tailieunhanh - Báo cáo Y học: Does phosphorylation of the cap-binding protein eIF4E play a role in translation initiation?

Eukaryotic initiation factor 4E (eIF4E) plays an important role inmRNA translation by binding the 5¢-cap structure of themRNAand facilitating the recruitment to themRNAof other translation factors and the 40S ribosomal subunit. eIF4E can interact either with the scaffold protein eIF4Gor withrepressor proteins termed eIF4E-binding proteins (4E-BPs). Highlevels of expression can disrupt cellular growthcontrol and are associated withhuman cancers. | Eur. J. Biochem. 269 5350-5359 2002 FEBS 2002 doi MINIREVIEW Does phosphorylation of the cap-binding protein eIF4E play a role in translation initiation Gert C. Scheper and Christopher G. Proud Division of Molecular Physiology School of Life Sciences University of Dundee MSI WTB Complex Dow Street UK Eukaryotic initiation factor 4E eIF4E plays an important role in mRNA translation by binding the 5 -cap structure of the mRNA and facilitating the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. eIF4E can interact either with the scaffold protein eIF4G or with repsessor proieins termed eIF4E-binnigg proieins 4E-BPs . High levt ls of exp is ssim cm disrppt eellular growthcontrol and are associated withhuman cancers. A fraction of the cellular eIF4E is found in the nucleus where it may play a role in the transport of certain mRNAs to the cytoplasm. eIF4E undergoes regulated phosphorylation at Ser209 by members of the Mnk group of kinases which are actieated by multiple MAP kinases hence Mnk MAP-kinase signal integrating kinase . The functional significance of its phosphorylation has been the subject of considerable interest. Recent genetic studies in Drosophila point to a key role for phosphorylation of eIF4E in growth and eiability. Initial structural data suggested that phosphorylation of Ser209 might allow formation of a salt bridge with a basic residue Lys159 that would clamp eIF4E onto the mRNA and increase its affinity for ligand. However more recent structural data place Ser209 too far away from Lys159 to form suchan interaction and biophysical studies indicate that phosphorylation actually decreases the affinity of eIF4E for cap or capped RNA. The implications of these studies are discussed in the light of other in vitro and in vivo ineesti-gations designed to address the role of eIF4E phosphorylation in mRNA translation or its control. Keywords eIF4E phosphorylation Mnk mRNA initiation complee.

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