Changes in Translational Control after Pro-Apoptotic Stress

Charline Lasfargues,Yvan Martineau,Corinne Bousquet,Stéphane Pyronnet

doi:10.3390/ijms14010177

Abstract

In stressed cells, a general decrease in the rate of protein synthesis occurs due to modifications in the activity of translation initiation factors. Compelling data now indicate that these changes also permit a selective post-transcriptional expression of proteins necessary for either cell survival or completion of apoptosis when cells are exposed to severe or prolonged stress. In this review, we summarize the modifications that inhibit the activity of the main canonical translation initiation factors, and the data explaining how certain mRNAs encoding proteins involved in either cell survival or apoptosis can be selectively translated.

Highlights

Stress-induced apoptosis is a physiological mechanism of defense permitting the self-elimination of cells which cannot resolve damage caused by stress
Under mild and/or transient stresses, the inhibition of the global protein synthesis rate is combined with the selective induction of protective proteins which resolve damage caused by stress
Most of the mRNAs identified to date as being translated under stress, despite a general inhibition of protein synthesis, contain specific sequences and encode proteins involved in cell survival

Summary

Introduction

Stress-induced apoptosis is a physiological mechanism of defense permitting the self-elimination of cells which cannot resolve damage caused by stress. Such an anti-tumoral effect is mediated in part through inhibition of protein synthesis since PDCD4 interacts with and sequesters eIF4AI or eIF4AII away from cap-dependent translation initiation complexes [33] Another mechanism that can account for inhibition of eIF4AI or eIF4AII activity in apoptotic cells is their sequestration by fragments of eIF4G generated by caspase cleavage (see below). The destiny of stressed cells (survival or death) is dictated by the activity of pro-survival or pro-apoptotic proteins whose synthesis may paradoxically depend on translational events The synthesis of these proteins is possible due to their mRNAs containing specific cis-acting elements that permit ribosome recruitment, despite the general inhibition of protein synthesis. The translation of HIAP2 mRNA in stressed cells is induced by the presence of another cis-acting element [53]

IRES-Dependent Translation

Conclusions

Conflict of interest