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

Bushell, M. , Wood, W., Carpenter, G., Pain, V. M., Morley, S. J. and Clemens, M. J. (2001) 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. Journal of Biological Chemistry, 276(26), pp. 23922-23928. (doi: 10.1074/jbc.M100384200) (PMID:11274152)

Abstract

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 proteinin 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Bushell, M., Wood, W., Carpenter, G., Pain, V. M., Morley, S. J., and Clemens, M. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Biological Chemistry
• Publisher: American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258
• ISSN (Online): 1083-351X