The eukaryotic initiation factor 4E-binding proteins and apoptosis

Proud, C.G. (2005) The eukaryotic initiation factor 4E-binding proteins and apoptosis. Cell Death and Differentiation, 12, 541-546. (doi:10.1038/sj.cdd.4401588).

Record type: Article

Abstract

Eukaryotic initiation factor 4E (eIF4E) is a key component of the translational machinery that is required for cap-dependent translation. It also exerts antiapoptotic effects and can transform cells. However, some mRNAs do not require eIF4E as they are translated by mechanisms involving internal ribosome entry. Overexpression of eIF4E is associated with cell transformation and can protect cells against apoptosis. eIF4E's function in cap-dependent translation is blocked by eIF4E-binding proteins, such as 4E-BP1. 4E-BP1 is inhibited by phosphorylation mediated through the mammalian target of rapamycin pathway, which can exert antiapoptotic effects. In response to cell stresses, for example DNA damage, 4E-BP1 undergoes dephosphorylation favouring its binding to eIF4E and thus inhibiting cap-dependent translation. Furthermore, in apoptotic cells, 4E-BP1 undergoes caspase-dependent cleavage, which removes an important regulatory motif and so causes its dephosphorylation and binding to eIF4E. These events impair cap-dependent translation and are likely to lead to a switch in protein synthesis to favour cap-independent mRNAs. Synthesis of several proteins that have pro- or antiapoptotic functions is thereby enhanced, altering the balance of apoptotic signaling.

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