Cell Death and Disease · 2014 · 13 citations · 31 references
Life SciencesCell BiologyMolecular BiologyApoptosisProtein TranslationSignal TransductionApoptosis RegulationCancer Cell SignalingPost-translational RegulationProtein SynthesisProtein TargetingCap-dependent Translation InitiationCellular Membrane PermeabilizationEukaryotic Initiation Factor 4EMembrane BlebbingMembrane PermeabilizationOncogenic TransformationPlasma Membrane PermeabilityPlasma Membrane Permeabilization
The eukaryotic initiation factor eIF4E is essential for cap-dependent initiation of translation in eukaryotes. Abnormal regulation of eIF4E has been implicated in oncogenic transformation. We developed an eIF4E-binding peptide derived from Angel1, a partner of eIF4E that we recently identified. We show here that this peptide fused to a penetratin motif causes drastic and rapid cell death in several epithelial cancer cell lines. This necrotic cell death was characterized by a drop in ATP levels with F-actin network injury being a key step in extensive plasma membrane blebbing and membrane permeabilization. This synthetic eIF4E-binding peptide provides a candidate pharmacophore for a promising new cancer therapy strategy.
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Hierarchical phosphorylation of the translation inhibitor 4E-BP1
Anne‐Claude Gingras, Brian Raught, Steven P. Gygi et al. · Genes & Development · 2001 · 884 citations · Full text