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Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1)

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)1374-1379
Number of pages6
JournalCurrent Biology
Volume11
Issue number17
DatePublished - 4 Sep 2001

Abstract

A fundamental control point in the regulation of the initiation of protein synthesis is the formation of the eukaryotic initiation factor 4F (elF-4F) complex. The formation of this complex depends upon the availability of the mRNA cap binding protein, elF-4E, which is sequestered away from the translational machinery by the tight association of elF-4E binding proteins (4E-BPs). Phosphorylation of 4E-BP1 is critical in causing its dissociation from elF-4E, leaving 4E available to form translationally active elF-4F complexes, switching on mRNA translation. In this report, we provide the first evidence that the phosphorylation of 4E-BP1 increases during mitosis and identify Ser-65 and Thr-70 as phosphorylated sites. Phosphorylation of Thr-70 has been implicated in the regulation of 4E-BP1 function, but the kinase phosphorylating this site was unknown. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4E-BP1 at Thr-70 and that phosphorylation of this site is permissive for Ser-65 phosphorylation. Crucially, the increased phosphorylation of 4E-BP1 during mitosis results in its complete dissociation from elF-4E.

    Research areas

  • FACTOR 4E-BINDING PROTEIN-1, CDC2 KINASE, PHAS-I, INITIATION, MITOSIS, INSULIN, REGULATOR, RAPAMYCIN, SITES

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