Faculty Opinions recommendation of Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

2005 ◽  
Author(s):  
Lynne Maquat
Keyword(s):  
Translation Initiation ◽  
Binding Protein ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

scholarly journals PLK1 regulates spindle association of phosphorylated eukaryotic translation initiation factor 4E-binding protein and spindle function in mouse oocytes

2017 ◽  
Vol 313 (5) ◽  
pp. C501-C515 ◽  
Author(s):  
Ashley L. Severance ◽  
Keith E. Latham
Keyword(s):  
Translation Initiation ◽  
Binding Protein ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Spindle Formation ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Chromosome Congression ◽  
Eukaryotic Translation Initiation ◽  
Meiotic Spindles

Oocyte meiotic spindles are associated with spindle-enriched mRNAs, phosphorylated ribosome protein S6, and phosphorylated variants of the key translational regulator, eukaryotic translation initiation factor 4E-binding protein 1 (eIF4E-BP1), consistent with translational control of localized mRNAs by eIF4E-BP1 in facilitating spindle formation and stability. Using specific kinase inhibitors, we determined which kinases regulate phosphorylation status of eIF4E-BP1 associated with meiotic spindles in mouse oocytes and effects of kinase inhibition on chromosome congression and spindle formation. Neither ataxia telangiectasia-mutated kinase nor mechanistic target of rapamycin inhibition significantly affected phosphorylation status of spindle-associated eIF4E-BP1 at the phosphorylation sites examined. Spindle-associated phospho-eIF4E-BP1, spindle formation, and chromosome congression were strongly disrupted by polo-like kinase I (PLK1) inhibition at both metaphase I (MI) and MII. In addition, direct inhibition of eIF4E-BP1 via 4EGI led to spindle defects at MI, indicating a direct role for eIF4E-BP1 phosphorylation in meiotic spindle formation. PLK1 also regulated microtubule dynamics throughout the ooplasm, indicating likely coordination between spindle dynamics and broader ooplasm cytoskeletal dynamics. Because diverse upstream signaling pathways converge on PLK1, these results implicate PLK1 as a major regulatory nexus coupling endogenous and exogenous signals via eIF4E-BP1 to the regulation of spindle formation and stability.

scholarly journals Identification in the Ancient Protist Giardia lamblia of Two Eukaryotic Translation Initiation Factor 4E Homologues with Distinctive Functions

2005 ◽  
Vol 4 (5) ◽  
pp. 948-959 ◽  
Author(s):  
Lei Li ◽  
Ching C. Wang
Keyword(s):  
Translation Initiation ◽  
Giardia Lamblia ◽  
Binding Protein ◽  
Ribosomal Subunit ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Affinity Column ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

ABSTRACT Eukaryotic translation initiation factor 4E (eIF4E) binds to the m7GTP of capped mRNAs and is an essential component of the translational machinery that recruits the 40S small ribosomal subunit. We describe here the identification and characterization of two eIF4E homologues in an ancient protist, Giardia lamblia. Using m7GTP-Sepharose affinity column chromatography, a specific binding protein was isolated and identified as Giardia eIF4E2. The other homologue, Giardia eIF4E1, bound only to the m2,2,7GpppN structure. Although neither homologue can rescue the function of yeast eIF4E, a knockdown of eIF4E2 mRNA in Giardia by a virus-based antisense ribozyme decreased translation, which was shown to use m7GpppN-capped mRNA as a template. Thus, eIF4E2 is likely the cap-binding protein in a translation initiation complex. The same knockdown approach indicated that eIF4E1 is not required for translation in Giardia. Immunofluorescence assays showed wide distribution of both homologues in the cytoplasm. But eIF4E1 was also found concentrated and colocalized with the m2,2,7GpppN cap, 16S-like rRNA, and fibrillarin in the nucleolus-like structure in the nucleus. eIF4E1 depletion from Giardia did not affect mRNA splicing, but the protein was bound to Giardia small nuclear RNAs D and H known to have an m2,2,7GpppN cap, thus suggesting a novel function not yet observed among other eIF4Es in eukaryotes.

scholarly journals Eukaryotic Translation Initiation Factor 4F Architectural Alterations Accompany Translation Initiation Factor Redistribution in Poxvirus-Infected Cells

2008 ◽  
Vol 28 (8) ◽  
pp. 2648-2658 ◽  
Author(s):  
Derek Walsh ◽  
Carolina Arias ◽  
Cesar Perez ◽  
David Halladin ◽  
Martin Escandon ◽  
...  
Keyword(s):  
Viral Replication ◽  
Translation Initiation ◽  
Binding Protein ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Translational Repressor ◽  
Eukaryotic Translation Initiation ◽  
Control Translation

ABSTRACT Despite their self-sufficient ability to generate capped mRNAs from cytosolic DNA genomes, poxviruses must commandeer the critical eukaryotic translation initiation factor 4F (eIF4F) to recruit ribosomes. While eIF4F integrates signals to control translation, precisely how poxviruses manipulate the multisubunit eIF4F, composed of the cap-binding eIF4E and the RNA helicase eIF4A assembled onto an eIF4G platform, remains obscure. Here, we establish that the poxvirus infection of normal, primary human cells destroys the translational repressor eIF4E binding protein (4E-BP) and promotes eIF4E assembly into an active eIF4F complex bound to the cellular polyadenylate-binding protein (PABP). Stimulation of the eIF4G-associated kinase Mnk1 promotes eIF4E phosphorylation and enhances viral replication and protein synthesis. Remarkably, these eIF4F architectural alterations are accompanied by the concentration of eIF4E and eIF4G within cytosolic viral replication compartments surrounded by PABP. This demonstrates that poxvirus infection redistributes, assembles, and modifies core and associated components of eIF4F and concentrates them within discrete subcellular compartments. Furthermore, it suggests that the subcellular distribution of eIF4F components may potentiate the complex assembly.

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