Suppression of cap-dependent translation in mitosis.

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Pyronnet S,Dostie J,Sonenberg N

doi

10.1101/gad.889201

subject

Has Abstract

pub_date

2001-08-15 00:00:00

pages

2083-93

issue

16

eissn

0890-9369

issn

1549-5477

journal_volume

15

pub_type

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