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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202393
Keywords
This article is cited by
-
Cell death proteins as markers of early postmortem interval
Cellular and Molecular Life Sciences (2014)
-
Molecular targets of opiate drug abuse in neuro AIDS
Neurotoxicity Research (2005)
-
Sustained Akt/PKB activation and transient attenuation of c-jun N-Terminal kinase in the inhibition of apoptosis by IGF-1 in vascular smooth muscle cells
Apoptosis (2005)
-
Prolactin induces c-Myc expression and cell survival through activation of Src/Akt pathway in lymphoid cells
Oncogene (2004)
-
N-Myc overexpression leads to decreased β1 integrin expression and increased apoptosis in human neuroblastoma cells
Oncogene (2003)