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Science 9 February 1996:
Vol. 271. no. 5250, pp. 808 - 810
DOI: 10.1126/science.271.5250.808
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Reports

Requirement of an ICE-Like Protease for Induction of Apoptosis and Ceramide Generation by REAPER

Gijsbertus J. Pronk (1),  Kevin Ramer,  Payman Amiri,  Lewis T. Williams

Genetic studies indicated that the Drosophila melanogaster protein REAPER (RPR) controls apoptosis during embryo development. Induction of RPR expression in Drosophila Schneider cells rapidly stimulated apoptosis. RPR-mediated apoptosis was blocked by N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk), which suggests that an interleukin-1beta converting enzyme (ICE)-like protease is required for RPR function. RPR-induced apoptosis was associated with increased ceramide production that was also blocked by Z-VAD-fmk, which suggests that ceramide generation requires an ICE-like protease as well. Thus, the intracellular RPR protein uses cell death signaling pathways similar to those used by the vertebrate transmembrane receptors Fas (CD95) and tumor necrosis factor receptor type 1.


G. J. Pronk and P. Amiri, Chiron Corporation, Emeryville, CA 94608, USA.
K. Ramer, Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA.
L. T. Williams, Chiron Corporation, Emeryville, CA 94608, and Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA.
(1) To whom correspondence should be addressed at Chiron Corporation, Room M348, 4560 Horton Street, Emeryville, CA 94608, USA.


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Processing/Activation of At Least Four Interleukin-1{beta} Converting Enzyme-like Proteases Occurs during the Execution Phase of Apoptosis in Human Monocytic Tumor Cells.
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J. Cell Biol. 137, 469-479
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K. Orth and V. M. Dixit (1997)
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G. S. Dbaibo, D. K. Perry, C. J. Gamard, R. Platt, G. G. Poirier, L. M. Obeid, and Y. A. Hannun (1997)
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M. McCarthy, L. Rubin, and K. Philpott (1997)
J. Cell Sci. 110, 2165-2173
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Functions of Ceramide in Coordinating Cellular Responses to Stress.
Y. A. Hannun (1996)
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Different Interleukin-1{beta} Converting Enzyme (ICE) Family Protease Requirements for the Apoptotic Death of T Lymphocytes Triggered by Diverse Stimuli.
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A Link between Apoptosis and Degree of Phosphorylation of High Mobility Group A1a Protein in Leukemic Cells.
F. Diana, R. Sgarra, G. Manfioletti, A. Rustighi, D. Poletto, M. T. Sciortino, A. Mastino, and V. Giancotti (2001)
J. Biol. Chem. 276, 11354-11361
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Caspase-dependent Cleavage of ErbB-2 by Geldanamycin and Staurosporin.
O. Tikhomirov and G. Carpenter (2001)
J. Biol. Chem. 276, 33675-33680
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Identification and Developmental Expression of Inhibitor of Caspase-activated DNase (ICAD) in Drosophila melanogaster.
N. Mukae, H. Yokoyama, T. Yokokura, Y. Sakoyama, H. Sakahira, and S. Nagata (2000)
J. Biol. Chem. 275, 21402-21408
   Abstract »    Full Text »    PDF »


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