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Science 25 February 2000:
Vol. 287. no. 5457, pp. 1485 - 1489
DOI: 10.1126/science.287.5457.1485
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Reports

Translocation of C. elegans CED-4 to Nuclear Membranes During Programmed Cell Death

Fangli Chen, 1*dagger Bradley M. Hersh, 1* Barbara Conradt, 1ddagger Zheng Zhou, 1 Dieter Riemer, 2 Yosef Gruenbaum, 3 H. Robert Horvitz 1

The Caenorhabditis elegans Bcl-2-like protein CED-9 prevents programmed cell death by antagonizing the Apaf-1-like cell-death activator CED-4. Endogenous CED-9 and CED-4 proteins localized to mitochondria in wild-type embryos, in which most cells survive. By contrast, in embryos in which cells had been induced to die, CED-4 assumed a perinuclear localization. CED-4 translocation induced by the cell-death activator EGL-1 was blocked by a gain-of-function mutation in ced-9 but was not dependent on ced-3 function, suggesting that CED-4 translocation precedes caspase activation and the execution phase of programmed cell death. Thus, a change in the subcellular localization of CED-4 may drive programmed cell death.

1 Howard Hughes Medical Institute, Department of Biology, 68-425, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Department of Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37016 Goettingen, Germany.
3 Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, 91904 Israel.
*   These authors contributed equally to this work.

dagger    Present address: Whitehead Institute, Department of Biology, WI-525, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

ddagger    Present address: Max Planck Institute for Neurobiology, Am Klopferspitz 18A, D-82152 Planegg-Martinsried, Germany.

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