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

Clemens, M.J., Bushell, M. , Jeffrey, I.W., Pain, V.M. and Morley, S.J. (2000) Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells. Cell Death and Differentiation, 7(7), pp. 603-615. (doi:10.1038/sj.cdd.4400695) (PMID:10889505)

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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 α subunit of initiation factor eIF2 and the caspase-dependent cleavage of initiation factors eIF4G, eIF4B, eIF2α 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.

Item Type:Articles
Additional Information:Research in our laboratories is supported by grants from the Wellcome Trust (grants 040800, 045619 and 056778), the Leukaemia Research Fund, the Cancer Prevention Research Trust and Glaxo-Wellcome. SJ Morley is a Senior Research Fellow of the Wellcome Trust.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Clemens, M.J., Bushell, M., Jeffrey, I.W., Pain, V.M., and Morley, S.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Death and Differentiation
Publisher:Springer Nature
ISSN:1350-9047
ISSN (Online):1476-5403

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