Genomes and Genes
Gene Symbol: Eif4ebp1
Description: eukaryotic translation initiation factor 4E binding protein 1
Alias: PHAS-I, eukaryotic translation initiation factor 4E-binding protein 1, 4E-BP1, eIF4E-binding protein 1, phosphorylated heat- and acid-stable protein regulated by insulin 1
- Activated eIF4E-binding protein slows G1 progression and blocks transformation by c-myc without inhibiting cell growthMary Lynch
Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA
J Biol Chem 279:3327-39. 2004..It further identifies G(1) control by translation initiation factors as an essential genetic target of c-myc that is necessary for its ability to transform cells...
- PHAS-I as a link between mitogen-activated protein kinase and translation initiationT A Lin
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110
Science 266:653-6. 1994..Thus, PHAS-I may be a key mediator of the stimulation of protein synthesis by the diverse group of agents and stimuli that activate MAP kinase...
- Molecular mechanisms of mTOR-mediated translational controlXiaoju Max Ma
Department of Research Oncology Diagnostics, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
Nat Rev Mol Cell Biol 10:307-18. 2009..Here, we highlight recent findings on the regulators and effectors of mTOR and discuss specific cases that serve as paradigms for the different modes of mTOR regulation and its control of translation...
- Regulation of 4E-BP1 phosphorylation: a novel two-step mechanismA C Gingras
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
Genes Dev 13:1422-37. 1999..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...
- Dissociation of the eukaryotic initiation factor-4E/4E-BP1 complex involves phosphorylation of 4E-BP1 by an mTOR-associated kinaseK J Heesom
Department of Biochemistry, School of Medical Sciences, University Walk, Bristol, UK
FEBS Lett 457:489-93. 1999..This phosphorylation, which occurs predominantly on S(64), results in the dissociation of 4E-BP1 from eIF-4E...
- Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteinsXuemin Wang
Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, United Kingdom
Mol Cell Biol 25:2558-72. 2005..These data have important implications for understanding signaling downstream of mTOR and the development of new strategies to impair mTOR signaling...
- 4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cellsPeng Duan
MOE Ministry of Education key lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Research Center for Environment and Health, Hubei University of Medicine, Shiyan 442000, China
Toxicol Lett . 2016....
- mTOR/P70S6K promotes spermatogonia proliferation and spermatogenesis in Sprague Dawley ratsHao Xu
Department of Paediatric Research Institute, Children s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
Reprod Biomed Online 32:207-17. 2016..Therefore, we suggest that mTOR plays an important role in spermatogenesis by regulating p70s6k activation and that 4e-bp1 is either directly or indirectly regulated by PI3K. ..
- Rotenone induction of hydrogen peroxide inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E pathways, leading to neuronal apoptosisQian Zhou
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, P R China, Department of Biochemistry and Molecular Biology and Feist Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130 3932
Toxicol Sci 143:81-96. 2015..Our findings suggest that rotenone-induced neuronal loss in PD may be prevented by activating mTOR signaling and/or administering antioxidants...
- Everolimus sensitizes Ras-transformed cells to radiation in vitro through the autophagy pathwayYu Chieh Su
Department of Hematological Oncology, Buddhist Dalin Tzu Chi Hospital, Chiayi 62247, Taiwan, R O C
Int J Mol Med 34:1417-22. 2014..Everolimus-mediated radiosensitization is associated with the autophagy pathway. Thus, everolimus is a novel radiosensitizing agent with potential for use in cancer radiotherapy...
- Characterization of the Raptor/4E-BP1 interaction by chemical cross-linking coupled with mass spectrometry analysisKimberly Coffman
From the Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, Molecular Biology Institute, University of California, Los Angeles, California 90095
J Biol Chem 289:4723-34. 2014..Furthermore, mutations of residues in the RCR decrease the ability of 4E-BP1 to serve as a substrate for mTORC1 in vitro and in vivo. ..
- Prolactin activates mammalian target-of-rapamycin through phosphatidylinositol 3-kinase and stimulates phosphorylation of p70S6K and 4E-binding protein-1 in lymphoma cellsJessica D Bishop
Department of Biochemistry and Molecular Biology, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, B3H 1X5 Canada
J Endocrinol 190:307-12. 2006..In summary, PRL-stimulated phosphorylation of mTOR is mediated by PI3K. PRL-activated mTOR may phosphorylate p70S6K and 4E-BP1 by restraining PP2A...
- Inhibition of Cap-initiation complexes linked to a novel mechanism of eIF4G depletion in acute myocardial ischemiaE P Connolly
Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Cell Death Differ 13:1586-94. 2006..Acute heart ischemia therefore downregulates cap-dependent translation through eIF4E sequestration triggered by eIF4G depletion...
- Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed ratsT G Anthony
Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, PA 17033, USA
Am J Physiol Endocrinol Metab 281:E430-9. 2001..Additionally, the translation of rp mRNAs is preferentially repressed in association with decreased S6K1 phosphorylation...
- Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. Identification of a site phosphorylated by MAP kinase in vitro and in response to insulin in rat adipocytesT A Haystead
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22903
J Biol Chem 269:23185-91. 1994..We conclude that PHAS-I is a substrate for MAP kinase both in vivo and in vitro. As PHAS-I is one of the most prominent insulin-stimulated phosphoproteins in adipocytes, it may qualify as the major MAP kinase substrate in these cells...
- Identification of phosphorylation sites in the translational regulator, PHAS-I, that are controlled by insulin and rapamycin in rat adipocytesP Fadden
Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
J Biol Chem 272:10240-7. 1997..All five sites identified fit a (Ser/Thr)-Pro motif, suggesting that the phosphorylation of PHAS-I in cells is mediated by a proline-directed protein kinase...
- Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycinG J Brunn
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Science 277:99-101. 1997..These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells...
- Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motifAndrew R Tee
Division of Molecular Physiology, School of Life Sciences, Medical Sciences Institute, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
Mol Cell Biol 22:1674-83. 2002..This suggests that the N-terminal sequence of 4E-BP1 is required for optimal regulation of 4E-BPs by insulin...
- The C-terminal residues of Saccharomyces cerevisiae Mec1 are required for its localization, stability, and functionLance F Dasilva
Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada N6A5C1
G3 (Bethesda) 3:1661-74. 2013..Our study supports a role for the C-terminus in Mec1 folding and stability, and suggests a role for the proteasome in regulating Mec1 levels. ..
- Aberrant expression and phosphorylation of 4E-BP1, a main target of mTOR signaling, in rat mammary carcinomas: an association with etiologyMasaru Takabatake
Radiobiology for Children s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4 9 1 Anagawa, Inage Ku, Chiba 263 8555, Japan
In Vivo 25:853-60. 2011....
- Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1D Q Yang
Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105 2794, USA
Nat Cell Biol 2:893-8. 2000..Through this mechanism, a lack of ATM activity probably contributes to some of the metabolic abnormalities, such as poor growth and insulin resistance, reported in ataxia telangiectasia cells and patients with ataxia telangiectasia...
- Hypoxia increases the association of 4E-binding protein 1 with the initiation factor 4E in isolated rat hepatocytesS A Tinton
Unité de Biochimie Toxicologique et Cancérologique, Universite Catholique de Louvain, Brussels, Belgium
FEBS Lett 446:55-9. 1999..Although hypoxia might be signalling via the rapamycin-sensitive pathway by changing eIF-4E availability, such a pathway is unlikely to be responsible for the depression in overall protein synthesis under hypoxia...
- Administration of triiodo-L-thyronine into dorsal hippocampus alters phosphorylation of Akt, mammalian target of rapamycin, p70S6 kinase and 4E-BP1 in ratsLi Sui
Institute of Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China
Neurochem Res 33:1065-76. 2008....
- Control of PHAS-I by insulin in 3T3-L1 adipocytes. Synthesis, degradation, and phosphorylation by a rapamycin-sensitive and mitogen-activated protein kinase-independent pathwayT A Lin
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 270:18531-8. 1995..Rapamycin may inhibit translation initiation by increasing PHAS-I binding to eIF-4E...
- AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractionsDavid M Thomson
Human Performance Laboratory, Department of Exercise and Sport Science, East Carolina University, Greenville, NC 27858, USA
J Appl Physiol (1985) 104:625-32. 2008....
- Nitric oxide mediates NMDA-induced persistent inhibition of protein synthesis through dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 and eukaryotic initiation factor 4G proteolysisValerie Petegnief
Departamento de Isquemia Cerebral y Neurodegeneración, Instituto de Investigaciones Biomédicas de Barcelona, CSIC IDIBAPS, Rossello 161, Barcelona 08036, Spain
Biochem J 411:667-77. 2008..In conclusion, our data show that NO mediates NMDA-induced persistent translation inhibition and suggest that deficient eIF4F activity contributes to this process...
- Global and gene-specific translational regulation in rat lung developmentGail Otulakowski
Program in Physiology and Experimental Medicine, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, ON M5G1X8, Canada
Am J Respir Cell Mol Biol 40:555-67. 2009..Translational regulation of IL-18 and protein phosphatase 1 regulatory (inhibitor) subunit 2 is gene-specific, as these changes contrast with the corresponding global changes in polysome abundance...
- Expression and distribution of mTOR, p70S6K, 4E-BP1, and their phosphorylated counterparts in rat dorsal root ganglion and spinal cord dorsal hornJi Tain Xu
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Brain Res 1336:46-57. 2010..Our findings support the view that mTOR and its downstream effectors do not play a key role in acute pain...
- New hierarchical phosphorylation pathway of the translational repressor eIF4E-binding protein 1 (4E-BP1) in ischemia-reperfusion stressMaría I Ayuso
Department of Investigation, Hospital Ramon y Cajal, 28034 Madrid, Spain
J Biol Chem 285:34355-63. 2010..These data help to elucidate the physiological role of 4E-BP1 phosphorylation in controlling protein synthesis...
- Effect of quality and quantity of dietary protein on 4E-BP1 and S6K1 phosphorylation of brains in aged ratsMiho Ohsumi
Laboratory of Nutritional Biochemistry, School of Food and Nutritional Sciences, COE Program in the 21st Century, The University of Shizuoka, Suruga, Japan
J Nutr Sci Vitaminol (Tokyo) 56:319-25. 2010..The results suggest that the ingestion of a higher quality and quantity of dietary protein stimulates the phosphorylation of 4E-BP1 and S6K1 in the brain and increases the brain protein synthesis in the aged rats...
- Molecular cloning and tissue distribution of PHAS-I, an intracellular target for insulin and growth factorsC Hu
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110
Proc Natl Acad Sci U S A 91:3730-4. 1994..However, in view of its tissue distribution and the fact that the protein is phosphorylated in response to insulin, we speculate that PHAS-I is important in insulin action...
- The endoplasmic reticulum stress-inducible protein Niban regulates eIF2alpha and S6K1/4E-BP1 phosphorylationGuo Dong Sun
Department of Pathology and Oncology, Juntendo University School of Medicine, 2 1 1 Hongo, Tokyo 113 8421, Japan
Biochem Biophys Res Commun 360:181-7. 2007..Additionally, suppression of NIBAN expression in HeLa cells promoted apoptosis. Together these results suggest that Niban is involved in the ER stress response, and that Niban can modulate cell death signaling by regulating translation...
- Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiationJ E Kim
Department of Cell and Structural Biology, University of Illinois at Urbana Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA
Proc Natl Acad Sci U S A 97:14340-5. 2000..These findings uncover a function for the nucleus in the direct regulation of the protein synthesis machinery via extracellular signals...
- Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancerStephen Marshall
Hexos Inc, 18304 NE 153rd Street, Woodinville, WA 98072, USA
Sci STKE 2006:re7. 2006....
- Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscleKatsuhiko Funai
Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington St, Boston, MA 02111, USA
Am J Physiol Regul Integr Comp Physiol 290:R1080-6. 2006..These observations suggest that the anabolic response to muscle stimulation is attenuated with aging and may contribute to the limited capacity of hypertrophy in aged animals...
- Effect of leptin on liver alcohol dehydrogenaseEsteban Mezey
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2195, USA
Biochem Biophys Res Commun 337:1324-9. 2005..The effect of leptin in enhancing translational initiating factors may be of significance in the regulation not only of ADH but also of many other proteins...
- IGF-I activates the eIF4F system in cardiac muscle in vivoThomas C Vary
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Pennsylvania 17033, USA
Mol Cell Biochem 272:209-20. 2005..Furthermore, the results are consistent with a role for assembly of active eIF4G.eIF4E complex and activation of S6K1 in mediating the stimulation of mRNA translation initiation by IGF-I through a PKB/mTOR signaling pathway...
- N-acetyl-cysteine abolishes hydrogen peroxide-induced modification of eukaryotic initiation factor 4F activity via distinct signalling pathwaysA O'Loghlen
Servicio de Bioquimica, Departamento de Investigacion, Hospital Ramon y Cajal, Ctra Colmenar Km 9, 28034 Madrid, Spain
Cell Signal 18:21-31. 2006..Altogether our findings suggest that the effects caused by oxidative stress on eIF4s factors depends on two MAP kinase-independent signal transduction pathways, being at least one of them rapamycin-dependent...
- Endotoxin (LPS) stimulates 4E-BP1/PHAS-I phosphorylation in macrophagesM W Potter
Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
J Surg Res 97:54-9. 2001..Translation initiation can be prevented by small 4E-binding proteins (4E-BP1 or PHAS-I) which must be phosphorylated in order to disengage eIF-4E. We examined whether LPS alters 4E-BP1 phosphorylation in macrophages...
- Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinaseScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Biol Chem 279:54103-9. 2004..Amino acids also enhance AMPK phosphorylation, although to a lesser extent than glucagon and amino acids combined...
- Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscleCharles H Lang
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
J Cell Physiol 203:144-55. 2005..Hence, LPS working via a glucocorticoid-independent mechanism produces a leucine resistance in skeletal muscle that might be expected to impair the ability of this amino acid to stimulate translation initiation and protein synthesis...
- Acute alcohol intoxication enhances myocardial eIF4G phosphorylation despite reducing mTOR signalingThomas C Vary
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, H166, 500 Univ Dr, Hershey, PA 17033, USA
Am J Physiol Heart Circ Physiol 288:H121-8. 2005..eIF4E complex formation, which appear to be independent of changes in phosphorylation of eIF4G but dependent on mTOR...
- Polyamines regulate eukaryotic initiation factor 4E-binding protein 1 gene transcriptionA H Stephenson
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
Biochem Biophys Res Commun 323:204-12. 2004..These data provide a mechanism by which polyamines affect transcription of the 4E-BP1 gene, which in turn affect translation of ODC and perhaps other cap-dependent proteins...
- Arginine and Leucine regulate p70 S6 kinase and 4E-BP1 in intestinal epithelial cellsHidetoshi Ban
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Graduate School of Medicine and Dentistry, Okayama University, Okayama 700 8558, Japan
Int J Mol Med 13:537-43. 2004..In conclusion, l-Arginine regulates p70 S6 kinase activity and phosphorylation of 4E-BP1 through mTOR signaling pathway, which involves system y(+), cationic amino acid transporters...
- Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumorsHeidi L Kenerson
Department of Surgery, University of Washington, Seattle 98195, USA
Cancer Res 62:5645-50. 2002..Our data provide in vivo evidence that the mTOR pathway is aberrantly activated in TSC renal pathology and that treatment with rapamycin appears effective in the preclinical setting...
- Alcohol-Induced Regulation of Hepatic Protein SynthesisTHOMAS VARY; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- EFFECTS OF ALCOHOL ON MOLECULAR AND CELLULAR PATHOLOGYEsteban Mezey; Fiscal Year: 2008..The final objective is to instill in the trainee the ability to approach original questions of research relating to the pathogenesis of damaging effects of alcoholism on the body. ..
- MYOCARDIAL PROTEIN SYNTHESIS AFTER ALCOHOL INTOXICATIONCharles H Lang; Fiscal Year: 2010..Overall, the research design will establish the mechanism by which myocardial protein synthesis is reduced in response to alcohol abuse. ..
- Antiretroviral-Induced Defects in Muscle Protein SynthesisCharles H Lang; Fiscal Year: 2010..Such data is needed to both realize the full potential and avoid possible pitfalls of this drug in the long-term treatment of HIV-infected individuals. ..
- REGULATION OF PROTEIN TURNOVER IN SEPSISScot R Kimball; Fiscal Year: 2010....
- Myocardial Protein Synthesis After Thermal InjuryCharles Lang; Fiscal Year: 2005..Overall, the research will elucidate the mechanisms by which myocardial protein synthesis is reduced after thermal injury, leading to the better understanding and treatment of the resulting cardiomyopathy. - ..