4E-BP1

Summary

Gene Symbol: 4E-BP1
Description: eukaryotic translation initiation factor 4E binding protein 1
Alias: 4E-BP1, 4EBP1, BP-1, PHAS-I, eukaryotic translation initiation factor 4E-binding protein 1, eIF4E-binding protein 1, phosphorylated heat- and acid-stable protein regulated by insulin 1
Species: human
Products:     4E-BP1

Top Publications

  1. Kim D, Sarbassov D, Ali S, King J, Latek R, Erdjument Bromage H, et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell. 2002;110:163-75 pubmed
    ..We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels. ..
  2. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002;110:177-89 pubmed
    ..in part by regulating p70 S6 kinase alpha (p70alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70alpha...
  3. Castellvi J, Garcia A, Rojo F, Ruiz Marcellan C, Gil A, Baselga J, et al. Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer. Cancer. 2006;107:1801-11 pubmed
    ..and extracellular regulated kinase (ERK) pathways and by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K)...
  4. Abiko F, Tomoo K, Mizuno A, Morino S, Imataka H, Ishida T. Binding preference of eIF4E for 4E-binding protein isoform and function of eIF4E N-terminal flexible region for interaction, studied by SPR analysis. Biochem Biophys Res Commun. 2007;355:667-72 pubmed
  5. Armengol G, Rojo F, Castellvi J, Iglesias C, Cuatrecasas M, Pons B, et al. 4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implications. Cancer Res. 2007;67:7551-5 pubmed
    ..Further investigation into this concept may identify additional funnel factors in the oncogenic pathways and provide potential therapeutic targets. ..
  6. O Reilly K, Warycha M, Davies M, Rodrik V, Zhou X, Yee H, et al. Phosphorylated 4E-BP1 is associated with poor survival in melanoma. Clin Cancer Res. 2009;15:2872-8 pubmed publisher
    ..Therefore, effective inhibition of the pathways responsible for 4E-BP1 phosphorylation should be considered to improve the treatment outcome of metastatic melanoma patients. ..
  7. Jacobson B, De A, Kratzke M, Patel M, Jay Dixon J, Whitson B, et al. Activated 4E-BP1 represses tumourigenesis and IGF-I-mediated activation of the eIF4F complex in mesothelioma. Br J Cancer. 2009;101:424-31 pubmed publisher
    ..IGF-I signalling in mesothelioma cells drives cell proliferation, motility, and tumourigenesis through its ability to activate cap-mediated protein translation complex through PI3K/Akt/mTOR signalling. ..
  8. Kumar A, Greggio E, Beilina A, Kaganovich A, Chan D, Taymans J, et al. The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation. PLoS ONE. 2010;5:e8730 pubmed publisher
    ..Overall, our results suggest that 4E-BP is a relatively poor direct substrate for LRRK2. ..
  9. Nawroth R, Stellwagen F, Schulz W, Stoehr R, Hartmann A, Krause B, et al. S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer. PLoS ONE. 2011;6:e27509 pubmed publisher
    ..Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK. ..

More Information

Publications102 found, 100 shown here

  1. Haghighat A, Mader S, Pause A, Sonenberg N. Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 1995;14:5701-9 pubmed
    ..Thus, translational control by growth factors, insulin and mitogens is affected by changes in the relative affinities of 4E-BP1 and p220 for eIF-4E. ..
  2. Brunn G, Fadden P, Haystead T, Lawrence J. The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus. J Biol Chem. 1997;272:32547-50 pubmed
    ..Thus, our findings indicate that Pro is a determinant of the mTOR protein kinase specificity and that mTOR contributes to the phosphorylation of PHAS-I in cells. ..
  3. Garami A, Zwartkruis F, Nobukuni T, Joaquin M, Roccio M, Stocker H, et al. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell. 2003;11:1457-66 pubmed
    ..Finally, coexpression of a human TSC2 cDNA harboring a disease-associated point mutation in the GAP domain, failed to stimulate Rheb GTPase activity or block Rheb activation of S6K1. ..
  4. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg M, Hall A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol. 2004;6:1122-8 pubmed
    ..mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth. ..
  5. Moerke N, Aktas H, Chen H, Cantel S, Reibarkh M, Fahmy A, et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007;128:257-67 pubmed
    ..The identification of this compound provides a new tool for studying translational control and establishes a possible new strategy for cancer therapy. ..
  6. Imai Y, Gehrke S, Wang H, Takahashi R, Hasegawa K, Oota E, et al. Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila. EMBO J. 2008;27:2432-43 pubmed publisher
    ..Our results suggest that chronic inactivation of 4E-BP by LRRK2 with pathogenic mutations deregulates protein translation, eventually resulting in age-dependent loss of DA neurons. ..
  7. Mader S, Lee H, Pause A, Sonenberg N. The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins. Mol Cell Biol. 1995;15:4990-7 pubmed
    ..These results shed light on the mechanisms of eIF-4F assembly and on the translational regulation by insulin and growth factors. ..
  8. Pause A, Belsham G, Gingras A, Donze O, Lin T, Lawrence J, et al. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature. 1994;371:762-7 pubmed
    ..The action of this new regulator of protein synthesis is therefore modulated by insulin, which acts to stimulate the overall rate of translation and promote cell growth. ..
  9. Burnett P, Barrow R, Cohen N, Snyder S, Sabatini D. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci U S A. 1998;95:1432-7 pubmed
    ..This raises the possibility that, in vivo, an unidentified kinase analogous to p70(S6k) is activated by RAFT1 phosphorylation and acts at the rapamycin-sensitive phosphorylation sites of 4E-BP1. ..
  10. Waskiewicz A, Johnson J, Penn B, Mahalingam M, Kimball S, Cooper J. Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo. Mol Cell Biol. 1999;19:1871-80 pubmed
    ..First, eIF4E is sequestered by binding proteins, such as 4EBP1, in quiescent cells. Mitogens induce the release of eIF4E by stimulating the phosphorylation of 4EBP1...
  11. Gingras A, Gygi S, Raught B, Polakiewicz R, Abraham R, Hoekstra M, et al. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev. 1999;13:1422-37 pubmed
    ..Taken together, our results suggest that 4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylation of the carboxy-terminal serum-sensitive sites. ..
  12. Gingras A, Raught B, Gygi S, Niedzwiecka A, Miron M, Burley S, et al. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 2001;15:2852-64 pubmed
    ..Finally, we show that phosphorylation of Ser 65 and Thr 70 alone is insufficient to block binding to eIF4E, indicating that a combination of phosphorylation events is necessary to dissociate 4E-BP1 from eIF4E. ..
  13. Sancak Y, Thoreen C, Peterson T, Lindquist R, Kang S, Spooner E, et al. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell. 2007;25:903-15 pubmed
    ..We propose that the relative strengths of the rheb- and PRAS40-mediated inputs to mTORC1 set overall pathway activity and that insulin activates mTORC1 through the coordinated regulation of both. ..
  14. She Q, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, et al. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell. 2010;18:39-51 pubmed publisher
    ..Thus, 4E-BP1 plays a prominent role in mediating the effects of these pathways in tumors in which they are activated by mutation. ..
  15. Pons B, Armengol G, Livingstone M, Lopez L, Coch L, Sonenberg N, et al. Association between LRRK2 and 4E-BP1 protein levels in normal and malignant cells. Oncol Rep. 2012;27:225-31 pubmed publisher
    ..These results offer new insights into the regulation of total and phosphorylated 4E-BP1. ..
  16. Rojo F, Najera L, Lirola J, Jimenez J, Guzman M, Sabadell M, et al. 4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis. Clin Cancer Res. 2007;13:81-9 pubmed
    ..2 (HER2), epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, Akt, 4E-binding protein 1 (4EBP1), eukaryotic initiation factor 4E, phosphorylated ribosomal protein S6 kinase 1, phosphorylated ribosomal protein ..
  17. Xu H, Jiang W, Feng L, Liu Y, Wu P, Jiang J, et al. Dietary vitamin C deficiency depresses the growth, head kidney and spleen immunity and structural integrity by regulating NF-κB, TOR, Nrf2, apoptosis and MLCK signaling in young grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol. 2016;52:111-38 pubmed publisher
    ..2, 137.5, 135.8 and 129.8 mg/kg diet, respectively. ..
  18. Xu H, Jiang W, Feng L, Liu Y, Wu P, Jiang J, et al. Dietary vitamin C deficiency depressed the gill physical barriers and immune barriers referring to Nrf2, apoptosis, MLCK, NF-?B and TOR signaling in grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. Fish Shellfish Immunol. 2016;58:177-192 pubmed publisher
    ..8, 156.6, 110.8, 57.8 and 134.9 mg/kg diet, respectively. ..
  19. Pan F, Feng L, Jiang W, Jiang J, Wu P, Kuang S, et al. Methionine hydroxy analogue enhanced fish immunity via modulation of NF-?B, TOR, MLCK, MAPKs and Nrf2 signaling in young grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol. 2016;56:208-228 pubmed publisher
    ..07, 5.21, 5.76, 5.90, 5.88, 5.80, 6.22, 5.68 and 6.85 g/kg diet, respectively. ..
  20. Han G, Yang H, Wang Y, Zhang R, Tashiro K, Bungo T, et al. Effects of in ovo feeding of L-leucine on amino acids metabolism and heat-shock protein-70, and -90 mRNA expression in heat-exposed chicks. Poult Sci. 2019;98:1243-1253 pubmed publisher
    ..Attenuated gene expressions of HSP-70 and -90 under heat stress further suggests that in ovo feeding of L-Leu may afford thermotolerance in broilers. ..
  21. Anthony T, Reiter A, Anthony J, Kimball S, Jefferson L. Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed rats. Am J Physiol Endocrinol Metab. 2001;281:E430-9 pubmed
    ..Additionally, the translation of rp mRNAs is preferentially repressed in association with decreased S6K1 phosphorylation...
  22. Wu P, Pan F, Feng L, Jiang W, Jiang J, Kuang S, et al. Methionine hydroxy analogue supplementation modulates gill immunological and barrier health status of grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol. 2018;74:637-648 pubmed publisher
    ..01?g/kg methionine basal were estimated by quadratic regression curve, such as 5.49, 6.17 and 6.02?g/kg diet bases on the defence against gill-rot, malondialdehyde content and LZ activity in the gill, respectively. ..
  23. Zhuang F, Li M, Gao X, Wang Y, Wang D, Ma X, et al. The antidepressant-like effect of alarin is related to TrkB-mTOR signaling and synaptic plasticity. Behav Brain Res. 2016;313:158-171 pubmed publisher
    ..reductions of p70S6K and post-synaptic density 95 (PSD-95) mRNA levels, and of phospho-mTOR and phospho-4EBP1 in the prefrontal cortex, hippocampus, hypothalamus, and olfactory bulb...
  24. Golick L, Han Y, Kim Y, Park S. BRD7 regulates the insulin-signaling pathway by increasing phosphorylation of GSK3β. Cell Mol Life Sci. 2018;75:1857-1869 pubmed publisher
    ..These findings show a novel basis for understanding the molecular dynamics of glucose metabolism and suggest the unique function of BRD7 in the regulation of glucose homeostasis. ..
  25. Kumar V, Pandey P, Sabatini D, Kumar M, Majumder P, Bharti A, et al. Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation. EMBO J. 2000;19:1087-97 pubmed
    ..These findings demonstrate that PKCdelta associates with RAFT1 and thereby regulates phosphorylation of 4E-BP1 and cap-dependent initiation of protein translation. ..
  26. Gordeev S, Bykova T, Zubova S, Aksenov N, Pospelova T. [Antiapoptotic gene bcl-2 prevents cellular senescence program reactivation induced by histone deacetylase inhibitor sodium butyrate in E1A and cHa-ras transformed rat fibroblasts]. Tsitologiia. 2015;57:135-43 pubmed
    ..The set of analyzed cellular senescence markers suggests that a high level of apoptosis resistance gene bcl-2 expression prevents the realization of tumor-suppressor senescence program induced by HDACi sodium butyrate treatment. ..
  27. Caldow M, Ham D, Chee A, Trieu J, Naim T, Stapleton D, et al. Muscle-specific deletion of SOCS3 does not reduce the anabolic response to leucine in a mouse model of acute inflammation. Cytokine. 2017;96:274-278 pubmed publisher
    ..Muscle-specific SOCS3 deletion did not alter the response of AKT, mTOR, S6 or 4EBP1 under any treatment conditions...
  28. Passos G, Camargo J, Ferrari K, Saad M, de Mattos A, Reis L. Intravesical Thalidomide boosts bacillus Calmette-Guérin (BCG) in non-muscle invasive bladder cancer treatment. Med Oncol. 2017;35:3 pubmed publisher
    ..Intravesical BCG-Thalidomide might represent a significant increment in NMIBC treatment, suggesting p70S6K1, HIF-1 and VEGF as potential molecular target candidates in a clinically relevant immune competent NMIBC model. ..
  29. Pinheiro C, de Queiroz J, Guimarães Ferreira L, Vitzel K, Nachbar R, de Sousa L, et al. Local injections of adipose-derived mesenchymal stem cells modulate inflammation and increase angiogenesis ameliorating the dystrophic phenotype in dystrophin-deficient skeletal muscle. Stem Cell Rev. 2012;8:363-74 pubmed publisher
    ..These results suggest that ADMSC transplantation modulates inflammation and improves muscle tissue regeneration, ameliorating the dystrophic phenotype in dystrophin-deficient mice. ..
  30. Nishi T, Iwasaki K, Ohashi N, Tanaka C, Kobayashi D, Nakayama G, et al. Phosphorylation of 4E-BP1 predicts sensitivity to everolimus in gastric cancer cells. Cancer Lett. 2013;331:220-9 pubmed publisher
    ..In conclusion, phosphorylation of 4E-BP1 may be a predictive biomarker of everolimus sensitivity in gastric cancer. ..
  31. Jesus T, Oliveira P, Silva J, Barros A, Ferreira R, Sousa M, et al. Mammalian target of rapamycin controls glucose consumption and redox balance in human Sertoli cells. Fertil Steril. 2016;105:825-833.e3 pubmed publisher
    ..We show that mTOR regulates the nutritional support of spermatogenesis by hSCs and redox balance in these cells. ..
  32. Azar R, Lasfargues C, Bousquet C, Pyronnet S. Contribution of HIF-1? in 4E-BP1 gene expression. Mol Cancer Res. 2013;11:54-61 pubmed publisher
    ..These data therefore suggest that HIF-1? contributes to 4E-BP1 gene expression under different conditions. ..
  33. Simmons A, Scurrah C, McKinley E, Herring C, Irish J, Washington M, et al. Impaired coordination between signaling pathways is revealed in human colorectal cancer using single-cell mass cytometry of archival tissue blocks. Sci Signal. 2016;9:rs11 pubmed
    ..Specifically, coregulation of the kinases p38 and ERK, the translation regulator 4EBP1, and the transcription factor CREB in proliferating normal colon cells was lost in CRC...
  34. Asimomytis A, Karanikou M, Rodolakis A, Vaiopoulou A, Tsetsa P, Creatsas G, et al. mTOR downstream effectors, 4EBP1 and eIF4E, are overexpressed and associated with HPV status in precancerous lesions and carcinomas of the uterine cervix. Oncol Lett. 2016;12:3234-3240 pubmed
    ..expression levels of two critical mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous squamous intraepithelial lesions and cancer ..
  35. Zhang J, Jiang W, Liu W, Wu J, Song L, Cheng J, et al. Effective targeting of colorectal cancer cells using TORC1/2 kinase inhibitors in vitro and in vivo. Future Oncol. 2016;12:515-24 pubmed publisher
    ..Rapamycin and PP242 inhibit phosphorylation of Akt, ribosomal S6 kinase, 4EBP1 and mTOR...
  36. Notario L, Alari Pahissa E, Albentosa A, Leiva M, Sabio G, Lauzurica P. Anti-CD69 therapy induces rapid mobilization and high proliferation of HSPCs through S1P and mTOR. Leukemia. 2018;32:1445-1457 pubmed publisher
    ..These results suggest that anti-CD69 mAbs are putative novel candidates for mobilization strategies. ..
  37. Lee V, Healy T, Fonseca B, Hayashi A, Proud C. Analysis of the regulatory motifs in eukaryotic initiation factor 4E-binding protein 1. FEBS J. 2008;275:2185-99 pubmed publisher
    ..These data provide important information on the structural requirements for efficient signalling downstream of mTORC1. ..
  38. Sutton L, Caron M. Essential role of D1R in the regulation of mTOR complex1 signaling induced by cocaine. Neuropharmacology. 2015;99:610-9 pubmed publisher
    ..Together, our data supports a mechanism whereby mTORC1 signaling is activated by cocaine administration through the stimulation of D1R. ..
  39. Velásquez C, Cheng E, Shuda M, Lee Oesterreich P, Pogge von Strandmann L, Gritsenko M, et al. Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation. Proc Natl Acad Sci U S A. 2016;113:8466-71 pubmed publisher
  40. Fan Q, Nicolaides T, Weiss W. Inhibiting 4EBP1 in Glioblastoma. Clin Cancer Res. 2018;24:14-21 pubmed publisher
    ..have also been unsuccessful or uncertain, in part, because rapamycin inefficiently blocks the mTORC1 target 4EBP1 and feeds back to activate PI3K-AKT signaling...
  41. Yang H, Ye X, Zhang X, Li X, Fu Q, Tang Z. Intracellular osteopontin negatively regulates toll-like receptor 4-mediated inflammatory response via regulating GSK3β and 4EBP1 phosphorylation. Cytokine. 2018;108:89-95 pubmed publisher
    ..Moreover, as a down-stream target of Akt, 4EBP1 was hypo-phosphorylated in OPN-/- macrophages compared to 4EBP1 in WT macrophages...
  42. Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, et al. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem. 2003;278:15461-4 pubmed
  43. Kaur S, Lal L, Sassano A, Majchrzak Kita B, Srikanth M, Baker D, et al. Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signaling. J Biol Chem. 2007;282:1757-68 pubmed
    ..Taken altogether, our data suggest an important role for mTOR-dependent pathways in IFN signaling and identify 4E-BP1 and TSC1-TSC2 as key components in the generation of IFN-dependent biological responses. ..
  44. Roh M, Lee J, Kang K, Nam H, Jung S, Kim K, et al. Phosphorylated 4E-binding protein 1 expression is associated with poor prognosis in small-cell lung cancer. Virchows Arch. 2015;467:667-673 pubmed
  45. Liontos M, Trigka E, Korkolopoulou P, Tzannis K, Lainakis G, Koutsoukos K, et al. Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients. World J Urol. 2017;35:411-419 pubmed publisher
    ..2 vs. 16.9 months, P = 0.001). Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed. ..
  46. Dilling M, Germain G, Dudkin L, Jayaraman A, Zhang X, Harwood F, et al. 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. J Biol Chem. 2002;277:13907-17 pubmed
    ..These results suggest that the 4E-BP:eIF4E ratio is an important determinant of rapamycin resistance and controls certain aspects of the malignant phenotype. ..
  47. Li C, Fang F, Chen Y, Liu T, Chan T, Yu S, et al. Overexpressed Fatty Acid Synthase in Gastrointestinal Stromal Tumors: Targeting a Progression-Associated Metabolic Driver Enhances the Antitumor Effect of Imatinib. Clin Cancer Res. 2017;23:4908-4918 pubmed publisher
    ..C75 represses KIT transactivation, abrogates PI3K/AKT/mTOR activation, and provides a rationale for dual blockade of KIT and FASN in treating imatinib-resistant GISTs. Clin Cancer Res; 23(16); 4908-18. ©2017 AACR. ..
  48. Rapley J, Oshiro N, Ortiz Vega S, Avruch J. The mechanism of insulin-stimulated 4E-BP protein binding to mammalian target of rapamycin (mTOR) complex 1 and its contribution to mTOR complex 1 signaling. J Biol Chem. 2011;286:38043-53 pubmed publisher
  49. Kipp K, Rezaei M, Lin L, Dewey E, Weimbs T. A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. Am J Physiol Renal Physiol. 2016;310:F726-F731 pubmed publisher
    ..The two major branches of mTORC1 signaling, S6 and 4EBP1, are both suppressed in cyst-lining cells by RFI, suggesting that this dietary regimen may be more broadly ..
  50. Wang H, Wang J, Zhang J, Jin S, Li H. Role of PI3K/AKT/mTOR signaling pathway in DBP-induced apoptosis of testicular sertoli cells in vitro. Environ Toxicol Pharmacol. 2017;53:145-150 pubmed publisher
    ..It is speculated that PTEN/PI3K/AKT/mTOR signaling pathway plays an important role in DBP-induced apoptosis of testicular Sertoli cells in rats. ..
  51. Duan P, Hu C, Quan C, Yu T, Zhou W, Yuan M, et al. 4-Nonylphenol induces apoptosis, autophagy and necrosis in Sertoli cells: Involvement of ROS-mediated AMPK/AKT-mTOR and JNK pathways. Toxicology. 2016;341-343:28-40 pubmed publisher
    ..of (Ser473)p-Akt/Akt, (Thr1462)p-TSC2/TSC2, (Ser2448)p-mTOR/mTOR, (Thr389)p-p70S6K/p70S6K and (Thr37/45)p-4EBP1/4EBP1...
  52. Li J, Kanasaki M, Xu L, Kitada M, Nagao K, Adachi Y, et al. A ketogenic amino acid rich diet benefits mitochondrial homeostasis by altering the AKT/4EBP1 and autophagy signaling pathways in the gastrocnemius and soleus. Biochim Biophys Acta Gen Subj. 2018;1862:1547-1555 pubmed publisher
    ..morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles...
  53. Li S, Sun S, Gao J, Sun F. Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells. Oncol Lett. 2016;12:5059-5067 pubmed publisher
    ..Therefore, the present research suggests that wogonin combined with NAC may be a novel combination therapy for clinical pancreatic cancer therapy trials. ..
  54. Nishida H, Ikegami A, Kaneko C, Kakuma H, Nishi H, Tanaka N, et al. Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats. PLoS ONE. 2015;10:e0128805 pubmed publisher
    ..These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles. ..
  55. Liu G, Zhong M, Guo C, Komatsu M, Xu J, Wang Y, et al. Autophagy is involved in regulating influenza A virus RNA and protein synthesis associated with both modulation of Hsp90 induction and mTOR/p70S6K signaling pathway. Int J Biochem Cell Biol. 2016;72:100-108 pubmed publisher
    ..This regulation is associated with modulation of Hsp90 induction and mTOR/p70S6K signaling pathway. Our results provide important evidence for the role of autophagy in IAV replication and the mechanisms underlying the regulation. ..
  56. Duplanty A, Budnar R, Luk H, Levitt D, Hill D, McFarlin B, et al. Effect of Acute Alcohol Ingestion on Resistance Exercise-Induced mTORC1 Signaling in Human Muscle. J Strength Cond Res. 2017;31:54-61 pubmed publisher
    ..This study provides evidence that alcohol should not be ingested after RE as this ingestion could potentially hamper the desired muscular adaptations to RE by reducing anabolic signaling, at least in men. ..
  57. Heesom K, Gampel A, Mellor H, Denton R. Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1). Curr Biol. 2001;11:1374-9 pubmed
    ..Crucially, the increased phosphorylation of 4E-BP1 during mitosis results in its complete dissociation from eIF-4E. ..
  58. Averous J, Fonseca B, Proud C. Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. Oncogene. 2008;27:1106-13 pubmed
  59. Morotomi Yano K, Oyadomari S, Akiyama H, Yano K. Nanosecond pulsed electric fields act as a novel cellular stress that induces translational suppression accompanied by eIF2? phosphorylation and 4E-BP1 dephosphorylation. Exp Cell Res. 2012;318:1733-44 pubmed publisher
    ..These results provide new mechanistic insights into nsPEF action and implicate the therapeutic potential of nsPEFs for stress response-associated diseases. ..
  60. Marabita M, Baraldo M, Solagna F, Ceelen J, Sartori R, Nolte H, et al. S6K1 Is Required for Increasing Skeletal Muscle Force during Hypertrophy. Cell Rep. 2016;17:501-513 pubmed publisher
    ..These findings identify S6K1 as a crucial player for maintaining muscle function during hypertrophy. ..
  61. Kang P, Wang X, Wu H, Zhu H, Hou Y, Wang L, et al. Glutamate alleviates muscle protein loss by modulating TLR4, NODs, Akt/FOXO and mTOR signaling pathways in LPS-challenged piglets. PLoS ONE. 2017;12:e0182246 pubmed publisher
    ..05). Moreover, Glu supplementation increased p-Akt/t-Akt ratio (P<0.05) in gastrocnemius muscle, and p-4EBP1/t-4EBP1 ratio in both gastrocnemius and LD muscles (P<0.05)...
  62. Qaisiya M, Mardešić P, Pastore B, Tiribelli C, Bellarosa C. The activation of autophagy protects neurons and astrocytes against bilirubin-induced cytotoxicity. Neurosci Lett. 2017;661:96-103 pubmed publisher
    ..mTORC1 inactivation by UCB was confirmed by phosphorylation of 4EBP1. UCB induced LC3-II conversion was completely prevented by pretreating cells with the calcium chelator BAPTA and ..
  63. Jin L, Jin M, Nam A, Park J, Bang J, Oh D, et al. Anti-tumor effects of NVP-BKM120 alone or in combination with MEK162 in biliary tract cancer. Cancer Lett. 2017;411:162-170 pubmed publisher
    ..Our findings thus support the clinical development of BKM120 monotherapy or BKM120/MEK162 combination therapy for the treatment of BTC. ..
  64. Grolleau A, Sonenberg N, Wietzerbin J, Beretta L. Differential regulation of 4E-BP1 and 4E-BP2, two repressors of translation initiation, during human myeloid cell differentiation. J Immunol. 1999;162:3491-7 pubmed
    ..Taken together, these data provide evidence for differential regulation of the translational machinery during human myeloid differentiation, specific to the monocytic/macrophage pathway or to the granulocytic pathway. ..
  65. Navadgi Patil V, Burgers P. Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. J Biol Chem. 2008;283:35853-9 pubmed publisher
    ..Our studies suggest that Dpb11 and 9-1-1 may partially compensate for each other during yeast checkpoint function. ..
  66. Hackl E. Limited proteolysis of natively unfolded protein 4E-BP1 in the presence of trifluoroethanol. Biopolymers. 2014;101:591-602 pubmed publisher
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    ..by altering the cap-binding activity of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1)...
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    ..Expression of phosphorylated p70S6K1, RPS6, and 4EBP1 proteins, as well as total mechanistic target of rapamycin (mTOR) protein, decreased in Holsteins fed HIG, whereas ..
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    ..We attempt to investigate the effect of metformin on Ki-67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by immunohistochemical staining...
  71. Yu Z, Lin W, Rui Z, Jihong P. Fibroblast-like synoviocyte migration is enhanced by IL-17-mediated overexpression of L-type amino acid transporter 1 (LAT1) via the mTOR/4E-BP1 pathway. Amino Acids. 2018;50:331-340 pubmed publisher
    ..We found that BCH exposure reduced the phosphorylation of mTOR and its downstream target 4EBP1, radiolabeled leucine uptake, and migration of RA FLS...
  72. Takahashi T, Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, et al. Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro. Genes Cells. 2000;5:765-75 pubmed
    ..effectors such as p70 S6 kinase alpha (p70 alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1)...
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    ..behavior of the complex formation of eIF4E with either or both mRNA cap analogue (m7GTP, m7GpppA, or m7GpppG) and 4EBP1 has been investigated by spectroscopic measurements...
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    Insulin stimulates protein synthesis by promoting phosphorylation of the eIF4E-binding protein, 4EBP1. This effect is rapamycin-sensitive and mediated by mammalian target of rapamycin (mTOR) complex 1 (mTORC1), a signaling complex ..
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    ..Altogether, these findings strongly suggest a key regulatory role for the translational repressor 4E-BP1 in the generation of retinoid-dependent functional responses. ..
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    ..This work therefore highlights a novel role of the oncogenic mTORC1-eIF4E pathway, namely, the promotion of formation of antiapoptotic SG. ..
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    ..Consistent with these observations, we found that RSV induces dephosphorylation of 4EBP1 (eIF4E-binding protein), an important cellular translation factor...
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    ..In conclusion, p?4E?BP1 protein expression appears to be upregulated in CRC, suggesting that it may be a suitable biomarker for predicting CRC prognosis. ..
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    ..In summary, PRL-stimulated phosphorylation of mTOR is mediated by PI3K. PRL-activated mTOR may phosphorylate p70S6K and 4E-BP1 by restraining PP2A. ..
  85. Seki N, Takasu T, Sawada S, Nakata M, Nishimura R, Segawa Y, et al. Prognostic significance of expression of eukaryotic initiation factor 4E and 4E binding protein 1 in patients with pathological stage I invasive lung adenocarcinoma. Lung Cancer. 2010;70:329-34 pubmed publisher
    Both eukaryotic initiation factor 4E (eIF4E) and eIF4E binding protein 1 (4E-BP1) are involved in the malignant progression of human cancers...
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    ..explore the expression and their correlation of mammalian target of rapamycin (mTOR) and EIF4E binding protein1 (4EBP1) in laryngeal squamous cell carcinoma (LSCC)...
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    ..In addition, Sal-induced activation of GSK3β, TSC2, and 4EBP1 was abolished by MK-2206 cotreatment...
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    ..Therefore, the effectiveness of inhibitors of mTOR complexes can be estimated by their ability to suppress both mTORC1 and 2 and their ability to impede both cell proliferation and migration. ..
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    ..Enhanced MAPK1/3 phosphorylation in luminal breast cancer is related to PIK3CA exon-specific mutations and correlated with favorable prognosis especially when located in the nuclei of tumor cells. ..
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  91. Zhang Y, Wang P, Lin S, Mercier Y, Yin H, Song Y, et al. mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources. Amino Acids. 2018;50:105-115 pubmed publisher
    ..Taken together, mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources. ..
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    ..Follow-up studies are needed to determine if the observed peripheral upregulation of transcripts within the NRG-ErbB signaling pathway are specific to TRS or are a general blood-based marker of schizophrenia...