| Title | Disruption of the interaction of mammalian protein synthesis eukaryotic initiation factor 4B with the poly(A)-binding protein by caspase- and viral protease-mediated cleavages. | ||
| Author | Bushell, M; Wood, W; Carpenter, G; Pain, V M; Morley, S J; Clemens, M J | ||
| Journal | J Biol Chem | Publication Year/Month | 2001-Jun |
| PMID | 11274152 | PMCID | -N/A- |
| Affiliation | 1.Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom. | ||
Eukaryotic initiation factor (eIF) 4B interacts with several components of the initiation pathway and is targeted for cleavage during apoptosis. In a cell-free system, cleavage of eIF4B by caspase-3 coincides with a general inhibition of protein synthetic activity. Affinity chromatography demonstrates that mammalian eIF4B interacts with the poly(A)-binding protein and that a region consisting of the N-terminal 80 amino acids of eIF4B is both necessary and sufficient for such binding. This interaction is lost when eIF4B is cleaved by caspase-3, which removes the N-terminal 45 amino acids. Similarly, the association of eIF4B with the poly(A)-binding protein in vivo is reduced when cells are induced to undergo apoptosis. Cleavage of the poly(A)-binding protein itself, using human rhinovirus 3C protease, also eliminates the interaction with eIF4B. Thus, disruption of the association between mammalian eIF4B and the poly(A)-binding protein can occur during both apoptosis and picornaviral infection and is likely to contribute to the inhibition of translation observed under these conditions.