Rheb

Summary

Gene Symbol: Rheb
Description: Ras homolog enriched in brain
Alias: CG1081, DReb, Dm Rheb, DmRheb, Dmel\CG1081, Q9VND8, RHEB, RheB, dRheb, rheb, CG1081 gene product from transcript CG1081-RA, CG1081-PA, CG1081-PB, RAS homolog enriched in brain, Ras homolog enriched in brain ortholog, Ras homologue enriched in brain, Ras homology enriched in brain, Rheb-PA, Rheb-PB
Species: fruit fly

Top Publications

  1. pmc Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons
    James A Walker
    Massachusetts General Hospital Center for Cancer Research and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Genes Dev 20:3311-23. 2006
  2. doi Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb
    H Rehmann
    Department of Physiological Chemistry and Center for Biomedical Genetics, UMC Utrecht Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    FEBS Lett 582:3005-10. 2008
  3. pmc Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death
    Ryan C Scott
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Curr Biol 17:1-11. 2007
  4. pmc A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling
    Greg M Findlay
    Institute of Cancer Research, Cancer Research U K Centre of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, U K
    Biochem J 403:13-20. 2007
  5. ncbi Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase
    Ya Chieh Hsu
    Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nature 445:785-8. 2007
  6. pmc ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase
    Sung Bae Lee
    National Creative Research Initiatives Center for Cell Growth Regulation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Taejon 305 701, Republic of Korea
    EMBO Rep 8:360-5. 2007
  7. pmc Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila
    Dayna J Hall
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    BMC Biol 5:10. 2007
  8. pmc Mechanisms of TSC-mediated control of synapse assembly and axon guidance
    Sarah Knox
    The Developmental Biology Center, Department of Pediatrics, The University of Minnesota, Minneapolis, Minnesota, United States of America
    PLoS ONE 2:e375. 2007
  9. pmc Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway
    Savraj S Grewal
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    J Cell Biol 179:1105-13. 2007
  10. pmc FOXO-regulated transcription restricts overgrowth of Tsc mutant organs
    Kieran F Harvey
    Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia
    J Cell Biol 180:691-6. 2008

Scientific Experts

  • Kwang Wook Choi
  • Irene Papatheodorou
  • Emmanuel Taillebourg
  • Qi Wu
  • Tao Wang
  • Lutz Kockel
  • Savraj S Grewal
  • Carlos Ribeiro
  • John M Rawls
  • Sergey Nuzhdin
  • Paul Jorgensen
  • Kieran Harvey
  • Dayna J Hall
  • G Jekely
  • Mark Eddison
  • Deborah C I Goberdhan
  • Duojia Pan
  • Thomas P Neufeld
  • Bruce A Edgar
  • Gabor Juhasz
  • Helen McNeill
  • Tianyi Zhang
  • Joseph M Bateman
  • Wei Du
  • Gabriel M Gordon
  • Kun Liang Guan
  • Qian Yang
  • Ken Inoki
  • Ryan C Scott
  • Ya Chieh Hsu
  • Parthive H Patel
  • Thao Phuong Le
  • Iswar K Hariharan
  • Eunjung Kim
  • Joseph Parker
  • Naoki Okamoto
  • Michelle L Steinhilb
  • Rajaguru Aradhya
  • TingTing Gu
  • Hugo Stocker
  • Pierre Luc Bardet
  • JONATHAN ZIRIN
  • Consuelo Ibar
  • Fergal O'Farrell
  • Amelie Avet-Rochex
  • Brian Dimitroff
  • Karolina Pircs
  • Ching On Wong
  • Heather L D Brown
  • David Alvarez-Ponce
  • Norman Zielke
  • Louise Y Cheng
  • Hong Wen Tang
  • J M I Barth
  • Alex P Gould
  • Rita Sousa-Nunes
  • M Willecke
  • Martín Resnik-Docampo
  • Juan M Murillo-Maldonado
  • Federica Parisi
  • Ting Chiu Hsieh
  • I Nisoli
  • Brian S Robinson
  • Xiangzhong Zheng
  • Magdalena Karbowniczek
  • Binghui Li
  • Scott B Selleck
  • Leslie J Saucedo
  • MICHAEL B O'CONNOR
  • K Kohler
  • Rachel K Smith-Bolton
  • Kistie Patch
  • Joanna Doumanis
  • Yu Yun Chang
  • Hiroshi Kanda
  • Sophie Layalle
  • H Rehmann
  • Sung Bae Lee
  • Sarah Knox
  • Greg M Findlay
  • Ai Sun Kelly Tseng
  • Mel B Feany
  • Christian Mosimann
  • Vikram Khurana
  • James A Walker
  • Krista M Hennig
  • Héctor Herranz
  • Alfonso Martín-Peña
  • Sean Oldham
  • Anne Sustar

Detail Information

Publications87

  1. pmc Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons
    James A Walker
    Massachusetts General Hospital Center for Cancer Research and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Genes Dev 20:3311-23. 2006
    ....
  2. doi Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb
    H Rehmann
    Department of Physiological Chemistry and Center for Biomedical Genetics, UMC Utrecht Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    FEBS Lett 582:3005-10. 2008
    ..It has been postulated to serve as a guanine nucleotide exchange factor for the small G-protein Rheb. Rheb functions in the PI3 kinase/mTOR pathway...
  3. pmc Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death
    Ryan C Scott
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Curr Biol 17:1-11. 2007
    ..Here, we circumvent this difficulty by directly manipulating autophagy rates in Drosophila through the autophagy-specific protein kinase Atg1...
  4. pmc A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling
    Greg M Findlay
    Institute of Cancer Research, Cancer Research U K Centre of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, U K
    Biochem J 403:13-20. 2007
    ..Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3...
  5. ncbi Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase
    Ya Chieh Hsu
    Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nature 445:785-8. 2007
    ..Activation of the TSC pathway is mediated by Rheb (Ras homologue enriched in brain), a Ras superfamily GTPase...
  6. pmc ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase
    Sung Bae Lee
    National Creative Research Initiatives Center for Cell Growth Regulation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Taejon 305 701, Republic of Korea
    EMBO Rep 8:360-5. 2007
    ..Taken together, our genetic and biochemical results strongly indicate crosstalk between autophagy and cell growth regulation...
  7. pmc Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila
    Dayna J Hall
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    BMC Biol 5:10. 2007
    The Ras-related GTPase, Rheb, regulates the growth of animal cells...
  8. pmc Mechanisms of TSC-mediated control of synapse assembly and axon guidance
    Sarah Knox
    The Developmental Biology Center, Department of Pediatrics, The University of Minnesota, Minneapolis, Minnesota, United States of America
    PLoS ONE 2:e375. 2007
    ..Mutations in TSC1 or TSC2 deregulate a conserved growth control pathway that includes Ras homolog enriched in brain (Rheb) and Target of Rapamycin (TOR)...
  9. pmc Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway
    Savraj S Grewal
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    J Cell Biol 179:1105-13. 2007
    ..Stimulation of rRNA synthesis by TIF-IA may therefore provide a feed-forward mechanism to coregulate the levels of other ribosome components...
  10. pmc FOXO-regulated transcription restricts overgrowth of Tsc mutant organs
    Kieran F Harvey
    Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia
    J Cell Biol 180:691-6. 2008
    ..Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species...
  11. pmc The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila
    Gabor Juhasz
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
    J Cell Biol 181:655-66. 2008
    ..Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation...
  12. pmc Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin pathway in Drosophila
    Helen McNeill
    The Wolfson Centre for Age Related Diseases, King s College, London SE1 1UL, United Kingdom
    Genetics 179:843-53. 2008
    ..Together these data suggest that InR/TOR signaling regulates the timing of differentiation through modulation of EGFR target genes in developing photoreceptors...
  13. pmc Regulation of TORC1 by Rag GTPases in nutrient response
    Eunjung Kim
    Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093 081, USA
    Nat Cell Biol 10:935-45. 2008
    ..Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals...
  14. ncbi Rheb is an essential regulator of S6K in controlling cell growth in Drosophila
    Hugo Stocker
    Zoologisches Institut der Universitat Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
    Nat Cell Biol 5:559-65. 2003
    ..Here we describe a new effector in growth control, the small GTPase Rheb (Ras homologue enriched in brain)...
  15. pmc An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation
    Yu Yun Chang
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA
    Mol Biol Cell 20:2004-14. 2009
    ..Atg1-Atg13 complexes thus function at multiple levels to mediate and adjust nutrient-dependent autophagic signaling...
  16. pmc TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease
    Tao Wang
    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    J Cell Biol 186:703-11. 2009
    ..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...
  17. pmc The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous sclerosis complex and Drosophila external sensory organ development
    Magdalena Karbowniczek
    Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
    J Clin Invest 120:93-102. 2010
    ..We report here that inactivation of Tsc1 and overexpression of the Ras homolog Rheb each resulted in duplication of the bristle and socket cells, progeny of the pIIa cell, and loss of the neuronal ..
  18. pmc Specific killing of Rb mutant cancer cells by inactivating TSC2
    Binghui Li
    Ben May Department for Cancer Research, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
    Cancer Cell 17:469-80. 2010
    ..Inactivation of TSC2 and Rb synergistically induce oxidative stress via increased protein synthesis, inhibited de novo lipid synthesis, and decreased reactive oxygen species scavenger enzyme SOD2 induction...
  19. pmc Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling
    Lutz Kockel
    Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Genet 6:e1000990. 2010
    ..These results illustrate how the Akt-TOR pathway dynamically adapts the routing of negative feedback in response to the activity load of its signaling circuit in vivo...
  20. pmc Tuberous sclerosis complex 1 regulates dE2F1 expression during development and cooperates with RBF1 to control proliferation and survival
    Ting Chiu Hsieh
    Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Canada
    PLoS Genet 6:e1001071. 2010
    ..revealed that the protein level of dE2F1 is increased in tsc1 or tsc2 mutant cells and conversely decreased in rheb or dTor mutant cells...
  21. pmc Autophagy in Drosophila ovaries is induced by starvation and is required for oogenesis
    J M I Barth
    Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
    Cell Death Differ 18:915-24. 2011
    ..Our data establish an important function for autophagy during oogenesis and contributes to the understanding of the role of autophagy in animal development...
  22. pmc Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila
    Rita Sousa-Nunes
    Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Nature 471:508-12. 2011
    ..This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour...
  23. doi Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila
    Louise Y Cheng
    Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
    Cell 146:435-47. 2011
    ..First, Alk suppresses the growth requirement for amino acid sensing via Slimfast/Rheb/TOR complex 1. And second, Alk, rather than insulin-like receptor, primarily activates PI3-kinase...
  24. pmc Control of Drosophila endocycles by E2F and CRL4(CDT2)
    Norman Zielke
    German Cancer Research Center DKFZ Zentrum für Molekulare Biologie der Universität Heidelberg Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
    Nature 480:123-7. 2011
    ..Many of the regulatory interactions essential to this novel cell cycle oscillator are conserved in animals and plants, indicating that elements of this mechanism act in most growth-dependent cell cycles...
  25. pmc The small GTPase Rheb affects central brain neuronal morphology and memory formation in Drosophila
    Heather L D Brown
    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
    PLoS ONE 7:e44888. 2012
    ..We overexpressed Rheb, an upstream regulator of TOR, in two different subsets of D...
  26. pmc Deregulated G1-S control and energy stress contribute to the synthetic-lethal interactions between inactivation of RB and TSC1 or TSC2
    Gabriel M Gordon
    Ben May Department for Cancer Research, The University of Chicago, 929 E 57th Street, Chicago, IL 60637, USA
    J Cell Sci 126:2004-13. 2013
    ..cell death in tissues that have lost the RB and TSC orthologs rbf and dtsc1/gig, respectively, or overexpress Rheb and dE2F1, are correlated with synergistic defects in G1-S control, which causes cells to accumulate DNA damage...
  27. ncbi The Saccharomyces cerevisiae Rheb G-protein is involved in regulating canavanine resistance and arginine uptake
    J Urano
    Department of Microbiology, Molecular Biology Institute, University of California, Los Angeles, California 90095 1489, USA
    J Biol Chem 275:11198-206. 2000
    The new member of the Ras superfamily of G-proteins, Rheb, has been identified in rat and human, but its function has not been defined...
  28. ncbi Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing
    Tânia Reis
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Cell 117:253-64. 2004
    ..g., by ectopic Dacapo, dWee1, dMyc, or Rheb)...
  29. ncbi Tuberous sclerosis complex: from Drosophila to human disease
    Duojia Pan
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9040, USA
    Trends Cell Biol 14:78-85. 2004
    ..and mammalian cells demonstrate that the TSC1-TSC2 complex functions as GTPase activating protein against Rheb - a Ras-like small GTPase, which in turn regulates TOR signaling in nutrient-stimulated cell growth...
  30. ncbi Rheb fills a GAP between TSC and TOR
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Rm 1028, 4 Blackfan Circle, Boston, MA 02115, USA
    Trends Biochem Sci 28:573-6. 2003
    ..these genetic, biochemical and cell-biological studies have demonstrated that the tuberin-hamartin complex inhibits target of rapamycin (TOR) signaling by acting as a GTPase-activating protein for the Ras-related small G protein Rheb.
  31. ncbi Role and regulation of starvation-induced autophagy in the Drosophila fat body
    Ryan C Scott
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis 55455 USA
    Dev Cell 7:167-78. 2004
    ..Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the Drosophila fat body...
  32. ncbi Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins
    Yong Zhang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9040, USA
    Nat Cell Biol 5:578-81. 2003
    ..Here we show that the small GTPase Rheb (Ras homologue enriched in brain) is a direct target of Tsc2 GAP activity both in vivo and in vitro...
  33. ncbi Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila
    Joseph M Bateman
    Cancer Research UK, 44 Lincoln s Inn Fields, London, WC2A 3PX, England
    Cell 119:87-96. 2004
    ..Examination of InR, PI3K, PTEN, Tor, Rheb, and S6 kinase mutants demonstrates that increased InR signaling leads to precocious differentiation while ..
  34. ncbi Rheb promotes cell growth as a component of the insulin/TOR signalling network
    Leslie J Saucedo
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Nat Cell Biol 5:566-71. 2003
    ..In a screen for novel regulators of growth, we identified Rheb (Ras homologue enriched in brain), a member of the Ras superfamily of GTP-binding proteins...
  35. pmc The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila
    Jan H Reiling
    Zoologisches Institut, Universitat Zurich, CH 8057 Zurich, Switzerland
    Genes Dev 18:2879-92. 2004
    ....
  36. ncbi PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids
    Deborah C I Goberdhan
    Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK
    Development 132:2365-75. 2005
    ..As PATH is likely to be saturated in vivo, we propose that one specialised function of high-affinity PAT-related molecules is to maintain growth as local nutrient levels fluctuate during development...
  37. ncbi The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in Drosophila by promoting nuclear localization of HIF-alpha/Sima
    Andres Dekanty
    Instituto Leloir and IIB, FCEyN Universidad de Buenos Aires, CONICET, Patricias Argentinas 435, Buenos Aires 1405, Argentina
    J Cell Sci 118:5431-41. 2005
    ..We conclude that regulation of HIF-alpha/Sima by the PI3K-AKT-TOR pathway is a major conserved mode of regulation of the HIF-dependent transcriptional response in Drosophila...
  38. pmc TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity
    Qian Yang
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 103:6811-6. 2006
    ..The Ras homology enriched in brain (Rheb) small GTPase is known to be a key upstream activator of TORC1, although the mechanism of Rheb ..
  39. ncbi Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress
    Parthive H Patel
    Molecular Biology Institute, Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095 1489, USA
    J Cell Sci 119:4285-92. 2006
    ..The well-conserved Rheb-Target-of-rapamycin (TOR)-S6-kinase (S6K) signaling pathway regulates several cellular processes and has been shown ..
  40. ncbi Age-independent synaptogenesis by phosphoinositide 3 kinase
    Alfonso Martín-Peña
    Cajal Institute, Consejo Superior de Investigaciones Cientificas, 28002 Madrid, Spain
    J Neurosci 26:10199-208. 2006
    ..Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders...
  41. pmc TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth
    Krista M Hennig
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
    J Cell Biol 173:963-74. 2006
    ..Our data indicate that endocytosis acts both as an effector function downstream of TOR and as a physiologically relevant regulator of TOR signaling...
  42. ncbi Drosophila Rheb GTPase is required for cell cycle progression and cell growth
    Parthive H Patel
    Molecular Biology Institute, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095 1489, USA
    J Cell Sci 116:3601-10. 2003
    ..a screen to identify genes affecting hindgut morphogenesis in Drosophila, we identified a P-element insertion in dRheb, a novel, highly conserved member of the Ras superfamily of G-proteins...
  43. pmc 14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila
    Thao Phuong Le
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak ro, Yuseong Gu, Daejeon 305 701, Korea
    Nat Commun 7:11501. 2016
    ..two interacting components of Tor signalling in Drosophila, translationally controlled tumour protein (Tctp) and Rheb GTPase...
  44. doi Drosophila p53-related protein kinase is required for PI3K/TOR pathway-dependent growth
    Consuelo Ibar
    FONDAP Center for Genome Regulation, Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Santiago, Chile
    Development 140:1282-91. 2013
    ..This suggests that Prpk is crucial for stimulating the basal protein biosynthetic machinery in response to insulin signaling and to changes in nutrient availability...
  45. pmc Hyperactivated Wnt signaling induces synthetic lethal interaction with Rb inactivation by elevating TORC1 activities
    Tianyi Zhang
    Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois, United States of America
    PLoS Genet 10:e1004357. 2014
    ..These results suggest that elevated TORC1 activity and metabolic stress underpin the evolutionarily conserved synthetic lethal interaction between hyperactivated Wnt signaling and inactivated Rb tumor suppressor. ..
  46. pmc Scaling the Drosophila Wing: TOR-Dependent Target Gene Access by the Hippo Pathway Transducer Yorkie
    Joseph Parker
    Department of Genetics and Development, Columbia University, New York, New York, United States of America Division of Biology, Imperial College London, London, United Kingdom
    PLoS Biol 13:e1002274. 2015
    ....
  47. pmc Drosophila TRPML is required for TORC1 activation
    Ching On Wong
    Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, Houston, TX 77030, USA
    Curr Biol 22:1616-21. 2012
    ..Our findings delineate the interrelationship between the TRPML and TORC1 pathways and raise the intriguing possibility that a high-protein diet might reduce the severity of MLIV...
  48. doi The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins
    Emmanuel Taillebourg
    CEA Institut de Recherches en Technologies et Sciences pour le Vivant, Laboratoire de Biologie à Grande Echelle, Grenoble, France
    Autophagy 8:767-79. 2012
    ..Importantly, USP36 function in p62-dependent selective autophagy is conserved in human cells. Our work identifies a novel, crucial role for a deubiquitinating enzyme in selective autophagy...
  49. pmc Two-tiered control of epithelial growth and autophagy by the insulin receptor and the ret-like receptor, stitcher
    Fergal O'Farrell
    Department of Molecular Biosciences, The Wenner Gren Institute, Stockholm University, Stockholm, Sweden
    PLoS Biol 11:e1001612. 2013
    ..The combined activities of Stit and InR in ectodermal epithelial tissues provide an RTK-mediated, two-tiered reaction threshold to varying nutritional conditions that promote epithelial organ growth even at low levels of InR signaling. ..
  50. doi Signaling from Glia and Cholinergic Neurons Controls Nutrient-Dependent Production of an Insulin-like Peptide for Drosophila Body Growth
    Naoki Okamoto
    Laboratory for Growth Control Signaling, RIKEN Center for Developmental Biology CDB, 2 2 3 Minatojima minamimachi, Chuo Ku, Kobe, Hyogo 650 0047, Japan
    Dev Cell 35:295-310. 2015
    ..These results provide a molecular framework that explains how the production of an endocrine hormone in a specific tissue is coordinated with environmental conditions. ..
  51. pmc Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila
    Rajaguru Aradhya
    Génétique Reproduction et Développement, INSERM U1103, CNRS UMR6293, Clermont Ferrand, France
    elife 4:. 2015
    ..Altogether, we report that Drosophila AMPs display homing behavior to muscle niche and that the niche-driven Insulin-Notch-dMyc cascade plays a key role in setting the activated state of AMPs. ..
  52. doi Loss of PI3K blocks cell-cycle progression in a Drosophila tumor model
    M Willecke
    Institute of Molecular Life Sciences, University of Zurich, Switzerland
    Oncogene 30:4067-74. 2011
    ..The results presented here broaden our insights into the intricate mechanisms underling tumorigenesis and illustrate the power of Drosophila genetics in revealing weak points of tumor progression...
  53. pmc Drosophila insulin pathway mutants affect visual physiology and brain function besides growth, lipid, and carbohydrate metabolism
    Juan M Murillo-Maldonado
    Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
    Diabetes 60:1632-6. 2011
    ..Given this problem, genetic model systems, such as in flies where type 2 diabetes can be modeled and studied, offer distinct advantages...
  54. pmc MAP4K3 is a component of the TORC1 signalling complex that modulates cell growth and viability in Drosophila melanogaster
    Martín Resnik-Docampo
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas and Universidad Autonoma de Madrid, Madrid, Spain
    PLoS ONE 6:e14528. 2011
    ..We have analyzed the consequences of changing the levels of MAP4K3 expression in the development of the Drosophila wing, a convenient model system to characterize gene function during epithelial development...
  55. doi PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue
    Pierre Luc Bardet
    Polarity Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Dev Cell 25:534-46. 2013
    ....
  56. pmc Insulin signaling regulates neurite growth during metamorphic neuronal remodeling
    TingTing Gu
    Department of Biology, University of Oklahoma, Norman, OK 73019, USA
    Biol Open 3:81-93. 2014
    ..In contrast, expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1, Rheb, and TOR, as well as RNA interference for negative regulators of insulin signaling (PTEN, FOXO), stimulated ..
  57. pmc Role of autophagy in glycogen breakdown and its relevance to chloroquine myopathy
    JONATHAN ZIRIN
    Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Biol 11:e1001708. 2013
    ....
  58. pmc Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy
    Hong Wen Tang
    Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    EMBO J 30:636-51. 2011
    ..Our findings provide evidence of a link between Atg1 and the control of Atg9-mediated autophagosome formation through the myosin II motor protein...
  59. pmc Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila
    Karolina Pircs
    Department of Anatomy, Cell and Developmental Biology, Eotvos Lorand University, Budapest, Hungary
    PLoS ONE 7:e44214. 2012
    ....
  60. doi Neurodegeneration by polyglutamine Atrophin is not rescued by induction of autophagy
    I Nisoli
    Dulbecco Telethon Institute and Division of Neuroscience, DIBIT San Raffaele Scientific Institute, Via Olgettina 58, Milan I 20132, Italy
    Cell Death Differ 17:1577-87. 2010
    ..Our data thus provide a crucial insight into the specific mechanism of a polyglutamine disease and reveal important differences in the role of autophagy with respect to other diseases of the same family...
  61. doi arouser reveals a role for synapse number in the regulation of ethanol sensitivity
    Mark Eddison
    Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA
    Neuron 70:979-90. 2011
    ..We thus show that a developmental abnormality affecting synapse number and ethanol sensitivity is not permanent and can be reversed by manipulating the environment of the adult fly...
  62. doi Molecular population genetics of the insulin/TOR signal transduction pathway: a network-level analysis in Drosophila melanogaster
    David Alvarez-Ponce
    Departament de Genetica, i Institut de Recerca de la Biodiversitat, Universitat de Barcelona, Barcelona, Spain
    Mol Biol Evol 29:123-32. 2012
    ..The detected polarity would be, therefore, intrinsic to the IT pathway architecture and function...
  63. pmc Concerted control of gliogenesis by InR/TOR and FGF signalling in the Drosophila post-embryonic brain
    Amelie Avet-Rochex
    Wolfson Centre for Age Related Diseases, King s College London, Guy s Campus, London, UK
    Development 139:2763-72. 2012
    ..In summary, we have identified two major pathways that control perineural and cortex gliogenesis in the post-embryonic brain and have shown that the molecular circuitry required is lineage specific...
  64. pmc Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo
    Federica Parisi
    Department of Biology, City College of City University of New York, New York, USA
    BMC Biol 9:65. 2011
    ..Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways...
  65. pmc Diet and energy-sensing inputs affect TorC1-mediated axon misrouting but not TorC2-directed synapse growth in a Drosophila model of tuberous sclerosis
    Brian Dimitroff
    Department of Genetics, Cell Biology and Development, Developmental Biology Center, University of Minnesota, Minneapolis, Minnesota, United States of America
    PLoS ONE 7:e30722. 2012
    ..In Drosophila, neuron-specific overexpression of Rheb, the direct downstream target inhibited by Tsc1/Tsc2, produced significant synapse overgrowth, axon misrouting, and ..
  66. pmc LST8 regulates cell growth via target-of-rapamycin complex 2 (TORC2)
    Tao Wang
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Mol Cell Biol 32:2203-13. 2012
    ..In mutants lacking LST8, expression of TOR and RAPTOR, together with their upstream activator Rheb, was sufficient to provide TORC1 activity and stimulate cell and organ growth...
  67. ncbi How cells coordinate growth and division
    Paul Jorgensen
    Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON, Canada M5S 1A8
    Curr Biol 14:R1014-27. 2004
    ..Recently, genetic screens in Drosophila and functional genomics approaches in yeast have macheted into the thicket of cell size control...
  68. pmc Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity
    Qian Yang
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    Genes Dev 20:2820-32. 2006
    ..These data demonstrate that Sin1 together with Rictor are key components of mTORC2 and play an essential role in Akt phosphorylation and signaling...
  69. ncbi A transient cell cycle shift in Drosophila imaginal disc cells precedes multipotency
    Anne Sustar
    Department of Biology, University of Washington, Seattle, Washington 98195, USA
    Cell 120:383-93. 2005
    ..We propose that it is not a younger but a unique cell cycle progression and a big cell size that conditions the cells for developmental plasticity...
  70. pmc Analysis of pyrimidine catabolism in Drosophila melanogaster using epistatic interactions with mutations of pyrimidine biosynthesis and beta-alanine metabolism
    John M Rawls
    Molecular and Cellular Biology Group, Department of Biology, University of Kentucky, Lexington, Kentucky 40506, USA
    Genetics 172:1665-74. 2006
    ..These results are discussed in the context of similar consequences of 5-fluoropyrimidine toxicity and pyrimidine catabolism mutations in humans...
  71. ncbi TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model
    Vikram Khurana
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Harvard New Research Building Room 652, 77 Louis Pasteur Avenue, Boston, Massachusetts 02115, USA
    Curr Biol 16:230-41. 2006
    ..However, the critical questions of whether cell-cycle activation is causal or epiphenomenal to tau-induced neurodegeneration and which signaling pathways mediate cell-cycle activation in tauopathy remain unresolved...
  72. pmc Tau phosphorylation sites work in concert to promote neurotoxicity in vivo
    Michelle L Steinhilb
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Mol Biol Cell 18:5060-8. 2007
    ..These findings suggest that serine-proline/threonine-proline sites cooperate to mediate neurodegeneration in vivo...
  73. ncbi Complexity of the TOR signaling network
    Ken Inoki
    Life Sciences Institute, Department of Biological Chemistry, Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109, USA
    Trends Cell Biol 16:206-12. 2006
    ..Here, we discuss new findings that have extended the complexity of TOR signaling and the different roles of the TORC complexes in yeast, flies and mammals...
  74. pmc Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/ras signaling pathway
    Ai Sun Kelly Tseng
    Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA
    Curr Biol 17:728-33. 2007
    ..Thus, the DNA-binding protein Cic is a key downstream component in the pathway by which Ras regulates growth in imaginal discs...
  75. ncbi Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo
    Christian Mosimann
    National Research Center Frontiers in Genetics, Institut fur Molekularbiologie, Universitat Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
    Cell 125:327-41. 2006
    ....
  76. ncbi calderón encodes an organic cation transporter of the major facilitator superfamily required for cell growth and proliferation of Drosophila tissues
    Héctor Herranz
    ICREA and Institut de Recerca Biomedica, Parc Cientific de Barcelona, Josep Samitier, 1 5, 08028 Barcelona, Spain
    Development 133:2617-25. 2006
    ..Our results indicate that growth of imaginal cells may be modulated by two distinct, but coordinated, nutrient-sensing mechanisms: one cell-autonomous and the other humoral...
  77. pmc AKT and TOR signaling set the pace of the circadian pacemaker
    Xiangzhong Zheng
    Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Curr Biol 20:1203-8. 2010
    ....
  78. doi The TOR pathway couples nutrition and developmental timing in Drosophila
    Sophie Layalle
    IBDC, University of Nice Sophia Antipolis, CNRS, Parc Valrose, 06108 Nice, France
    Dev Cell 15:568-77. 2008
    ..In conclusion, the PG uses TOR signaling to couple nutritional input with ecdysone production and developmental timing...
  79. pmc To cease or to proliferate: new insights into TCTP function from a Drosophila study
    Kwang Wook Choi
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell Adh Migr 1:129-30. 2007
    ..1) Rheb (Ras homolog enriched in brain) is a small GTPase in the Tor pathway...
  80. pmc Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster
    Sergey V Nuzhdin
    Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
    BMC Genomics 10:124. 2009
    ..We focus on the latter problem by describing genetic variation in transcript levels of genes in the InR/TOR pathway among 72 Drosophila melanogaster genotypes...
  81. pmc Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc
    Rachel K Smith-Bolton
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Dev Cell 16:797-809. 2009
    ..This system is conducive to forward genetic screens, enabling an unbiased search for genes that regulate both the extent of and the capacity for regeneration...
  82. pmc RNAi screening in Drosophila cells identifies new modifiers of mutant huntingtin aggregation
    Joanna Doumanis
    Lab for Structural Neuropathology, RIKEN Brain Science Institute, Wako, Saitama, Japan
    PLoS ONE 4:e7275. 2009
    ..Newly identified modifiers including genes related to nuclear transport, nucleotide processes, and signaling, may be involved in polyglutamine aggregate formation and Huntington disease cascades...
  83. pmc A second-site noncomplementation screen for modifiers of Rho1 signaling during imaginal disc morphogenesis in Drosophila
    Kistie Patch
    Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA
    PLoS ONE 4:e7574. 2009
    ....
  84. pmc Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded
    Brian S Robinson
    Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Curr Biol 20:582-90. 2010
    ....
  85. ncbi Small GTPases and the evolution of the eukaryotic cell
    Gaspar Jekely
    European Molecular Biology Laboratory, Developmental Biology, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Bioessays 25:1129-38. 2003
    ..Based on the reconstruction of putative roles for ancestral small GTPases, a hypothetical scenario on the origins of the first endomembranes, the nucleus, and phagocytosis is presented...
  86. doi Sex peptide receptor and neuronal TOR/S6K signaling modulate nutrient balancing in Drosophila
    Carlos Ribeiro
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Curr Biol 20:1000-5. 2010
    ..We propose that the brain uses these internal states to assign value to external sensory information from potential food sources, thereby guiding food choice and ensuring nutrient homeostasis...
  87. pmc Identification of an evolutionarily divergent U11 small nuclear ribonucleoprotein particle in Drosophila
    Claudia Schneider
    Department of Cellular Biochemistry, Max Planck Institute of Biophysical Chemistry, 37077 Goettingen, Germany
    Proc Natl Acad Sci U S A 101:9584-9. 2004
    ..A comparison of U11 snRNAs that we have identified from vertebrates, plants, and insects, suggests that an evolutionarily divergent U11 snRNA may be unique to Drosophila and not characteristic of insects in general...

Research Grants3

  1. QUANTITATIVE TRAIT LOCI RELATED TO DROSOPHILA SPECIATION
    Sergey Nuzhdin; Fiscal Year: 2004
    ..This comprehensive assessment of the genetics of several traits will further our understanding of the genetics of speciation. ..
  2. ORGANIZATION OF APICAL CELL JUNCTIONS IN EYE
    Kwang Wook Choi; Fiscal Year: 2005
    ..Therefore, studies on novel interaction of Crb and Par complexes will provide important insights into the mechanism of human CRB 1 in normal retinal development and diseases associated with CRB1 mutations. ..
  3. Nucleotide polymorphisms responsible for expression variation in Drosophila
    Sergey Nuzhdin; Fiscal Year: 2009
    ..These studies will contribute to building a pathway-minded description of complex character variation. They will shed light on the genetic architecture of transcript level variation in nature. ..