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

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 i nhibition of protein synthetic activity. Affinity chromatography demonstrat es 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 nece ssary and sufficient for such binding. This interaction is lost when eIF4B is cleaved by caspase-3, which removes the N-terminal 45 amino acids. Simil arly, the association of eIF4B with the poly(a)binding protein in vivo is r educed 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 ma mmalian eIF4B and the poly(A)-binding protein can occur during both apoptos is and picornaviral infection and is Likely to contribute to the inhibition of translation observed under these conditions.