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Echinobase
ECB-ART-41090
PLoS One 2009 Jan 01;43:e5070. doi: 10.1371/journal.pone.0005070.
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A variant mimicking hyperphosphorylated 4E-BP inhibits protein synthesis in a sea urchin cell-free, cap-dependent translation system.

Oulhen N , Boulben S , Bidinosti M , Morales J , Cormier P , Cosson B .


Abstract
BACKGROUND: 4E-BP is a translational inhibitor that binds to eIF4E to repress cap-dependent translation initiation. This critical protein:protein interaction is regulated by the phosphorylation of 4E-BP. Hypophosphorylated 4E-BP binds to eIF4E and inhibits cap-dependent translation, whereas hyperphosphorylated forms do not. While three 4E-BP proteins exist in mammals, only one gene encoding for 4E-BP is present in the sea urchin genome. The protein product has a highly conserved core domain containing the eIF4E-binding domain motif (YxxxxLPhi) and four of the regulatory phosphorylation sites. METHODOLOGY/PRINCIPAL FINDINGS: Using a sea urchin cell-free cap-dependent translation system prepared from fertilized eggs, we provide the first direct evidence that the sea urchin 4E-BP inhibits cap-dependent translation. We show here that a sea urchin 4E-BP variant, mimicking phosphorylation on four core residues required to abrogate binding to eIF4E, surprisingly maintains physical association to eIF4E and inhibits protein synthesis. CONCLUSIONS/SIGNIFICANCE: Here, we examine the involvement of the evolutionarily conserved core domain and phosphorylation sites of sea urchin 4E-BP in the regulation of eIF4E-binding. These studies primarily demonstrate the conserved activity of the 4E-BP translational repressor and the importance of the eIF4E-binding domain in sea urchin. We also show that a variant mimicking hyperphosphorylation of the four regulatory phosphorylation sites common to sea urchin and human 4E-BP is not sufficient for release from eIF4E and translation promotion. Therefore, our results suggest that there are additional mechanisms to that of phosphorylation at the four critical sites of 4E-BP that are required to disrupt binding to eIF4E.

PubMed ID: 19333389
PMC ID: PMC2659438
Article link: PLoS One


Species referenced: Echinodermata
Genes referenced: 4e-bp LOC100887844 LOC115919910 LOC587333 LOC594261 LOC594349


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References [+] :
Brandhorst, Two-dimensional gel patterns of protein synthesis before and after fertilization of sea urchin eggs. 2002, Pubmed, Echinobase