Mitosis-related phosphorylation of the eukaryotic translation suppressor 4E-BP1 and its interaction with eukaryotic translation initiation factor 4E (eIF4E)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA544328 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Eukaryotic translation initiation factor 4E (eIF4E)–binding protein 1 (4E-BP1) inhibits cap-dependent translation in eukaryotes by competing with eIF4G for an interaction with eIF4E. Phos-phorylation at Ser-83 of 4E-BP1 occurs during mitosis through the activity of cyclin-dependent kinase 1 (CDK1)/cyclin B rather than through canonical mTOR kinase activity. Here, we investi-gated the interaction of eIF4E with 4E-BP1 or eIF4G during interphase and mitosis. We observed that 4E-BP1 and eIF4G bind eIF4E at similar levels during interphase and mitosis. The most highly phosphorylated mitotic 4E-BP1 isoform (δ) did not interact with eIF4E, whereas a distinct 4E-BP1 phospho-isoform, EB-γ—phosphorylated at Thr-70, Ser-83, and Ser-101—bound to eIF4E during mitosis. Two-dimensional gel electropho-retic analysis corroborated the identity of the phosphorylation marks on the eIF4E-bound 4E-BP1 isoforms and uncovered a population of phosphorylated 4E-BP1 molecules lacking Thr-37/Thr-46–priming phosphorylation. Moreover, proximity ligation assays for phospho–4E-BP1 and eIF4E revealed different in situ interactions during interphase and mitosis. The eIF4E:eIF4G interaction was not inhibited, but rather increased in mitotic cells, consistent with active translation initiation during mitosis. Phospho-defective substitution of 4E-BP1 at Ser-83 did not change global translation or individual mRNA translation profiles as measured by single-cell nascent protein synthesis and eIF4G RNA-immunoprecipitation sequencing. Mitotic 5’-terminal oligopyrimidine RNA translation was active and, unlike interphase translation, resistant to mTOR inhibition. Our findings reveal the phosphorylation profiles of 4E-BP1 isoforms and their interactions with eIF4E throughout the cell cycle and indicate that 4E-BP1 does not specifically inhibit translation initiation during mitosis.
2019-06-14 | GSE131668 | GEO
Project description:Spinal microglia play a pivotal role in the development of neuropathic pain. Peripheral nerve injury induces changes in the transcriptional profile of microglia, including increased expression of components of translational machinery. Whether microglial protein synthesis is stimulated following nerve injury and has a functional role in mediating pain hypersensitivity is unknown. Here, we show that nascent protein synthesis is upregulated in spinal microglia following peripheral nerve injury. Stimulating mRNA translation in microglia, via selective ablation of the translational repressor, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), promoted the transition of microglia to a reactive state and induced mechanical hypersensitivity. Conversely, inhibiting microglial translation by expressing mutant 4E-BP1 in microglia attenuated their peripheral nerve injury-induced activation and alleviated neuropathic pain. Thus, the stimulation of 4E-BP1-dependent translation promotes microglia reactivity and mechanical hypersensitivity, whereas its inhibition alleviates neuropathic pain.
2024-01-31 | GSE254472 | GEO
Project description:Activation of the mechanistic target of rapamycin complex 1 (mTORC1) contributes to the development of chronic pain. However, the specific mechanisms by which mTORC1 causes hypersensitivity remain elusive. The eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) is a key mTORC1 downstream effector that represses translation initiation. Here we show that nociceptor-specific deletion of 4E-BP1, mimicking activation of mTORC1-dependent translation, is sufficient to cause mechanical hypersensitivity.
2023-03-27 | GSE227978 | GEO
Project description:Translation initiation is a rate-limiting step in protein synthesis. The eukaryotic translation initiation factor 4E (eIF4E) plays an essential role in the translation initiation process. However, how eIF4E-dependent translation initiation regulates plant growth and development remains not fully understood. In this study, we have found that Arabidopsis eIF4E proteins distribute both in the nucleus and cytoplasm, and only cytoplasmic eIF4E is implicated in the control of flowering time. Results of profiling the genome-wide translation by Ribo-tag sequencing further reveal that eIF4E may regulate plant flowering by affecting homeostatic translation of flowering-time genes, including the Central Oscillator Genes (COGs). Consistent with the hypothesis that transcription-translation feedback loop is the core mechanism to drive the oscillation of circadian clock, we show that the eIF4E-dependent translation modulates the rhythmic oscillation of protein abundance of the clock-related genes (CCGs). Together, our study provides mechanistic insights into how the protein translation regulates multiple developmental processed in Arabidopsis including circadian clock and photoperiodic flowering.
2023-10-25 | GSE245858 | GEO
Project description:Methyl-7-guanosine (m7G) “capping” of coding and some noncoding RNAs is critical for their maturation and subsequent activity. Here, we discovered that eukaryotic translation initiation factor 4E(eIF4E), itself a cap-binding protein, drives the expression of the capping machinery and the increased capping efficiency of ∼100 coding and noncoding RNAs. This dataset collects transcriptomic data for quantitative cap immunoprecipitation (CapIP) assay in eIF4E-Flag or vector stable U2Os cells.
2020-09-30 | GSE158728 | GEO
Project description:Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs accelerates cellular senescence, compromises mitochondrial respiration and increases mitochondrial ROS production. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of the complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These findings together demonstrate that 4E-BP1 functions as a geroprotector to alleviate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III and provide a new potential target to counteract human stem cell senescence.
2023-05-10 | PXD033301 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) relies on hyper-activated protein synthesis. Consistently, human and mouse PDAC lose expression of the translational repressor and mTOR target 4E-BP1. Using genome-wide polysome-profiling, we here explore mRNAs whose translational efficiencies depend on the mTOR/4E-BP1 axis in Miapaca-2 cells. This was performed by isolating cytoplasmic and efficiently translated (heavy polysome-associated) mRNAs from MiaPaca-2 cells upon PP242-mediated mTOR inhibition
2019-09-18 | GSE137553 | GEO
Project description:Caf20p is one of two Saccharomyces cerevisiae eIF4E binding proteins (4E-BPs) involved in translational control. Both 4E-BPs inhibit translation of a different subset of mRNAs, indicating that 4E-BPs bind specific targets. We used normal and mutated Caf20p to perform RIP-Seq analyses in order to explore the ability of Caf20p for binding mRNAs in 4E-dependent and 4E-independent manners.
2015-09-30 | E-MTAB-2892 | biostudies-arrayexpress
Project description: Not available
| S-EPMC6682726 | biostudies-literature
Project description:One of the most regulated steps of translation initiation is the recruitment of an mRNA by the translation machinery. In eukaryotes, this step is mediated by the 5M-BM-4end cap-binding factor eIF4E bound to the bridge protein eIF4G and forming the eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the antigenically distinct eIF4F and eIF(iso)4F complexes proposed to mediate selective translation. Using a microarray analysis of polyribosome- and non-polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type [WT] and eIF(iso)4E knockout mutant [AteIF(iso)4E-1] seedlings we found 79 transcripts shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the opposite behavior in the mutant. The translationally decreased mRNAs were overrepresented in root-preferentially expressed genes and proteins from the endomembrane system, including several transporters such as the phosphate transporter PHOSPHATE1 (PHO1), Sucrose transporter 3 (SUC3), the ABC transporter-like with ATPase activity (MRP11) and five electron transporters, as well as signal transduction-, protein modification- and transcription-related proteins. For transcriptional analysis used total RNA of AteIF(iso)4E-1 seedlings of 15 days old to known the changes on transcripts leves by the eIF(iso)4E absence, using as control Wt seedlings. The experiments were performed in duplicate, and swap analysis were done. For translational analysis, used non-polysomal and polysomal RNA of AteIF(iso)4E-1 seedlings of 15 days old in order to known the transcripts that are modified in their translational levels by the eIF(iso)4E absence, using as control non polysomal and polysomal RNA of Wt seddlings.
2013-07-26 | E-GEOD-29386 | biostudies-arrayexpress