CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor

Naohiro Inohara, Takeyoshi Koseki, Shu Chen, Xiaoyu Wu, Gabriel Núñez

Research output: Contribution to journalArticlepeer-review

259 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2526-2533
Number of pages8
JournalEMBO Journal
Volume17
Issue number9
DOIs
Publication statusPublished - 1998 May 1
Externally publishedYes

Keywords

  • Apoptosis
  • CAD
  • Cell death
  • DFF45
  • DNA fragmentation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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