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

Curr Biol. 2001 Sep 4;11(17):1374-9. doi: 10.1016/s0960-9822(01)00422-5.

Abstract

A fundamental control point in the regulation of the initiation of protein synthesis is the formation of the eukaryotic initiation factor 4F (eIF-4F) complex. The formation of this complex depends upon the availability of the mRNA cap binding protein, eIF-4E, which is sequestered away from the translational machinery by the tight association of eIF-4E binding proteins (4E-BPs). Phosphorylation of 4E-BP1 is critical in causing its dissociation from eIF-4E, leaving 4E available to form translationally active eIF-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 eIF-4E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • CDC2 Protein Kinase / metabolism
  • Carrier Proteins / metabolism*
  • Cell Cycle
  • Eukaryotic Initiation Factor-4E
  • HeLa Cells
  • Humans
  • Peptide Initiation Factors / metabolism*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Biosynthesis*
  • Repressor Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • EIF4EBP1 protein, human
  • Eukaryotic Initiation Factor-4E
  • Peptide Initiation Factors
  • Phosphoproteins
  • Repressor Proteins
  • CDC2 Protein Kinase