The opposing roles of the Akt and c-Myc signalling pathways in survival from CD95-mediated apoptosis (original) (raw)

Oncogene volume 17, pages 2811–2818 (1998)Cite this article

Abstract

Expression of the proto-oncogene c-myc stimulates cell proliferation in the presence of the appropriate survival factors and triggers apoptosis in their absence; this dual capacity ensures that cell growth is restricted to the correct paracrine environment and is thereby strictly controlled. Recently our laboratory demonstrated that c-Myc-induced apoptosis requires the CD95 death receptor pathway and that insulin-like growth factor (IGF-1) signalling suppresses this killing. To investigate further the links between c-Myc and IGF-1 pathways in CD95-induced apoptosis, we examined the effects of c-Myc and a downstream IGF-1 survival kinase, Akt, on killing mediated by CD95 and its recruited effector proteins (FADD and caspase-8). Here, we show that c-Myc activation does not exacerbate killing induced by FADD or pro-caspase-8, which narrows the point at which c-Myc exerts its action downstream of the interaction of CD95 with its ligand and upstream of FADD. We show further that activated Akt suppresses CD95-induced apoptosis and that Akt exerts its activity at a point downstream of FADD but upstream of caspase-8. These results restrict the possible mechanisms by which CD95-induced apoptosis is modulated by death signals and survival factors.

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Authors and Affiliations

  1. Biochemistry of the Cell Nucleus Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK
    Jennifer L Rohn, Anne-Odile Hueber, Nicola J McCarthy, Debbie Lyon & Gerard I Evan
  2. Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, Madrid, 28040, Spain
    Paloma Navarro
  3. Laboratory for Physiological Chemistry, Utrecht University, Universiteitsweg 100, De Uithof, Utrecht, The Netherlands
    Boudewijn M Th Burgering

Authors

  1. Jennifer L Rohn
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  2. Anne-Odile Hueber
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  3. Nicola J McCarthy
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  4. Debbie Lyon
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  5. Paloma Navarro
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  6. Boudewijn M Th Burgering
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  7. Gerard I Evan
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Rohn, J., Hueber, AO., McCarthy, N. et al. The opposing roles of the Akt and c-Myc signalling pathways in survival from CD95-mediated apoptosis.Oncogene 17, 2811–2818 (1998). https://doi.org/10.1038/sj.onc.1202393

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