Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein

Batool, Asiya; Aashaq, Sabreena; Andrabi, Khurshid Iqbal

doi:10.1002/jcb.28851

Cited by 37 publications

(25 citation statements)

References 110 publications

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“…In its active non-phosphorylated form, 4EBP2 binds to the initiation factor eIF4E through structural mimicry of eiF4G thereby preventing the binding of eIF4E to eIF4G and subsequently hindering capdependent translation [63][64][65][66]. When phosphorylated by mTOR, the 4EBP2-eIF4E complex dissociates allowing eIF4E to bind eIF4g and the 5′ m7G mRNA cap (reviewed in [67]). Moreover, the decrease in protein synthesis by sleep deprivation appears specific to cap-dependent translation as a second path to translation from mTOR through S6Kinase appears unchanged [22].…”

Section: Multiple Levels Of Gene Regulation By Acute Sleep Deprivationmentioning

confidence: 99%

Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq

et al. 2020

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Sleep deprivation is a global health problem adversely affecting health as well as causing decrements in learning and performance. Sleep deprivation induces significant changes in gene transcription in many brain regions, with the hippocampus particularly susceptible to acute sleep deprivation. However, less is known about the impacts of sleep deprivation on post-transcriptional gene regulation. To identify the effects of sleep deprivation on the translatome, we took advantage of the RiboTag mouse line to express HA-labeled Rpl22 in CaMKIIα neurons to selectively isolate and sequence mRNA transcripts associated with ribosomes in excitatory neurons. We found 198 differentially expressed genes in the ribosome-associated mRNA subset after sleep deprivation. In comparison with previously published data on gene expression in the hippocampus after sleep deprivation, we found that the subset of genes affected by sleep deprivation was considerably different in the translatome compared with the transcriptome, with only 49 genes regulated similarly. Interestingly, we found 478 genes differentially regulated by sleep deprivation in the transcriptome that were not significantly regulated in the translatome of excitatory neurons. Conversely, there were 149 genes differentially regulated by sleep deprivation in the translatome but not in the whole transcriptome. Pathway analysis revealed differences in the biological functions of genes exclusively regulated in the transcriptome or translatome, with protein deacetylase activity and small GTPase binding regulated in the transcriptome and unfolded protein binding, kinase inhibitor activity, neurotransmitter receptors and circadian rhythms regulated in the translatome. These results indicate that sleep deprivation induces significant changes affecting the pool of actively translated mRNAs.

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Section: Multiple Levels Of Gene Regulation By Acute Sleep Deprivationmentioning

confidence: 99%

Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq

et al. 2020

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“…To verify the selectivity of the identified most potent cN-IIIB inhibitors ( 5 , 5a , 5 d, and 5g ), we investigated them in the context of two other known proteins capable of recognizing m 7 GMP, eukaryotic translation initiation factor 4E (eIF4E) [ 23 , 24 ] and cN-IIIA. To assess the affinity of cN-IIIB inhibitors towards eIF4E, we applied a competition binding assay based on a pyrene-labelled fluorescent probe [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Substrate-Based Design of Cytosolic Nucleotidase IIIB Inhibitors and Structural Insights into Inhibition Mechanism

et al. 2022

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Cytosolic nucleotidases (cNs) catalyze dephosphorylation of nucleoside 5’-monophosphates and thereby contribute to the regulation of nucleotide levels in cells. cNs have also been shown to dephosphorylate several therapeutically relevant nucleotide analogues. cN-IIIB has shown in vitro a distinctive activity towards 7-mehtylguanosine monophosphate (m7GMP), which is one key metabolites of mRNA cap. Consequently, it has been proposed that cN-IIIB participates in mRNA cap turnover and prevents undesired accumulation and salvage of m7GMP. Here, we sought to develop molecular tools enabling more advanced studies on the cellular role of cN-IIIB. To that end, we performed substrate and inhibitor property profiling using a library of 41 substrate analogs. The most potent hit compounds (identified among m7GMP analogs) were used as a starting point for structure–activity relationship studies. As a result, we identified several 7-benzylguanosine 5’-monophosphate (Bn7GMP) derivatives as potent, unhydrolyzable cN-IIIB inhibitors. The mechanism of inhibition was elucidated using X-ray crystallography and molecular docking. Finally, we showed that compounds that potently inhibit recombinant cN-IIIB have the ability to inhibit m7GMP decay in cell lysates.

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“…Therefore, to create a sensor that undergoes controlled aggregation, we designed a two component AuNPs assay that relies on the use of two types of AuNP conjugate, both capable of interacting with eIF4E protein at two separate binding sites (Fig. 5 A) 42 . To that end, we used the 1:1 optimized m 7 G-cap-TL-AuNPs (above) and synthetized peptide-modified AuNPs that target the 4E-BP1/eIF4G binding site in eIF4E 30 .…”

Section: Resultsmentioning

confidence: 99%

Nucleotide-decorated AuNPs as probes for nucleotide-binding proteins

Perzanowska

Majewski

Strenkowska

et al. 2021

Sci Rep

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Gold nanoparticles (AuNPs) decorated with biologically relevant molecules have variety of applications in optical sensing of bioanalytes. Coating AuNPs with small nucleotides produces particles with high stability in water, but functionality-compatible strategies are needed to uncover the full potential of this type of conjugates. Here, we demonstrate that lipoic acid-modified dinucleotides can be used to modify AuNPs surfaces in a controllable manner to produce conjugates that are stable in aqueous buffers and biological mixtures and capable of interacting with nucleotide-binding proteins. Using this strategy we obtained AuNPs decorated with 7-methylguanosine mRNA 5’ cap analogs and showed that they bind cap-specific protein, eIF4E. AuNPs decorated with non-functional dinucleotides also interacted with eIF4E, albeit with lower affinity, suggesting that eIF4E binding to cap-decorated AuNPs is partially mediated by unspecific ionic interactions. This issue was overcome by applying lipoic-acid-Tris conjugate as a charge-neutral diluting molecule. Tris-Lipo-diluted cap-AuNPs conjugates interacted with eIF4E in fully specific manner, enabling design of functional tools. To demonstrate the potential of these conjugates in protein sensing, we designed a two-component eIF4E sensing system consisting of cap-AuNP and 4E-BP1-AuNP conjugates, wherein 4E-BP1 is a short peptide derived from 4E-BP protein that specifically binds eIF4E at a site different to that of the 5’ cap. This system facilitated controlled aggregation, in which eIF4E plays the role of the agent that crosslinks two types of AuNP, thereby inducing a naked-eye visible absorbance redshift. The reported AuNPs-nucleotide conjugation method based on lipoic acid affinity for gold, can be harnessed to obtain other types of nucleotide-functionalized AuNPs, thereby paving the way to studying other nucleotide-binding proteins.

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Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein

Cited by 37 publications

References 110 publications

Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq

Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq

Substrate-Based Design of Cytosolic Nucleotidase IIIB Inhibitors and Structural Insights into Inhibition Mechanism

Nucleotide-decorated AuNPs as probes for nucleotide-binding proteins

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