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Role of CED-4 in the activation of CED-3

Author

Listed:
  • Arul M. Chinnaiyan

    (University of Michigan Medical School)

  • Divya Chaudhary

    (University of Michigan Medical School)

  • Karen O'Rourke

    (University of Michigan Medical School)

  • Eugene V. Koonin

    (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A)

  • Vishva M. Dixit

    (Genentech, Inc., 1 DNA Way, M/S-40)

Abstract

Genetic analyses of the nematode Caenorhabditis elegans have identified three core components of the cell-death apparatus1. CED-3 and CED-4 promote, whereas CED-9 inhibits cell death. Recent studies indicate that CED-4 might interact independently with CED-3 and CED-9, forming the crux of a multicomponent death complex2. But except for its role as an adaptor molecule, little is known about CED-4 function. A clue came with the observation that mutation of the phosphate-binding loop (P-loop) of CED-4 disrupts its ability to induce chromatin condensation in yeast3. Further, a P-loop mutant of CED-4 (CED-4K165R) fails to process CED-3 in vivo, both in insect4 and mammalian cells (unpublished). We now confirm that CED-4 induces CED-3 activation and subsequent apoptosis, and that the process requires binding of ATP.

Suggested Citation

  • Arul M. Chinnaiyan & Divya Chaudhary & Karen O'Rourke & Eugene V. Koonin & Vishva M. Dixit, 1997. "Role of CED-4 in the activation of CED-3," Nature, Nature, vol. 388(6644), pages 728-729, August.
    • Handle: RePEc:nat:nature:v:388:y:1997:i:6644:d:10.1038_41913
    DOI: 10.1038/41913
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