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EIF4E — MTOR

Pathways - manually collected, often from reviews:

• NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → 4E-BP1/eIF4E complex (EIF4EBP1-EIF4E) (modification, activates)
  Gingras et al., Genes Dev 1999*, Nojima et al., J Biol Chem 2003, Schalm et al., Curr Biol 2003*, Beugnet et al., J Biol Chem 2003*, Brunn et al., Science 1997*, Burnett et al., Proc Natl Acad Sci U S A 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met): mTORC1 complex (MTOR-MLST8-RPTOR) → 4E-BP1/eIF4E complex (EIF4EBP1-EIF4E) (modification, activates)
  Moumen et al., Development 2007
  Evidence: mutant phenotype, assay
• Reactome Reaction: MTOR → EIF4E (reaction) Hara et al., Cell 2002, Ali et al., J Biol Chem 2005
• WikiPathways Insulin Signaling: MTOR → EIF4EBP1/EIF4E (activation)

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Intact Interaction: Complex of 13 proteins (association, anti bait coimmunoprecipitation) Ma et al., Cell 2008
• IRef Intact Interaction: Complex of NCBP1-EIF3B-MTOR-EIF4E (association, anti bait coimmunoprecipitation) Ma et al., Cell 2008

Text-mined interactions from Literome

Tinton et al., FEBS Lett 1999 : This enhanced association of 4E-BP1 with eIF-4E might be mediated by mTOR
Kimball et al., Am J Physiol Endocrinol Metab 2000 : The results reveal that treating 18-h fasted pigs with rapamycin, a specific inhibitor of mTOR , before feeding prevented the activation of S6K1 and the changes in eIF4F complex formation observed in skeletal muscle and liver after feeding
Davies et al., J Biol Chem 2004 (MAP Kinase Signaling System) : In addition, CD40 ligation was found to mediate a PI3K- and mammalian target of rapamycin (mTOR) dependent phosphorylation of 4E-BP1 and its subsequent dissociation from the mRNA cap binding protein eIF4E as well as an ERK dependent phosphorylation of eIF4E , thus promoting translation initiation
Salaün et al., Exp Cell Res 2004 : It has been shown that FRAP/mTOR is required for eIF4E release from the translational repressor 4E-BP, a process that occurs upstream of de novo cyclin B synthesis
Sun et al., Cancer Res 2005 (Carcinoma, Non-Small-Cell Lung...) : Activation of Akt and eIF4E survival pathways by rapamycin mediated mammalian target of rapamycin inhibition
Petroulakis et al., Br J Cancer 2006 (Cell Transformation, Neoplastic...) : mTOR affects the activity of the eIF4F complex by phosphorylating repressors of the eIF4F complex, the eIF4E binding proteins
Harris et al., EMBO J 2006 : This novel effect was blocked by rapamycin and other inhibitors of mTOR , and it required neither eIF4E binding to eIF4G nor eIF3 binding to the 40S ribosomal subunit
Prabhu et al., Oncogene 2007 (Leukemia, Myelogenous, Chronic, BCR-ABL Positive) : Experiments with rapamycin and the Bcr-Abl inhibitor, imatinib mesylate, in Bcr-Abl expressing cell lines and primary CML cells indicated that Bcr-Abl and mTORC1 induced formation of the translation initiation complex, eIF4F
Petroulakis et al., Br J Cancer 2007 : mTOR affects the activity of the eIF4F complex by phosphorylating repressors of the eIF4F complex, the eIF4E binding proteins
Wang et al., Mol Cell Biol 2007 (Neoplasms) : In this study, we focused on revealing the mechanism by which mTOR inhibition increases eIF4E phosphorylation ... Importantly, mTOR inhibitors lost their ability to increase eIF4E phosphorylation only in cells where both Mnk1 and Mnk2 were knocked out, indicating that mTOR inhibitors increase eIF4E phosphorylation through a Mnk dependent mechanism ... Given that mTOR inhibitors failed to increase Mnk and eIF4E phosphorylation in phosphatidylinositol 3-kinase (PI3K)-deficient cells, we conclude that mTOR inhibition increases eIF4E phosphorylation through a PI3K dependent and Mnk mediated mechanism
Jin et al., Eur J Pharmacol 2008 (Neoplasm Invasiveness) : TCN could be a new HIF-1 targeted anticancer agent and be effective on mammalian target of rapamycin (mTOR) targeted cancer therapy, in which mTOR inhibition increases eIF4E phosphorylation
Chen et al., Lab Invest 2010 : Here, we show that hydrogen peroxide ( H ( 2 ) O ( 2 ) ), a major oxidant generated when oxidative stress occurs, induced apoptosis of neuronal cells ( PC12 cells and primary murine neurons ), by inhibiting the mammalian target of rapamycin (mTOR) mediated phosphorylation of ribosomal p70 S6 kinase ( S6K1 ) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 ( 4E-BP1 )
Puli et al., Neurochem Res 2010 (Glioblastoma) : In this study we investigated the effect of combination treatment of rapamycin with isoflavones such as genistein and biochanin A on mTOR pathway and activation of Akt and eIF4E in human glioblastoma ( U87 ) cells
Satheesha et al., Molecular cancer 2011 (Breast Neoplasms) : However, higher pre-treatment eIF4E activity was significantly associated with dramatic post-treatment changes in expression of eIF4E and 4E-binding proteins, suggesting that eIF4E is further deregulated in these tumours in response to mTOR inhibition
Melemedjian et al., Molecular pain 2011 (Disease Models, Animal...) : Peripheral nerve injury induced reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity, increased phosphorylation of mTOR and ERK downstream targets, augmented eIF4F complex formation and enhanced nascent protein synthesis
Grosso et al., PloS one 2011 : In spite of this, mTORc1 inhibition reduces eIF4F complex formation, and depresses translocation of TOP mRNAs on polysomes
Fournier et al., Mol Cell Biol 2013 : mTORC1 specifically drives the eIF4E mediated formation of SG through the phosphorylation of 4E-BP1, a key factor known to inhibit formation of the mTORC1 dependent eIF4E-eIF4GI interactions
Pola et al., Cancer Res 2013 : Continuous activation of mTOR despite hypoxia involves release of translation initiation factor eIF4E from its repressor protein 4E-BP1, which is required for vitronectin mediated tumor cell invasion
Hara et al., J Biol Chem 1997 : We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection requires that the rapamycin-resistant mTOR variant retains an active catalytic domain
Hara et al., J Biol Chem 1998 : Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism