Translational regulation in cell stress and apoptosis. Roles of the eIF4E binding proteins.
Several mechanisms have been identified by which protein synthesis may be regulated during the response of mammalian cells to physiological stresses and conditions that induce apoptotic cell death (reviewed in Clemens et al., Cell Death and Differentiation 7, 603-615, 2000). Recent developments allow us to up-date this analysis and in this article I concentrate on one particular aspect of this regulation that has not previously been reviewed in depth in relation to apoptosis, viz. the control of the initiation of protein synthesis by eukaryotic initiation factor eIF4E and the eIF4E binding proteins (4E-BPs). Changes in the state of phosphorylation of the 4E-BPs and in the extent of their association with eIF4E occur at an early stage in the response of cells to apoptotic inducers. The review discusses the mechanisms by which these events are regulated and the significance of the changes for the control of protein synthesis, cell proliferation and cell survival.
Clemens
M J
MJ
Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. M.Clemens@sghms.ac.uk
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D006801:Humans; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C104151:EIF4EBP2 protein, human; D004791:Enzyme Inhibitors; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases