tailieunhanh - Báo cáo Y học: Regulation of peptide-chain elongation in mammalian cells

The elongation phase of mRNA translation is the stage at which the polypeptide is assembled and requires a substantial amount of metabolic energy. Translation elongation in mammals requires a set of nonribosomal proteins called eukaryotic elongation actors or eEFs. Several of these proteins are subject to phosphorylation in mammalian cells, including the factors eEF1A and eEF1B that are involved in recruitment of amino acyl-tRNAs to the ribosome. | Eur. J. Biochem. 269 5360-5368 2002 FEBS 2002 doi MINIREVIEW Regulation of peptide-chain elongation in mammalian cells Gareth J. Browne and Christopher G. Proud Division of Molecular Physiology School of Life Sciences University of Dundee MSI WTB Complex Dundee UK The elongation phase of mRNA translation is the stage at which the polypeptide is assembled and requires a substantial amount of metabolic energy. Translation elongation in mammals requires a set of nonribosomal proteins called eukaryotic elongation actors or eEFs. Several of these proteins are subject to phosphorylation in mammalian cells including the factors eEF1A and eEF1B that are involved in recruitment of amino acyl-tRNAs to the ribosome. eEF2 which mediates ribosomal translocation is also phosphorylated and this inhibits its activity. The kinase acting on eEF2 is an unusual and specific one whose activity is dependent on calcium ions and calmodulin. Recent workhas shown that the activity of eEF2 kinase is regulated by MAP kinase signalling and by the nutrient-sensitive mTOR signalling pathway which serve to activate eEF2 in response to mitogenic or hormonal stimuli. Conversely eEF2 is inactivated by phosphorylation in response to stimuli that increase energy demand or reduce its supply. This likely serves to slow down protein synthesis and thus conserve energy under such circumstances. Keywords translation elongation factor mTOR rapamy-cin eEF1 eEF2. INTRODUCTION Recent years have seen major advances in our understanding of the control of mRNA translation both via regulation of proteins that bind to specific mRNAs and modulate their translation and through control of the activities of components of the core translational machinery. In the latter area much attention has been directed at understanding the regulation of the initiation process. As described in the accompanying articles 1 2 and elsewhere 3-6 multiple mechanisms operate to modulate translation .