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The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila

Nature Cell Biology volume 3, pages 596–601 (2001)Cite this article

Abstract

The initiation factor 4E for eukaryotic translation (eIF4E) binds the messenger RNA 5′-cap structure and is important in the regulation of protein synthesis1. Mammalian eIF4E activity is inhibited when the initiation factor binds to the translational repressors, the 4E-binding proteins (4E-BPS)1. Here we show that the Drosophila melanogaster 4E-BP (d4E-BP) is a downstream target of the phosphatidylinositol-3-OH kinase (PI(3)K) signal-transduction cascade, which affects the interaction of d4E-BP with eIF4E. Ectopic expression of a highly active d4E-BP mutant in wing-imaginal discs causes a reduction of wing size, brought about by a decrease in cell size and number. A marked reduction in cell size was also observed in post-mitotic cells. Expression of d4E-BP in the eye and wing together with PI(3)K or dAkt1, the serine/threonine kinase downstream of PI(3)K, resulted in suppression of the growth phenotype elicited by these kinases. Our results support a role for d4E-BP as an effector of cell growth.

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Figure 1: Sequence of d4E-BP, interaction between deIF4E and d4E-BP, and signalling to d4E-BP.
Figure 2: Effect of ectopic expression of d4E-BP(LL) in wing tissues.
Figure 3: Effect of ectopic expression of d4E-BP(LL) in post-mitotic tissues.
Figure 4: PI(3)K/Akt signalling is antagonized by d4E-BP expression.

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Acknowledgements

We thank B. Raught, A.-C. Gingras and F. Poulin for critically reading the manuscript; C. Lister and K. McDonald for technical assistance; A. Nakamura, T.P. Neufeld and S. Styhler for discussions; B.A. Edgar and S.J. Leevers for the gift of flies. This work was supported by a grant from the Canadian Institute of Health Research (to P.L. and N.S), a grant from the Howard Hughes Medical Institute (to N.S.), a graduate fellowship from the Cancer Research Society (to M.M.), a graduate fellowship from the National Science and Engineering Research Council of Canada (to P.E.D.L.) and a J.W. McConnell McGill major fellowship.

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Author notes

  1. Javier Verdú and Pascal E.D. Lachance: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biochemistry and McGill Cancer Center, McGill University, 3655 Promenade Sir-William-Osler, Montréal, H3G 1Y6, Québec, Canada

    Mathieu Miron, Javier Verdú & Nahum Sonenberg

  2. Howard Hughes Medical Institute and Department of Medicine, 415 Curie Boulevard

    Morris J. Birnbaum

  3. Clinical Research Building, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Morris J. Birnbaum

  4. Department of Biology, McGill University, 1205 Avenue Dr Penfield, Montréal, H3A 1B1, Québec, Canada

    Pascal E.D. Lachance & Paul F. Lasko

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  1. Mathieu Miron
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  2. Javier Verdú
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  3. Pascal E.D. Lachance
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  4. Morris J. Birnbaum
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  5. Paul F. Lasko
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  6. Nahum Sonenberg
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Correspondence to Nahum Sonenberg.

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Miron, M., Verdú, J., Lachance, P. et al. The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila. Nat Cell Biol 3, 596–601 (2001). https://doi.org/10.1038/35078571

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