The University of Southampton
University of Southampton Institutional Repository

Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors

Patel, J., McLeod, L.E., Vries, R.G.J., Flynn, A., Wang, X.M. and Proud, C.G. (2002) Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors European Journal of Biochemistry, 269, (12), pp. 3076-3085. (doi:10.1046/j.1432-1033.2002.02992.x).

Record type: Article


We have examined the effects of widely used stress-inducing agents on protein synthesis and on regulatory components of the translational machinery. The three stresses chosen, arsenite, hydrogen peroxide and sorbitol, exert their effects in quite different ways. Nonetheless, all three rapidly (? 30 min) caused a profound inhibition of protein synthesis. In each case this was accompanied by dephosphorylation of the eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and increased binding of this repressor protein to eIF4E. Binding of 4E-BP1 to eIF4E correlated with loss of eIF4F complexes. Sorbitol and hydrogen peroxide each caused inhibition of the 70-kDa ribosomal protein S6 kinase, while arsenite activated it. The effects of stresses on the phosphorylation of eukaryotic elongation factor 2 also differed: oxidative stress elicited a marked increase in eEF2 phosphorylation, which is expected to contribute to inhibition of translation, while the other stresses did not have this effect. Although all three proteins (4E-BP1, p70 S6 kinase and eEF2) can be regulated through the mammalian target of rapamycin (mTOR), our data imply that stresses do not interfere with mTOR function but act in different ways on these three proteins. All three stresses activate the p38 MAP kinase pathway but we were able to exclude a role for this in their effects on 4E-BP1. Our data reveal that these stress-inducing agents, which are widely used to study stress-signalling in mammalian cells, exert multiple and complex inhibitory effects on the translational machinery.

Full text not available from this repository.

More information

Published date: 1 June 2002


Local EPrints ID: 55877
ISSN: 0014-2956
PURE UUID: 9efcdc21-07c1-4932-8b79-f403097f1d48

Catalogue record

Date deposited: 06 Aug 2008
Last modified: 17 Jul 2017 14:31

Export record



Author: J. Patel
Author: L.E. McLeod
Author: R.G.J. Vries
Author: A. Flynn
Author: X.M. Wang
Author: C.G. Proud

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.