Disease relevance of EIF4B

• Cleavage of the poly(A)-binding protein itself, using human rhinovirus 3C protease, also eliminates the interaction with eIF4B [1].
• These data indicate that eIF4B and 4H stimulate the nuclease activity of vhs, and they provide evidence that additional mammalian factors are required for targeting to the EMCV IRES [2].
• Herpes simplex virus virion host shutoff protein is stimulated by translation initiation factors eIF4B and eIF4H [2].
• Here we show that both the 28-kDa subunit of eIF-4B and the 26-kDa subunit of eIF-4F cross-link to the 5' terminus of capped and oxidized satellite tobacco necrosis virus RNA in the absence of ATP and that the cross-linking of both polypeptides is inhibited by m7GDP [3].
• These results indicate that the interaction of eIF4B with the 3" region of the poliovirus IRES may be directly involved in translation initiation [4].

High impact information on EIF4B

• Phosphorylation results in S6K1 dissociation, activation, and subsequent phosphorylation of its translational targets, including eIF4B, which is then recruited into the complex in a phosphorylation-dependent manner [5].
• The levels of initiation factors eIF-2, eIF-3, eIF-4A, and eIF-4B were quantitated by immunoblotting; all are enriched in the cytoskeletal fraction relative to the soluble fraction [6].
• Consistent with this requirement, phosphorylation of eIF4B Ser422 is abrogated in PDK1 null embryonic stem cells [7].
• The relative contribution of the RSK and S6K modules to the phosphorylation of eIF4B is growth factor-dependent, and the two phosphorylation events exhibit very different kinetics [7].
• Eukaryotic protein synthesis initiation factor 4B (eIF-4B) is an 80,000 dalton polypeptide which is essential for the binding of mRNA to ribosomes [8].

Biological context of EIF4B

• Substitution of Ser422 with Ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eIF4B function [9].
• Degenerate oligonucleotide probes were used to isolate a 3851 bp cDNA encoding eIF-4B from a human cDNA library [8].
• A highly purified preparation of eIF-4B from HeLa cells was subjected to enzymatic cleavage and amino-terminal amino acid sequence analysis [8].
• We examined the effects of deletions and point mutations on the ability of eIF-4B to bind a random RNA, to cooperate with eIF-4A in RNA binding, and to enhance the helicase activity of eIF-4A [10].
• The translation initiation factor eIF-4B contains an RNA-binding region that is distinct and independent from its ribonucleoprotein consensus sequence [10].

Anatomical context of EIF4B

• Expression of eIF-4B in COS-1 cells resulted in a general inhibition of translation, possibly due to a 50-fold eIF-4B overproduction [8].
• In a cell-free system, cleavage of eIF4B by caspase-3 coincides with a general inhibition of protein synthetic activity [1].
• A reconstituted reticulocyte translation system originally designed to be deficient in eukaryotic initiation factor 4B (eIF-4B) was used to identify a new activity required for maximal synthesis of rabbit globin [11].

Associations of EIF4B with chemical compounds

• A region rich in aspartic acid, arginine, tyrosine, and glycine, termed the DRYG domain, is sufficient for self-association of eIF4B, both in vitro and in vivo, and for interaction with the p170 subunit of eIF3 [12].
• A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3 [12].
• In addition to a conserved RNA recognition motif and a C-terminal RNA binding domain, wheat eIF4B contains a novel N-terminal RNA binding domain that requires a short, lysine-rich containing sequence [13].
• Plant eIF4B contains three RNA binding domains, one more than reported for mammalian or yeast eIF4B, and each domain exhibits a preference for purine-rich RNA [13].
• Eukaryotic initiation factor 2 (eIF2), eIF3, and eIF4F were required for initiation; eIF4B and to a lesser extent the pyrimidine tract-binding protein stimulated this process [14].

Physical interactions of EIF4B

• Affinity chromatography demonstrates that mammalian eIF4B interacts with the poly(A)-binding protein and that a region consisting of the N-terminal 80 amino acids of eIF4B is both necessary and sufficient for such binding [1].
• Several lines of evidence indicate that the 28-kDa and the 26-kDa cap binding proteins of eIF-4B and eIF-4F are antigenically distinct polypeptides [3].

Regulatory relationships of EIF4B

• Next to their well-known roles in the initiation process, eIF-2 and eIF-3 also cross-linked to the 5' cap. eIF-2 stimulated eIF-4B and -4E cross-linking, an observation that has been previously described more extensively [15].

Other interactions of EIF4B

• Similarly, the association of eIF4B with the poly(A)-binding protein in vivo is reduced when cells are induced to undergo apoptosis [1].
• Activity was strongly enhanced by the addition of RRL, eIF4H, or the related translation factor eIF4B [2].
• eIF-4B is a eukaryotic translation initiation factor that is required for the binding of ribosomes to mRNAs and the stimulation of the helicase activity of eIF-4A [10].
• In this study, we have purified the phosphorylated and hypophosphorylated isoforms of PABP from wheat to examine whether its phosphorylation state affects its binding to poly(A) RNA and its interaction with eIF4G, eIFiso4G, or eIF4B [16].
• Casein kinase I incorporates phosphate only into eIF-4B, but to a limited extent [17].

Analytical, diagnostic and therapeutic context of EIF4B

• Northern blot analysis shows that eIF4H is expressed ubiquitously in human tissues, and displays different levels of expression in given tissues relative to eIF4B [18].
• The interactions between PABP and eIF-4F, eIF-iso4F, and eIF-4B were measured in the absence of poly(A) RNA using far Western analysis and confirmed by direct fluorescence titration studies [19].
• We have determined the isoelectric states for the wheat translation initiation factors eIF-4A, eIF-4B, eIF-4F, eIF-iso4F, and eIF-2 and the poly(A)-binding protein in the seed, during germination, and following heat shock of wheat seedlings using two-dimensional gel electrophoresis and Western analysis [20].
• Resolution of 32P-labeled lysates by isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the eIF-2 alpha modification and the loss of eIF-4B variants reflected changes in phosphorylation states [21].
• Immunoprecipitation with eIF-4B antiserum revealed that the protein is identical to the initiation factor eIF-4B [22].

References