title: Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells.
abstract: The rate of protein synthesis is rapidly down-regulated in mammalian cells following the induction of apoptosis. Inhibition occurs at the level of polypeptide chain initiation and is accompanied by the phosphorylation of the alpha subunit of initiation factor eIF2 and the caspase-dependent cleavage of initiation factors eIF4G, eIF4B, eIF2alpha and the p35 subunit of eIF3. Proteolytic cleavage of these proteins yields characteristic products which may exert regulatory effects on the translational machinery. Inhibition of caspase activity protects protein synthesis from long-term inhibition in cells treated with some, but not all, inducers of apoptosis. This review describes the initiation factor modifications and the possible signalling pathways by which translation may be regulated during apoptosis. We discuss the significance of the initiation factor cleavages and other changes for protein synthesis, and the implications of these events for our understanding of the cellular changes associated with apoptosis.
authors.affiliation: Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK. M.Clemens@sghms.ac.uk
authors.forename: M J
authors.initials: MJ
authors.lastname: Clemens
authors.forename: M
authors.initials: M
authors.lastname: Bushell
authors.forename: I W
authors.initials: IW
authors.lastname: Jeffrey
authors.forename: V M
authors.initials: VM
authors.lastname: Pain
authors.forename: S J
authors.initials: SJ
authors.lastname: Morley
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D006801:Humans; D010452:Peptide Biosynthesis; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D010448:Peptide Initiation Factors; D011494:Protein Kinases; D020169:Caspases