; Sequence Homology, Amino Acid; Transfection |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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