Changes in integrity and association of eukaryotic protein synthesis initiation factors during apoptosis

Bushell, M. , Wood, W., Clemens, M. J. and Morley, S. J. (2000) Changes in integrity and association of eukaryotic protein synthesis initiation factors during apoptosis. European Journal of Biochemistry, 267(4), pp. 1083-1091. (doi: 10.1046/j.1432-1327.2000.01101.x) (PMID:10672017)

Abstract

Induction of apoptosis results in inhibition of the rate of overall protein synthesis in a variety of cell types. We have shown previously that polypeptide chain initiation factor eIF4GI is rapidly cleaved by caspase‐3, whereas other components of the eIF4F complex are much more stable during apoptosis in BJAB and Jurkat cells. We have now extended our analysis to other factors involved in the initiation of protein synthesis and we report here that eIF4B, the p35 subunit of eIF3, and minor proportions of the α subunit of eIF2 and the eIF4E‐binding protein 4E‐BP1 are also cleaved to give rise to discrete fragments. These cleavages occur with delayed kinetics relative to that seen for eIF4GI, and eIF2β and eIF2γ levels also decrease at a relatively late stage of apoptosis. In contrast, the second form of eIF4G described recently, eIF4GII, is cleaved as rapidly as eIF4GI under the same conditions. Purified recombinant caspase‐3 is able to degrade eIF4B and eIF3(p35) in vitro, producing fragments of the same sizes as those seen in intact cells. Induction of apoptosis also results in a biphasic change in the association of 4E‐BP1 with eIF4E. Thus the progress of apoptosis is characterized by a complex programme of changes in several initiation factors, including the specific fragmentation or complete degradation of some and alterations in the association status of others. These events are likely to contribute to the inhibition of protein synthesis seen under these conditions.

• Item Type: Articles
• Additional Information: This research was supported by grants from The Wellcome Trust (grants 045619 and 056778), The Royal Society and the Cancer Prevention Research Trust. M. B. was funded by a BBSRC Industrial CASE Studentship in collaboration with Roche Discovery (Welwyn Garden City) and S. J. M. is a Senior Research Fellow of the Wellcome Trust.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Bushell, M., Wood, W., Clemens, M. J., and Morley, S. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: European Journal of Biochemistry
• Publisher: Wiley
• ISSN: 0014-2956
• ISSN (Online): 1432-1033