Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells

The rate of protein synthesis is rapidly down-regulated in mammalian cells following the induction of apoptosis, Inhibition occurs at the level of pol ypeptide chain initiation and is accompanied by the phosphorylation of the alpha subunit of initiation factor elF2 and the caspase-dependent cleavage of initiation factors elF4G, elF4B, elF2 alpha and the p35 subunit of elF3, Proteolytic cleavage of these proteins yields characteristic products whic h may exert regulatory effects on the translational machinery. Inhibition o f caspase activity protects protein synthesis from long-term inhibition in cells treated with some, but not all, inducers of apoptosis, This review de scribes the initiation factor modifications and the possible signalling pat hways by which translation may be regulated during apoptosis, We discuss th e significance of the initiation factor cleavages and other changes for pro tein synthesis, and the implications of these events for our understanding of the cellular changes associated with apoptosis.