Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA118857 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The usurping of translational control by sustained activation of translation initiation factors is oncogenic. Here we show that the primary negative regulators of these oncogenic initiation factors - the 4E-BP protein family - operate as guardians of a translational control checkpoint in tumor defense. When challenged with the tobacco carcinogen NNK, 4ebp1-/-/4ebp2-/- mice showed increased sensitivity to tumorigenesis compared to their wild type counterparts. The 4E-BP deficient state per se creates pro-oncogenic, genome-wide skewing of the molecular landscape - with translational activation of genes governing angiogenesis, growth and proliferation; and translational activation of the precise cytochrome p450 enzyme isoform (CYP2A5) that bioactivates NNK into mutagenic metabolites. Our study provides in vivo proof for a translational control checkpoint in tumor defense.
2010-06-01 | GSE17406 | GEO
Project description:4E-BP (eIF4E-BP) represses translation initiation by binding to the 5’cap-binding protein eIF4E and inhibiting its activity. Although 4E-BP has been shown to be important in growth control, stress response, cancer, neuronal activity and mammalian circadian rhythms, it is not understood how it preferentially represses a subset of mRNAs. We successfully used hyperTRIBE (Targets of RNA-binding proteins identified by editing) to identify in vivo 4E-BP mRNA targets in both Drosophila and mammals under conditions known to activate 4E-BP. The protein associates with specific mRNAs, and ribosome profiling data show that mTOR inhibition changes the translational efficiency of 4E-BP TRIBE targets compared to non-targets. In both systems, these targets have specific motifs and are enriched in translation-related pathways, which correlate well with the known activity of 4E-BP and suggest that it modulates the binding specificity of eIF4E and contributes to mTOR translational specificity.
2020-08-20 | GSE153346 | GEO
Project description:Refinement of synaptic connections during development requires both the elimination of some inputs and the strengthening of others. It is well accepted that this competitive process takes place throughout the nervous system and relies on synaptic activity. However, the mechanisms that link activity to refinement remain largely unresolved. Here we demonstrate that refinement of preganglionic axons in sympathetic ganglia, a process that depends unequivocally on synaptic activity, involves eukaryotic initiation factor 4E binding protein (4E-BP), a protein that regulates cap-dependent translation. In mice lacking the 3 nicotinic receptor subunit, silent synapses between preganglionic axons and postsynaptic nicotinic neurons do not refine unless synaptic activity is restored, or surprisingly, when 4E-BP is absent. Our findings demonstrate that synapses can refine in the absence of synaptic activity during development and identify 4E-BP as a critical player in this process.
2017-07-26 | MSV000081386 | MassIVE
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:1. Determination of serum expression level of HOTTIP and EIF4EBP1(Eukaryotic translation initiation factor 4E-binding protein 1) .
2. Investigation of the SNP HOTTIP rs1859168 and it’s association with CRC susceptibility.
3. Determination of serum level of Interleukin -6 and its relation to other studied genes.
4. Correlation of the expression of these genes with various stages of CRC to determine the prognostic value of each of them.
| 2365471 | ecrin-mdr-crc
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:The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5' UTR. mTORC1 also controls ATF4 translation through uORFs, but independent of changes in eIF2α phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP) family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery.
2017-04-15 | GSE97384 | GEO
Project description:The eukaryotic elongation factor-2 kinase, eEF2K, restricts protein translation elongation, and was identified as a potential therapeutic target for diverse types of cancers including triple negative breast cancer (TNBC; PMID: 25330770). We have recently found that inhibition of eEF2K synergizes with depletion of eukaryotic translation initiation factor 4E-binding protein 1 (eIF4EBP1; 4E-BP1), a suppressor of eukaryotic protein translation initiation factor 4E (eIF4E), leading to effective growth suppression of TNBC cells in culture. We performed LC-MS/MS analysis following depletion of eEF2K and/or 4EBP in a TNBC cell line, Hs578t (YoungJun Ju & Eldad Zacksenhaus, manuscript in revisions). Depletion of these factors had overlapping effects on the proteome with the highest impact on Collagen containing extracellular matrix (e.g. COL1A1). The complete LC-MS/MS data sets (control vehicle; eEF2K-depletion, 4EBP1-depletion; combined eEF2k plus 4EBP1-depletion) are provided herein.
| MSV000086059 | MassIVE
Project description:Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression-studies have defined canonical signatures of T-cell subsets. Changes in steady-state mRNA levels do, however, often not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4+Foxp3+ regulatory T (TFoxp3+) and CD4+Foxp3- non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T-cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both TFoxp3- and TFoxp3+ cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4+ T-cell subset. CD4+/Foxp3+ and CD4+Foxp3- cells were studied ex vivo or activated in vitro for 36h. Both polysome-associated and cytoplasmic RNA was isolated to enables studies of translational control
2013-06-01 | E-GEOD-45401 | biostudies-arrayexpress
Project description:Mitosis-related phosphorylation of the eukaryotic translation suppressor 4E-BP1 and its interaction with eukaryotic translation initiation factor 4E (eIF4E)
| PRJNA544328 | ENA