Eukaryotic initiation factor (eIF) 4E binds to the 5′-cap structure of eukaryotic mRNA and has a central role in the control of cell proliferation. We have shown previously that the stimulation of cultured Xenopus kidney cells with serum resulted in the activation of protein synthesis, enhanced phosphorylation of eIF4E and increased binding of the adapter protein, eIF4G, and poly(A)-binding protein (PABP) to eIF4E to form the functional initiation factor complex, eIF4F/PABP. We now show that cellular stresses such as arsenite, anisomycin and heat shock also result in increased phosphorylation of eIF4E, eIF4F complex formation and the association of PABP with eIF4G, in conditions under which the rate of protein synthesis is severely inhibited. In contrast with reported effects on mammalian cells, the stress-induced increase in eIF4F complex formation occurs in the absence of changes in the association of eIF4E with its binding proteins 4E-BP1 or 4E-BP2. The stress-induced changes in eIF4E phosphorylation were totally abrogated by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and were partly inhibited by the phosphoinositide 3-kinase inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. However, eIF4E phosphorylation was unaffected by extracellular signal-regulated protein kinase (MAP kinase) inhibitor PD98059. These results indicate that cellular stresses activate multiple signalling pathways that converge at the level of eIF4F complex formation to influence the interactions between eIF4E, eIF4G and PABP.
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Research Article|
September 05 1999
Cellular stress in Xenopus kidney cells enhances the phosphorylation of eukaryotic translation initiation factor (eIF)4E and the association of eIF4F with poly(A)-binding protein
Christopher S. FRASER;
Christopher S. FRASER
1Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QG, U.K.
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Virginia M. PAIN;
Virginia M. PAIN
1Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QG, U.K.
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Simon J. MORLEY
Simon J. MORLEY
1
1Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QG, U.K.
1To whom correspondence should be addressed (s.j.morleyxy@sussex.ac.uk).
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Publisher: Portland Press Ltd
Received:
April 13 1999
Revision Received:
June 01 1999
Accepted:
July 06 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 342 (3): 519–526.
Article history
Received:
April 13 1999
Revision Received:
June 01 1999
Accepted:
July 06 1999
Citation
Christopher S. FRASER, Virginia M. PAIN, Simon J. MORLEY; Cellular stress in Xenopus kidney cells enhances the phosphorylation of eukaryotic translation initiation factor (eIF)4E and the association of eIF4F with poly(A)-binding protein. Biochem J 15 September 1999; 342 (3): 519–526. doi: https://doi.org/10.1042/bj3420519
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