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Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis

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Abstract

THE induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown1. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide2,3, is thought to mediate apoptosis in response to tumour-necrosis factor (TNF)-α2,3, to Fas ligand4 and to X-rays5. It is not known whether it plays a role in the stimulation of other forms of stress-induced apoptosis. Given that environmental stresses also stimulate a stress-activated protein kinase (SAPK/JNK) 6–12, the sphingomyelin and SAPK/ JNK signalling systems may be coordinated in induction of apoptosis. Here we report that ceramide initiates apoptosis through the SAPK cascade and provide evidence for a signalling mechanism that integrates cytokine- and stress-activated apoptosis.

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Author notes

  1. Marcel Verheij

    Present address: Department of Radiation Therapy, Antoni v. Leeuwenhoekhuis/The Netherlands Cancer Institute, Amsterdam, The Netherlands

Authors and Affiliations

  1. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    Marcel Verheij, Adriana Haimovitz-Friedman & Zvi Fuks

  2. Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA

    Ron Bose, Xin Hua Lin, Bei Yao & Richard N. Kolesnick

  3. Department of Medicine, Division of Hematology–Oncology, Medical College of Virginia, 1101 East Marshall Street, Richmond, Virginia, 23298, USA

    W. David Jarvis & Steven Grant

  4. Biomarkers and Prevention Research Branch, Division of Cancer Prevention and Control, National Cancer Institute, 9610 Medical Center Drive, Rockville, Maryland, 20850, USA

    Michael J. Birrer & Eva Szabo

  5. Division of Hematology–Oncology, Children's Hospital and Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Howard Hughes Medical Institute, Children's Hospital, 300 Longwood Avenue, Enders 780, Boston, Massachusetts, 02115, USA

    Leonard I. Zon

  6. Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, 149 13th Street, Charlestown, Massachusetts, 02129, USA

    John M. Kyriakis

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  1. Marcel Verheij
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  2. Ron Bose
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  3. Xin Hua Lin
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  4. Bei Yao
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  5. W. David Jarvis
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  6. Steven Grant
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  7. Michael J. Birrer
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  8. Eva Szabo
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  9. Leonard I. Zon
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  10. John M. Kyriakis
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  11. Adriana Haimovitz-Friedman
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  12. Zvi Fuks
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  13. Richard N. Kolesnick
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Verheij, M., Bose, R., Hua Lin, X. et al. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380, 75–79 (1996). https://doi.org/10.1038/380075a0

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  • DOI: https://doi.org/10.1038/380075a0

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