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Vol. 15, No. 16, pp. 2083-2093, August 15, 2001

RESEARCH PAPER
Suppression of cap-dependent translation in mitosis

Stéphane Pyronnet,1,2 Josée Dostie,1,3 and Nahum Sonenberg4

Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada

Cap-dependent translation is mediated by eIF4F, a protein complex composed of three subunits as follows: eIF4E, which recognizes the mRNA 5' cap structure; eIF4A, an RNA-helicase; and eIF4G, a scaffolding protein that binds eIF4E, eIF4A, and the eIF4E-kinase Mnk1 simultaneously. eIF4E is hypophosphorylated and cap-dependent translation is reduced at mitosis. Here, we show that 4E-BP1, a suppressor of eIF4E function, is also hypophosphorylated in mitosis, resulting in disruption of the eIF4F complex. Consequently, eIF4E is sequestered from the eIF4G/Mnk1 complex. These results explain the specific inhibition of cap-dependent translation in mitosis and also explain how eIF4E is rendered hypophosphorylated during mitosis. Furthermore, eIF4E interaction with eIF4GII is strongly decreased coincident with hyperphosphorylation of eIF4GII. Thus, inhibition of cap-dependent translation in mitosis results from a combination of phosphorylation modifications leading to eIF4F complex disruption.

[Key Words: Translation initiation; mitosis; cap-binding complex; internal ribosome entry site]


1 These authors contributed equally to this work.

Present addresses: 2INSERM U531, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse, France; 3Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

4 Corresponding author.


GENES & DEVELOPMENT 15:2083-2093 © 2001 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/01 $5.00

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