Initiation Factor eIF2α Phosphorylation in Stress Responses and Apoptosis

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Abstract

Protein synthesis in eukaryotes is a complex process which can be regulated at many points in the pathway. In recent years it has become clear that both the overall rate of translation and the relative rates of synthesis of individual proteins can be controlled post-transcriptionally through changes in the activities or levels of a small number of key components, and that such regulation usually takes place at the level of polypeptide chain initiation. A large body of evidence indicates that the essential polypeptide chain initiation factor eIF2 is a frequent target for regulation, and that its activity is often rate-limiting for protein synthesis. The phosphorylation of the smallest (α) subunit of eIF2 is a widely used mechanism of translational control in many organisms, and there are numerous physiologically important situations where eIF2α kinases are activated or inhibited. This chapter provides a review of our knowledge concerning the mechanisms by which eIF2 is controlled by reversible protein phosphorylation.