21 Regulation of Translation Elongation and the Cotranslational Protein Targeting Pathway

The factors involved in translation elongation are subject to sophisticated control mechanisms that come into play under a wide variety of conditions. Even though translation is most frequently controlled during the initiation phase (Chapter 1) and the regulatory mechanisms impinging on the initiation steps have received considerable attention (reviewed in several chapters of this book), accumulating information points to the elongation phase as a target for controls under defined circumstances. In this chapter, we focus on recent developments in understanding the control of elongation in mammalian cells. As a special case, we also discuss cotranslational protein targeting, a cellular process involving the control of elongation on an important class of mRNAs. REGULATION OF TRANSLATION ELONGATION The mechanism of peptide-chain elongation and the functions of translation elongation factors are described in Chapters 2 and 3. In addition, detailed aspects of the structure and function of eukaryotic elongation factor 2 (eEF2) are the subject of a recent informative review (Jorgensen et al. 2006). eEF2 is a phosphoprotein in mammalian cells, and most of the recent advances relate to the regulation of eEF2 and its cognate kinase, eEF2 kinase. eEF1A and eEF1B also are phosphoproteins and have been discussed in earlier reviews on this subject (Proud 2000; Traugh 2001; Browne and Proud 2002; Le Sourd et al. 2006). Significance of eEF2 Phosphorylation for the Control of Protein Synthesis Under a diverse range of conditions, the phosphorylation state of eEF2 changes in directions consistent with its having a role in regulating protein synthesis; i.e.,...