Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release

Shunan Li, Tasaburo Takasu, David M Perlman, Mark S. Peterson, David Burrichter, Svetlana V Avdulov, Peter B Bitterman, Vitaly A Polunovsky

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Eukaryotic translation initiation factor 4E (eIF4E) markedly reduces cellular susceptibility to apoptosis. However, the mechanism by which the translation apparatus operates on the cellular apoptotic machinery remains uncertain. Here we show that eIF4E-mediated rescue from Myc-dependent apoptosis is accompanied by inhibition of mitochondrial cytochrome c release. Experiments achieving gain and loss of function demonstrate that eIF4E-mediated rescue is governed by pretranslational and translational activation of bcl-x as well as by additional intermediates acting directly on, or upstream of, the mitochondria. Thus, our data trace a pathway controlling apoptotic susceptibility that begins with the activity state of the protein synthesis machinery and leads to interdiction of the apoptotic program at the mitochondrial checkpoint.

Original languageEnglish (US)
Pages (from-to)3015-3022
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number5
DOIs
StatePublished - Jan 31 2003

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