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