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Cited by 335

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c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release

Open access
Juin, P., Hueber, A.-O., Littlewood, T., Evan, G.·1999·Genes & Development

Abstract

Expression of c-Myc sensitizes cells to a wide range of pro-apoptotic stimuli. We here show that this pro-apoptotic effect is mediated through release of mitochondrial holocytochrome c into the cytosol. First, activation of c-Myc triggers release of cytochrome c from mitochondria. This release is caspase-independent and blocked by the survival factor IGF-1. Second, c-Myc-induced apoptosis is blocked by microinjection of anticytochrome c antibody. In addition, we show that microinjection of holocytochrome c mimics the effect of c-Myc activation, sensitizing cells to DNA damage and to the CD95 pathway. Both p53 and CD95/Fas signaling have been implicated in c-Myc-induced apoptosis but neither was required for c-Myc-induced cytochrome c release. Nonetheless, inhibition of CD95 signaling in fibroblasts did prevent c-Myc-induced apoptosis, apparently by obstructing the ability of cytosolic cytochrome c to activate caspases. We conclude that c-Myc promotes apoptosis by causing the release of cytochrome c, but the ability of cytochrome c to activate apoptosis is critically dependent upon other signals.

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Metadata

Authors
Juin, P., Hueber, A.-O., Littlewood, T., & Evan, G.
Venue
Genes & Development
Published
1999-06-01
Volume
13
Issue
11
Pages
1367-1381
ISSN
0890-9369 (ISSN-L)
OpenAlex
W2132625535
Cited by
335
References
2
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release. https://app.cochat.ai/papers/10.1101/gad.13.11.1367
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Juin, P., Hueber, A.-O., Littlewood, T., & Evan, G. (1999). c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release. Genes & Development. https://doi.org/10.1101/gad.13.11.1367

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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