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4E-BP1/EIF4EBP1  Gene / cDNA Clone

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HP100086 
MP200714 

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4E-BP1/EIF4EBP1 Related Area

4E-BP1/EIF4EBP1 Related Pathways

    4E-BP1/EIF4EBP1 Summary & Protein Information

    4E-BP1/EIF4EBP1 Background

    Gene Summary: This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation.
    General information above from NCBI
    Subunit structure: Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:12747827). {ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:17368478, ECO:0000269|PubMed:17631896, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:8521827}.
    Domain: The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex. {ECO:0000269|PubMed:12747827}.
    Post-translational: Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E. {ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17525332, ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:9465032}.; Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E. {ECO:0000269|PubMed:22578813}.
    Sequence similarity: Belongs to the eIF4E-binding protein family. {ECO:0000305}.
    General information above from UniProt

    The translational suppressor eIF4E binding protein-1, 4E-BP1 functions as a key regulator in cellular growth, differentiation, apoptosis and survival. The Eif4ebp1 gene, encoding 4E-BP1, is a direct target of a transcription factor activating transcription factor-4 (ATF4), a master regulator of gene expression in stress responses. 4E-BP1 is characterized by its capacity to bind specifically to eIF4E and inhibit its interaction with eIF4G. Phosphorylation of 4E-BP1 regulates eIF4E availability, and therefore, cap-dependent translation, in cell stress. Binding of eIF4E to eIF4G is inhibited in a competitive manner by 4E-BP1. Phosphorylation of 4E-BP1 decreases the affinity of this protein for eIF4E, thus favouring the binding of eIF4G and enhancing translation. 4E-BP1 is important for beta-cell survival under endoplasmic reticulum (ER) stress. 4E-BP1 mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. Recently, 4E-BP1 was found to be a key factor, which converges several oncogenic signals, phosphorylates the molecules, and drives the downstream proliferative signals. Recent studies showed that high expression of phosphorylated 4E-BP-1 (p-4E-BP1) is associated with poor prognosis, tumor progression, or nodal metastasis in different human cancers.

    4E-BP1/EIF4EBP1 Alternative Name

    4E-BP1/EIF4EBP1 Related Studies

  • Azar R, et al. (2008) Phosphatidylinositol 3-kinase-dependent transcriptional silencing of the translational repressor 4E-BP1. Cell Mol Life Sci. 65(19): 3110-7.
  • Tominaga R, et al. (2010) The JNK pathway modulates expression and phosphorylation of 4E-BP1 in MIN6 pancreatic beta-cells under oxidative stress conditions. Cell Biochem Funct. 28(5): 387-93.
  • Ayuso MI, et al. (2010) New hierarchical phosphorylation pathway of the translational repressor eIF4E-binding protein 1 (4E-BP1) in ischemia-reperfusion stress. J Biol Chem. 285(45): 34355-63.
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