Thor

Summary

Gene Symbol: Thor
Description: thor
Alias: 153432_at, 43-BP, 4E-BP, 4E-BP1, 4EBP, 4e-BP, 4e-bp, 4eBP, 4ebp, BcDNA.HL08053, BcDNA:HL08053, CG8846, CT8705, Dm 4E-BP, Dmel\CG8846, Phas1, Thor/EIF4EBP, anon-WO0172774.158, d4E-BP, d4E-BP1, d4EBP, d4e-bp, d4eBP, dthor, eIF4E-BP, l(2)06270, l(2)k07736, l(2)k13517, pp20, thor, thor, 4E binding protein, CG8846-PA, CG8846-PB, Eif4e-binding protein, Thor-PA, Thor-PB, eIF-4E-binding protein, eIF4E binding protein, eif4e-binding protein 4EBP, eukaryotic initiation factor 4E binding protein, eukaryotic initiation factor 4E-binding protein, eukaryotic translation initiation factor 4E binding protein, eukaryotic translation initiation factor 4E-binding protein, insulin-stimulated eIF-4E binding protein, lethal (2) 06270, translation initiation factor 4E binding protein
Species: fruit fly
Products:     Thor

Top Publications

  1. Partridge L, Alic N, Bjedov I, Piper M. Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network. Exp Gerontol. 2011;46:376-81 pubmed publisher
    ..Reduced IIS can act acutely to lower death rate, implying that it may ameliorate the effects of ageing-related damage, rather than preventing it. ..
  2. Cully M, Genevet A, Warne P, Treins C, Liu T, Bastien J, et al. A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1. Mol Cell Biol. 2010;30:481-95 pubmed publisher
    ..These data suggest that p38 is an important positive regulator of TORC1 in both mammalian and Drosophila systems in response to certain stresses and growth factors. ..
  3. Tain L, Mortiboys H, Tao R, Ziviani E, Bandmann O, Whitworth A. Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat Neurosci. 2009;12:1129-35 pubmed publisher
    ..We found that overexpression of the translation inhibitor Thor (4E-BP) can suppress all of the pathologic phenotypes, including degeneration of dopaminergic neurons in Drosophila...
  4. Karpac J, Hull Thompson J, Falleur M, Jasper H. JNK signaling in insulin-producing cells is required for adaptive responses to stress in Drosophila. Aging Cell. 2009;8:288-95 pubmed publisher
    ..Endocrine control of IIS by JNK in IPCs is thus critical for systemic adaptation to stress. ..
  5. Harvey K, Mattila J, Sofer A, Bennett F, Ramsey M, Ellisen L, et al. FOXO-regulated transcription restricts overgrowth of Tsc mutant organs. J Cell Biol. 2008;180:691-6 pubmed publisher
    ..Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species. ..
  6. Libert S, Chao Y, Zwiener J, Pletcher S. Realized immune response is enhanced in long-lived puc and chico mutants but is unaffected by dietary restriction. Mol Immunol. 2008;45:810-7 pubmed
    ..Such upregulation is not observed during DR, suggesting the presence of a mechanism that suppresses immune activity in diet-restricted animals. ..
  7. Alic N, Hoddinott M, Vinti G, Partridge L. Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor. Aging Cell. 2011;10:137-47 pubmed publisher
    ..in phenotypic changes in the adult consistent with down-regulation of IIS, including accumulation of eIF-4E binding protein mRNA, increase in storage lipids, reduced fecundity and enhanced oxidative stress resistance...
  8. Chang Y, Neufeld T. An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell. 2009;20:2004-14 pubmed publisher
    ..Atg1-Atg13 complexes thus function at multiple levels to mediate and adjust nutrient-dependent autophagic signaling. ..
  9. 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. ..

More Information

Publications63

  1. Lee K, Kwon O, Lee J, Kwon K, Min K, Jung S, et al. Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling. Nat Cell Biol. 2008;10:468-75 pubmed publisher
    ..Drosophila sNPF and the evolutionarily conserved mammalian NPY seem to regulate ERK-mediated insulin expression and thus to systemically modulate growth, metabolism and lifespan. ..
  2. Reiling J, Hafen E. The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes Dev. 2004;18:2879-92 pubmed
  3. Bülow M, Aebersold R, Pankratz M, Jünger M. The Drosophila FoxA ortholog Fork head regulates growth and gene expression downstream of Target of rapamycin. PLoS ONE. 2010;5:e15171 pubmed publisher
    ..In summary, our observations show that an alteration of FKH levels has an effect on cellular and organismal size, and that FKH function is required for the growth inhibition and target gene induction caused by low TOR signaling levels. ..
  4. Colombani J, Bianchini L, Layalle S, Pondeville E, Dauphin Villemant C, Antoniewski C, et al. Antagonistic actions of ecdysone and insulins determine final size in Drosophila. Science. 2005;310:667-70 pubmed
    ..Hence, ecdysone counteracts the growth-promoting action of insulins, thus forming a humoral regulatory loop that determines organismal size. ..
  5. Liu S, Lu B. Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster. PLoS Genet. 2010;6:e1001237 pubmed publisher
    ..Our results reveal complex cellular responses to PINK1 inactivation and suggest novel therapeutic strategies through manipulation of the compensatory responses. ..
  6. Demontis F, Perrimon N. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 2010;143:813-25 pubmed publisher
    ..These findings reveal an organism-wide regulation of proteostasis in response to muscle aging and a key role of FOXO/4E-BP signaling in the coordination of organismal and tissue aging. ..
  7. Miron M, Lasko P, Sonenberg N. Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster. Mol Cell Biol. 2003;23:9117-26 pubmed
    ..Surprisingly, RNAi of dAkt also affected insulin-stimulated phosphorylation of dS6K, indicating that dAkt may also play a role in dS6K phosphorylation. ..
  8. Fuss B, Becker T, Zinke I, Hoch M. The cytohesin Steppke is essential for insulin signalling in Drosophila. Nature. 2006;444:945-8 pubmed
    ..Our findings indicate a crucial role of an ARF-GEF in insulin signalling that has implications for understanding insulin-related disorders, such as diabetes and obesity. ..
  9. Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003;13:79-85 pubmed
    ..This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth. ..
  10. Fuda N, Buckley M, Wei W, Core L, Waters C, Reinberg D, et al. Fcp1 dephosphorylation of the RNA polymerase II C-terminal domain is required for efficient transcription of heat shock genes. Mol Cell Biol. 2012;32:3428-37 pubmed publisher
    ..Our results indicate that Fcp1 is required to maintain the pool of initiation-competent unphosphorylated Pol II, and this function is particularly important for the highly transcribed heat shock genes. ..
  11. Hernández G, Altmann M, Sierra J, Urlaub H, Diez del Corral R, Schwartz P, et al. Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila. Mech Dev. 2005;122:529-43 pubmed
    ..Overexpression of eIF4E-1 in wild-type embryos and eye imaginal discs results in phenotypic defects in a dose-dependent manner. ..
  12. Rodriguez A, Zhou Z, Tang M, Meller S, Chen J, Bellen H, et al. Identification of immune system and response genes, and novel mutations causing melanotic tumor formation in Drosophila melanogaster. Genetics. 1996;143:929-40 pubmed
    ..determination of lethal phase and mutant phenotype have identified six novel genes, Dorothy, wizard, toto, viking, Thor and dappled, and one previously identified gene, Collagen IV...
  13. Wessells R, Fitzgerald E, Piazza N, Ocorr K, Morley S, Davies C, et al. d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila. Aging Cell. 2009;8:542-52 pubmed publisher
    ..Here, we show that the Eif4e-binding protein (d4eBP) is sufficient to protect long-term cardiac function against age-related decline and that up-regulation of dEif4e ..
  14. McNeill H, Craig G, Bateman J. Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin pathway in Drosophila. Genetics. 2008;179:843-53 pubmed publisher
    ..Together these data suggest that InR/TOR signaling regulates the timing of differentiation through modulation of EGFR target genes in developing photoreceptors. ..
  15. Gingras A, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15:807-26 pubmed
  16. Bryk B, Hahn K, Cohen S, Teleman A. MAP4K3 regulates body size and metabolism in Drosophila. Dev Biol. 2010;344:150-7 pubmed publisher
    ..Flies lacking MAP4K3 have reduced TORC1 activity detected by phosphorylation of S6K and 4EBP. Furthermore MAP4K3 mutants display phenotypes characteristic of low TORC1 activity and low nutrient availability, ..
  17. LaFever L, Feoktistov A, Hsu H, Drummond Barbosa D. Specific roles of Target of rapamycin in the control of stem cells and their progeny in the Drosophila ovary. Development. 2010;137:2117-26 pubmed publisher
    ..These results uncover specific TOR functions in the control of stem cells versus their differentiating progeny, and reveal parallels between Drosophila and mammalian follicle growth. ..
  18. Bernal A, Kimbrell D. Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity. Proc Natl Acad Sci U S A. 2000;97:6019-24 pubmed
    b>Thor has been identified as a new type of gene involved in Drosophila host immune defense...
  19. Okamoto N, Nakamori R, Murai T, Yamauchi Y, Masuda A, Nishimura T. A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes Dev. 2013;27:87-97 pubmed publisher
    ..We propose that Drosophila uses a secreted decoy to fine-tune systemic growth against fluctuations of circulating insulin levels. ..
  20. Karpac J, Biteau B, Jasper H. Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila. Cell Rep. 2013;4:1250-61 pubmed publisher
    ..Changes in the regulation of Foxo-mediated adaptive responses thus contribute to the age-associated breakdown of metabolic homeostasis. ..
  21. Findlay G, Yan L, Procter J, Mieulet V, Lamb R. A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J. 2007;403:13-20 pubmed
    ..Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3. ..
  22. Marr M, D Alessio J, Puig O, Tjian R. IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback. Genes Dev. 2007;21:175-83 pubmed
  23. Zhang J, Panicker L, Seigneur E, Lin L, House C, Morgan W, et al. Cytoplasmic polyadenylation element binding protein is a conserved target of tumor suppressor HRPT2/CDC73. Cell Death Differ. 2010;17:1551-65 pubmed publisher
  24. Na J, Musselman L, Pendse J, Baranski T, Bodmer R, Ocorr K, et al. A Drosophila model of high sugar diet-induced cardiomyopathy. PLoS Genet. 2013;9:e1003175 pubmed publisher
    ..Our data establish Drosophila as a useful system for exploring specific aspects of diet-induced heart dysfunction and emphasize enzymes within the hexosamine biosynthetic pathway as candidate therapeutic targets. ..
  25. Wang T, Lao U, Edgar B. TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J Cell Biol. 2009;186:703-11 pubmed publisher
    ..Thus, our data indicate that TOR induces cell death by suppressing autophagy and provide direct genetic evidence that autophagy alleviates cell death in several common types of neurodegenerative disease. ..
  26. Hennig K, Colombani J, Neufeld T. TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. J Cell Biol. 2006;173:963-74 pubmed
    ..Our data indicate that endocytosis acts both as an effector function downstream of TOR and as a physiologically relevant regulator of TOR signaling...
  27. Rajan A, Perrimon N. Of flies and men: insights on organismal metabolism from fruit flies. BMC Biol. 2013;11:38 pubmed publisher
  28. Pan D, Dong J, Zhang Y, Gao X. Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol. 2004;14:78-85 pubmed
    ..Here, we review these exciting developments with an emphasis on Drosophila studies and discuss how Drosophila can be a powerful model system for an understanding of the molecular mechanisms of the activity of human disease genes. ..
  29. Gronke S, Clarke D, Broughton S, Andrews T, Partridge L. Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 2010;6:e1000857 pubmed publisher
    ..Evolutionary conservation has thus been accompanied by synergy, redundancy, and functional differentiation between DILPs, and these features may themselves be of evolutionary advantage. ..
  30. Teleman A, Chen Y, Cohen S. 4E-BP functions as a metabolic brake used under stress conditions but not during normal growth. Genes Dev. 2005;19:1844-8 pubmed
    ..We suggest that 4E-BP works as a metabolic brake that is activated under conditions of environmental stress to control fat metabolism. 4E-BP mutants lack this regulation, reducing their ability to survive under unfavorable conditions. ..
  31. Teleman A. Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem J. 2009;425:13-26 pubmed publisher
    ..I discuss both the intracellular signalling network, as well as the communication between organs in the fly. ..
  32. Agrawal N, Padmanabhan N, Hasan G. Inositol 1,4,5- trisphosphate receptor function in Drosophila insulin producing cells. PLoS ONE. 2009;4:e6652 pubmed publisher
    ..These data support a model where InsP(3)R activity in non-overlapping neuronal domains independently rescues larval itpr phenotypes by non-cell autonomous mechanisms. ..
  33. Puig O, Marr M, Ruhf M, Tjian R. Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev. 2003;17:2006-20 pubmed
    ..induces growth arrest and activates two key players of the dInR/dPI3K/dAkt pathway: the translational regulator d4EBP and the dInR itself...
  34. Miron M, Verdu J, Lachance P, Birnbaum M, Lasko P, Sonenberg N. The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila. Nat Cell Biol. 2001;3:596-601 pubmed
    ..Our results support a role for d4E-BP as an effector of cell growth. ..
  35. Teleman A, Chen Y, Cohen S. Drosophila Melted modulates FOXO and TOR activity. Dev Cell. 2005;9:271-81 pubmed
    ..We provide evidence that in the melted mutant, TOR activity is reduced and FOXO is activated. The melted mutant condition mimics the effects of nutrient deprivation in a normal animal, producing an animal with 40% less fat than normal. ..
  36. Tettweiler G, Miron M, Jenkins M, Sonenberg N, Lasko P. Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP. Genes Dev. 2005;19:1840-3 pubmed
    ..Thus, d4E-BP is an important downstream effector of a dFOXO phenotype, and regulation of translation by eIF4E is vital during environmental stress. ..
  37. Cheng L, Bailey A, Leevers S, Ragan T, Driscoll P, Gould A. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell. 2011;146:435-47 pubmed publisher
    ..Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors. ..
  38. Slack C, Giannakou M, Foley A, Goss M, Partridge L. dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Aging Cell. 2011;10:735-48 pubmed publisher
  39. Birse R, Choi J, Reardon K, Rodriguez J, Graham S, Diop S, et al. High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab. 2010;12:533-44 pubmed publisher
    ..Moreover, reducing insulin-TOR activity (by expressing TSC1-2, 4EBP or FOXO), or increasing lipase expression-only within the myocardium-suffices to efficiently alleviate cardiac fat ..
  40. Grewal S. Controlling animal growth and body size - does fruit fly physiology point the way?. F1000 Biol Rep. 2012;4:12 pubmed publisher
    ..While this concept is obviously not new, these fly studies now open up the possibility of using a genetically tractable system to dissect in detail how organ-to-organ communication dictates body size. ..
  41. Zid B, Rogers A, Katewa S, Vargas M, Kolipinski M, Lu T, et al. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell. 2009;139:149-60 pubmed publisher
    ..The translational repressor 4E-BP, the eukaryotic translation initiation factor 4E binding protein, was upregulated upon DR and mediated DR dependent changes in mitochondrial activity ..
  42. Wittwer F, Jaquenoud M, Brogiolo W, Zarske M, Wüstemann P, Fernandez R, et al. Susi, a negative regulator of Drosophila PI3-kinase. Dev Cell. 2005;8:817-27 pubmed
    ..The fact that Susi is expressed in a circadian rhythm, with highest levels during the night, suggests that Susi attenuates insulin signaling during the fasting period. ..
  43. Rera M, Clark R, Walker D. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A. 2012;109:21528-33 pubmed publisher
    ..Our findings suggest that intestinal barrier dysfunction may be an important factor in the pathophysiology of aging in other species as well, including humans. ..
  44. Hull Thompson J, Muffat J, Sanchez D, Walker D, Benzer S, Ganfornina M, et al. Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz. PLoS Genet. 2009;5:e1000460 pubmed publisher
    ..The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis. ..
  45. Delanoue R, Slaidina M, Leopold P. The steroid hormone ecdysone controls systemic growth by repressing dMyc function in Drosophila fat cells. Dev Cell. 2010;18:1012-21 pubmed publisher
    ..In conclusion, the present work reveals an unexpected function of dMyc in the systemic control of growth in response to steroid hormone signaling. ..
  46. Flatt T, Min K, D Alterio C, Villa Cuesta E, Cumbers J, Lehmann R, et al. Drosophila germ-line modulation of insulin signaling and lifespan. Proc Natl Acad Sci U S A. 2008;105:6368-73 pubmed publisher
    ..These results suggest that signals from the gonad regulate lifespan and modulate insulin sensitivity in the fly and that the gonadal regulation of aging is evolutionarily conserved. ..
  47. Buch S, Melcher C, Bauer M, Katzenberger J, Pankratz M. Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling. Cell Metab. 2008;7:321-32 pubmed publisher
    ..tobi is thus a target of the insulin- and glucagon-like signaling system that responds oppositely to dietary protein and sugar. ..
  48. Hall D, Grewal S, de la Cruz A, Edgar B. Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila. BMC Biol. 2007;5:10 pubmed
    ..The effect of insulin signaling upon TOR activity varies according to cellular type and context. ..
  49. Luong N, Davies C, Wessells R, Graham S, King M, Veech R, et al. Activated FOXO-mediated insulin resistance is blocked by reduction of TOR activity. Cell Metab. 2006;4:133-42 pubmed
    ..Thus, the regulation of dTOR activity may be an ancient "systems biological" means of regulating metabolism and senescence, that has important evolutionary, physiological, and clinical implications. ..
  50. Jünger M, Rintelen F, Stocker H, Wasserman J, Végh M, Radimerski T, et al. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol. 2003;2:20 pubmed
    ..We propose that in response to cellular stresses, such as nutrient deprivation or increased levels of reactive oxygen species, dFOXO is activated and inhibits growth through the action of target genes such as d4E-BP. ..
  51. Bjedov I, Toivonen J, Kerr F, Slack C, Jacobson J, Foley A, et al. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11:35-46 pubmed publisher
    ..Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms. ..
  52. Wang M, Bohmann D, Jasper H. JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell. 2005;121:115-25 pubmed
    ..The convergence of JNK signaling and IIS on Foxo provides a model to explain the effects of stress and nutrition on longevity. ..
  53. Huang H, Lu Bo Y, Haddad G. A Drosophila ABC transporter regulates lifespan. PLoS Genet. 2014;10:e1004844 pubmed publisher
  54. Tixier V, Bataillé L, Etard C, Jagla T, Weger M, Daponte J, et al. Glycolysis supports embryonic muscle growth by promoting myoblast fusion. Proc Natl Acad Sci U S A. 2013;110:18982-7 pubmed publisher