Tsc1

Summary

Gene Symbol: Tsc1
Description: CG6147 gene product from transcript CG6147-RA
Alias: CG6147, Dmel\CG6147, TSC, TSC1, dTSC, dTSC-1, dTSC1, dTsc1, dtsc1, rocky, tsc1, CG6147 gene product from transcript CG6147-RA, CG6147-PA, TTuberous sclerosis complex 1, Tsc1-PA, hamartin, jolly green giant, rocky, tuberous sclerosis 1, tuberous sclerosis complex 1, tuberous sclerosis complex protein 1
Species: fruit fly

Top Publications

  1. doi TSC1/2 tumour suppressor complex maintains Drosophila germline stem cells by preventing differentiation
    Pei Sun
    Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
    Development 137:2461-9. 2010
  2. 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
  3. 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
  4. pmc Tsc2 is not a critical target of Akt during normal Drosophila development
    Jixin Dong
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9040, USA
    Genes Dev 18:2479-84. 2004
  5. 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
  6. 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
  7. 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
  8. ncbi Drosophila Melted modulates FOXO and TOR activity
    Aurelio A Teleman
    Dev Cell 9:271-81. 2005
  9. pmc Drosophila target of rapamycin kinase functions as a multimer
    Yong Zhang
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Genetics 172:355-62. 2006
  10. ncbi JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila
    J H Lee
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong, Taejon, Korea
    Cell Death Differ 13:1110-22. 2006

Scientific Experts

Detail Information

Publications94

  1. doi TSC1/2 tumour suppressor complex maintains Drosophila germline stem cells by preventing differentiation
    Pei Sun
    Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
    Development 137:2461-9. 2010
    Tuberous sclerosis complex human disease gene products TSC1 and TSC2 form a functional complex that negatively regulates target of rapamycin (TOR), an evolutionarily conserved kinase that plays a central role in cell growth and metabolism...
  2. 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
    ..Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor...
  3. 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
    ..In a screen for patterning mutants, we isolated alleles of tsc1, a component of the insulin receptor (InR) growth control pathway...
  4. pmc Tsc2 is not a critical target of Akt during normal Drosophila development
    Jixin Dong
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9040, USA
    Genes Dev 18:2479-84. 2004
    ..Strikingly, such mutants completely rescue the lethality and cell growth defects of Tsc2-null mutants. Taken together, our data suggest that Tsc2 is not a critical substrate of Akt in normal Drosophila development...
  5. 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
    ..Together, genetic and biochemical analysis places Scylla/Charybdis downstream of PKB and upstream of TSC. Furthermore, we show that scylla and charybdis are induced under hypoxic conditions and that scylla is a target of ..
  6. 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...
  7. 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...
  8. ncbi Drosophila Melted modulates FOXO and TOR activity
    Aurelio A Teleman
    Dev Cell 9:271-81. 2005
    ..Here, we identify Melted as a new modulator of this pathway in Drosophila. Melted interacts with both Tsc1 and FOXO and can recruit these proteins to the cell membrane...
  9. pmc Drosophila target of rapamycin kinase functions as a multimer
    Yong Zhang
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Genetics 172:355-62. 2006
    ..mutations in the HEAT and kinase domains can dominantly interfere with wild-type TOR function in cells lacking TSC1 or TSC2...
  10. ncbi JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila
    J H Lee
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong, Taejon, Korea
    Cell Death Differ 13:1110-22. 2006
    ..Collectively, our studies unprecedentedly elucidate JNK as the downstream mediator of the LKB1-dependent apoptosis, and provide a new paradigm for understanding the diverse LKB1 functions in vivo...
  11. 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
    ..Here, we report that Tuberous Sclerosis Complex 1 (TSC1), a well-established tumor suppressor that regulates cell size, is an important regulator of ..
  12. 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...
  13. 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
    ..Furthermore, tuberous sclerosis complex 1 (TSC1) and TSC2, which are negative regulators of Rheb, have negative and positive effects on TORC1 and ..
  14. 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...
  15. ncbi The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation
    N Tapon
    Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
    Cell 105:345-55. 2001
    ..inherited human disease tuberous sclerosis, characterized by hamartomatous tumors, results from mutations in either TSC1 or TSC2. We have characterized mutations in the Drosophila Tsc1 and Tsc2/gigas genes...
  16. pmc Specific roles of Target of rapamycin in the control of stem cells and their progeny in the Drosophila ovary
    Leesa LaFever
    Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Development 137:2117-26. 2010
    ..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...
  17. pmc A Drosophila insulin-like peptide promotes growth during nonfeeding states
    Maija Slaidina
    Institute for Developmental Biology and Cancer, University of Nice Sophia Antipolis Centre National de la Recherche Scientifique, Parc Valrose, 06108 Nice, France
    Dev Cell 17:874-84. 2009
    ..This study reveals a specific class of ILPs induced upon metabolic stress that promotes growth in conditions of nutritional deprivation or following developmentally induced cessation of feeding...
  18. 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
    Mutations in either of the genes encoding the tuberous sclerosis complex (TSC), TSC1 and TSC2, result in a multisystem tumor disorder characterized by lesions with unusual lineage expression patterns...
  19. 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...
  20. 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
    ..Tuberous sclerosis (TSC) is a benign tumour syndrome caused by mutations in either TSC1 or TSC2 tumour suppressor genes...
  21. pmc Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth
    Ville Hietakangas
    European Molecular Biology Laboratory Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Genes Dev 21:632-7. 2007
    ..Thus, TORC2 acts as a rheostat to broaden the range of AKT signaling at the high end of its range...
  22. doi Molecular mechanisms of metabolic regulation by insulin in Drosophila
    Aurelio A Teleman
    German Cancer Research Center Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
    Biochem J 425:13-26. 2009
    ..I discuss both the intracellular signalling network, as well as the communication between organs in the fly...
  23. doi Remote control of insulin secretion by fat cells in Drosophila
    Charles Geminard
    Institute for Developmental Biology and Cancer, CNRS University of Nice Sophia Antipolis, Parc Valrose, 06108 Nice, France
    Cell Metab 10:199-207. 2009
    ..Thus, the availability of nutrients is remotely sensed in fat body cells and conveyed to the brain IPCs by a humoral signal controlling ILP release...
  24. 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
    ..Here, we further characterize this phenomenon. We show that tuberous sclerosis complex 1 mutations cause increased FOXO levels, resulting in elevated expression of FOXO-regulated genes, some ..
  25. pmc Akt phosphorylates both Tsc1 and Tsc2 in Drosophila, but neither phosphorylation is required for normal animal growth
    Sibylle Schleich
    German Cancer Research Center DKFZ, Heidelberg, Germany
    PLoS ONE 4:e6305. 2009
    ..Since Drosophila Tsc1, the obligate partner of Tsc2, has an Akt phosphorylation motif that is not conserved in mammals, we investigate ..
  26. 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...
  27. 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...
  28. pmc Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila
    Fabio Demontis
    Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Development 136:983-93. 2009
    ..Thus, maximal dMyc transcriptional activity depends on InR to control muscle mass, which in turn induces a systemic behavioral response to allocate body size and proportions...
  29. pmc Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway
    Pankaj Kapahi
    Division of Biology 156 29, California Institute of Technology, Pasadena, CA 91125, USA
    Curr Biol 14:885-90. 2004
    ..We find that overexpression of dTsc1, dTsc2, or dominant-negative forms of dTOR or dS6K all cause lifespan extension...
  30. 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
    ..Here, we show that synergistic 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 ..
  31. ncbi Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling
    Xinsheng Gao
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9040, USA
    Nat Cell Biol 4:699-704. 2002
    ..Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour suppressors that are responsible for the tuberous sclerosis syndrome, antagonize ..
  32. pmc Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling
    Thomas Radimerski
    Friedrich Miescher Institute for Biomedical Research, CH 4058, Basel, Switzerland
    Genes Dev 16:2627-32. 2002
    ..More importantly, we demonstrate that reducing dS6K signaling rescues early larval lethality associated with loss of dTsc1/2 function, arguing that the S6K pathway is a promising target for the treatment of TSC.
  33. pmc TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth
    X Gao
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9040, USA
    Genes Dev 15:1383-92. 2001
    Tuberous sclerosis is a human disease caused by mutations in the TSC1 or the TSC2 tumor suppressor gene...
  34. ncbi Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control
    Sean Oldham
    The Burnham Institute, La Jolla, CA 92037, USA
    Trends Cell Biol 13:79-85. 2003
    ..This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth...
  35. ncbi gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle
    N Ito
    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720 3200, USA
    Cell 96:529-39. 1999
    ..Our results suggest that the TSC disorder may result from an underlying defect in cell cycle control. We have also identified a Drosophila homolog of TSC1.
  36. 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
    ..Our genetic and biochemical analyses suggest that Rheb functions downstream of the tumour suppressors Tsc1 (tuberous sclerosis 1)-Tsc2 in the TOR (target of rapamycin) signalling pathway to control growth, and that a major effector of ..
  37. 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
    ..Recent studies suggest that the tuberous sclerosis complex Tsc1-Tsc2 may couple insulin signalling to Tor activity [corrected]...
  38. 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
    Mutations in the TSC1 or TSC2 genes cause tuberous sclerosis, a benign tumour syndrome in humans...
  39. pmc Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila
    Lynne Marshall
    Department of Biochemistry and Molecular Biology, Clark H Smith Brain Tumour Centre, Southern Alberta Cancer Research Institute, University of Calgary, HRIC, Calgary, Alberta, Canada
    EMBO J 31:1916-30. 2012
    ..Thus, stimulation of Pol III is a key downstream effector of TOR in the control of cellular and systemic growth...
  40. pmc The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling
    Martin A Jünger
    Zoologisches Institut, Universitat Zurich, Winterthurerstr, 190, CH 8057 Zurich, Switzerland
    J Biol 2:20. 2003
    ..In this study, we present a genetic characterization of dFOXO, the only Drosophila FOXO ortholog...
  41. 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
    ..Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors...
  42. ncbi Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway
    Ryan S Udan
    Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Cell Biol 5:914-20. 2003
    ..We find that Sav binds to a regulatory domain of Hpo that is essential for its function, indicating that Hpo acts together with Sav and Wts in a signalling module that coordinately regulates cell proliferation and apoptosis...
  43. ncbi Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size
    C J Potter
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, CT 06536, USA
    Cell 105:357-68. 2001
    ..We have isolated a mutation in the Drosophila homolog of TSC1 (Tsc1). Cells mutant for Tsc1 are dramatically increased in size yet differentiate normally...
  44. ncbi A nutrient sensor mechanism controls Drosophila growth
    Julien Colombani
    Institute for Signaling, Developmental Biology and Cancer Research, UMR6543 CNRS Parc Valrose, 06108, Cedex 2, Nice, France
    Cell 114:739-49. 2003
    ..This involves TSC/TOR signaling in the fat body, and a remote inhibition of organismal growth via local repression of PI3-kinase ..
  45. pmc A systematic screen for tube morphogenesis and branching genes in the Drosophila tracheal system
    Amin S Ghabrial
    Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA
    PLoS Genet 7:e1002087. 2011
    ....
  46. ncbi Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex
    Vanishree Murthy
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 279:1351-8. 2004
    ..Sclerosis Complex (TSC) is an autosomal dominant disorder associated with mutations in TSC1, which codes for hamartin, or TSC2, which codes for tuberin...
  47. 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
    There has been much interest in determining the molecular and cellular functions of hamartin and tuberin, which are encoded by the genes TSC1 and TSC2 that are mutated in the tuberous sclerosis complex disease...
  48. pmc Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells
    Alla Amcheslavsky
    University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Cell Biol 193:695-710. 2011
    ..We demonstrate in this paper that the tuberous sclerosis complex (TSC) plays a critical role in balancing ISC growth and division...
  49. 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
    ..This disease is caused by mutations in the TSC1 or TSC2 tumor suppressor genes; the molecular mechanisms underlying the activity of these have long been elusive...
  50. ncbi Akt regulates growth by directly phosphorylating Tsc2
    Christopher J Potter
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536 0812, USA
    Nat Cell Biol 4:658-65. 2002
    ..growth by phosphorylating the tuberous sclerosis complex 2 (Tsc2) tumour suppressor and inhibiting formation of a Tsc1-Tsc2 complex...
  51. 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...
  52. doi Basic mechanisms of longevity: A case study of Drosophila pro-longevity genes
    Ekaterina N Proshkina
    Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia Institute of Biology of Komi Science Center of Ural Branch of RAS, 167982 Syktyvkar, Russia
    Ageing Res Rev 24:218-31. 2015
    ..The majority of longevity-associated genes regulates metabolism and stress resistance, and belongs to the IGF-1R, PI3K, PKB, AMPK and TOR metabolic regulation cluster and the FOXO, HDAC, p53 stress response cluster...
  53. doi Forkhead, a new cross regulator of metabolism and innate immunity downstream of TOR in Drosophila
    Disha Varma
    Developmental Genetics and Molecular Physiology, LIMES Institute, University of Bonn, Carl Troll Str 31, 53115 Bonn, Germany
    J Insect Physiol 69:80-8. 2014
    ..We found that downregulation of TOR by feeding the drug rapamycin or by overexpressing the negative TOR regulators TSC1/TSC2, resulted in a specific induction of the AMPs Diptericin (Dpt) and Metchnikowin (Mtk)...
  54. pmc The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila
    Y Wei
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
    Cell Death Differ 21:1460-8. 2014
    ..Finally, we demonstrate that Nprl2/3 work in concert with the TORC1 inhibitors Tsc1/2 to fine tune TORC1 activity during oogenesis and that Tsc1 is a critical downstream effector of Akt1 in the ..
  55. doi Axon regrowth during development and regeneration following injury share molecular mechanisms
    Shiri P Yaniv
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Curr Biol 22:1774-82. 2012
    ..Despite emerging insights into MB γ-neuron axon pruning, nothing is known about the ensuing axon re-extension...
  56. pmc Differences in levels of the transmembrane protein Crumbs can influence cell survival at clonal boundaries
    Yassi Hafezi
    Department of Molecular and Cell Biology, University of California, Berkeley, 361 LSA, Berkeley, CA 94720 3200, USA
    Dev Biol 368:358-69. 2012
    ..Thus, Crb may be part of a "surveillance mechanism" that is responsible for the cell death that is observed at the boundaries of mutant clones in these cases...
  57. pmc High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila
    Ryan T Birse
    NASCR Center, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Cell Metab 12:533-44. 2010
    ..Moreover, reducing insulin-TOR activity (by expressing TSC1-2, 4EBP or FOXO), or increasing lipase expression-only within the myocardium-suffices to efficiently alleviate ..
  58. doi Conservation of structural and functional elements of TSC1 and TSC2: a bioinformatic comparison across animal models
    Jaco Serfontein
    Cambridgeshire and Peterborough NHS Foundation Trust, Addenbrooke s Hospital, Hills Road, Cambridge, UK
    Behav Genet 41:349-56. 2011
    The tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) proteins act as integrators of a range of intracellular signalling pathways...
  59. pmc Drosophila happyhour modulates JNK-dependent apoptosis
    D Lam
    Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester, UK
    Cell Death Dis 1:e66. 2010
    ..Together, our results show that hppy has a JNK-dependent proapoptotic function in Drosophila, which reinforces the hypothesis that MAP4K3 might act as tumour suppressor by regulating apoptosis in higher eukaryotes...
  60. pmc The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila
    Jacques Montagne
    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    PLoS Genet 6:e1000937. 2010
    ..These results provide the first molecular link between the dS6K pathway, critical in controlling nutrient-dependent growth, and that of DHR3, a major mediator of ecdysone signaling, which, acting together, coordinate metamorphosis...
  61. 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...
  62. doi The protein phosphatase PP2A-B' subunit Widerborst is a negative regulator of cytoplasmic activated Akt and lipid metabolism in Drosophila
    Natalia Vereshchagina
    Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford OX1 3QX, UK
    J Cell Sci 121:3383-92. 2008
    ....
  63. 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...
  64. 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...
  65. pmc AMPK supports growth in Drosophila by regulating muscle activity and nutrient uptake in the gut
    Michelle L Bland
    Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA
    Dev Biol 344:293-303. 2010
    ..Furthermore, our data show that in Drosophila, AMPK performs an essential cell-nonautonomous function, serving the needs of the organism by promoting activity of the visceral musculature and, consequently, nutrient intake...
  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
    ..Surprisingly, however, TORC2 does not regulate cell growth via its best-characterized target, AKT. Our findings support the possible application of TORC2-specific drugs in cancer therapy...
  67. doi Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding
    Eliana Marinari
    Medical Research Council Laboratory of Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
    Nature 484:542-5. 2012
    ..Because live-cell delamination constitutes a mechanistic link between epithelial hyperplasia and cell invasion, this is likely to have important implications for our understanding of the early stages of cancer development...
  68. doi Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila
    Billel Benmimoun
    Universite de Toulouse, UPS, CBD Centre de Biologie du Développement, Bâtiment 4R3, 118 route de Narbonne, F 31062 Toulouse, France
    Development 139:1713-7. 2012
    ..Hence, our study highlights the role of the IIS/TOR pathways in orchestrating hematopoietic progenitor fate and links blood cell fate to nutritional status...
  69. pmc Relationship between growth arrest and autophagy in midgut programmed cell death in Drosophila
    D Denton
    Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia
    Cell Death Differ 19:1299-307. 2012
    ..Despite the roles of autophagy in both survival and death, our findings suggest that autophagy induction occurs in response to similar signals in both scenarios...
  70. ncbi The growth regulators warts/lats and melted interact in a bistable loop to specify opposite fates in Drosophila R8 photoreceptors
    Tamara Mikeladze-Dvali
    Department of Biology, Center for Developmental Genetics, New York University, New York, New York 10003, USA
    Cell 122:775-87. 2005
    ..This represents an unexpected postmitotic role for genes controlling cell proliferation (warts and its partner hippo and salvador) and cell growth (melted)...
  71. ncbi Tor signalling in bugs, brain and brawn
    Estela Jacinto
    Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Nat Rev Mol Cell Biol 4:117-26. 2003
    ..Furthermore, TOR, by associating with regulatory proteins and inhibiting phosphatases, controls the activity of multiphosphorylated effectors...
  72. ncbi The tuberous sclerosis complex (TSC) pathway and mechanism of size control
    C J Potter
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
    Biochem Soc Trans 31:584-6. 2003
    ..PTEN (phosphatase and tensin homologue deleted on chromosome 10), and the tuberous sclerosis complex (TSC) genes, Tsc1 and Tsc2...
  73. ncbi hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts
    Shian Wu
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Cell 114:445-56. 2003
    ..A human homolog of hpo completely rescues the overgrowth phenotype of Drosophila hpo mutants, suggesting that hpo might play a conserved role for growth control in mammals...
  74. ncbi Growth signaling: TSC takes its place
    Steven J Marygold
    Growth Regulation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, WC2A 3PX, London, UK
    Curr Biol 12:R785-7. 2002
    The protein products of the tumor suppressor genes tuberous sclerosis complex 1 and 2 form a protein complex, TSC1-TSC2, that inhibits growth...
  75. ncbi Hippo and its mission for growth control
    Hyung Don Ryoo
    Nat Cell Biol 5:853-5. 2003
  76. ncbi Tuberous sclerosis complex genes: from flies to human genetics
    M Hengstschlager
    Obstetrics and Gynecology, University of Vienna, Prenatal Diagnosis and Therapy, Wahringer Gurtel, Austria
    Arch Dermatol Res 293:383-6. 2001
  77. ncbi Tuberous sclerosis gene products in proliferation control
    M Hengstschlager
    Obstetrics and Gynecology, Prenatal Diagnosis and Therapy, University of Vienna, Wahringer Gurtel 18 20, A 1090, Vienna, Austria
    Mutat Res 488:233-9. 2001
    ..characteristically occurring in TSC patients, suggested a tumor suppressor function for their gene products hamartin and tuberin...
  78. ncbi Mechanisms of size control
    C J Potter
    Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, Connecticut 06536 0812, USA
    Curr Opin Genet Dev 11:279-86. 2001
    ..The mechanisms of organ size control could also be critical targets for evolutionary events or disease processes such as tumorigenesis...
  79. ncbi Neuronal differentiation: TOR and insulin receptor pathways set the tempo
    Pierre Leopold
    Institute for Signaling, Developmental Biology and Cancer Centre National de la Recherche Scientifique Parc Valrose, 06108 Nice Cedex 2, France
    Cell 119:4-5. 2004
    ..A recent study reveals a novel role for these pathways in controlling the timing of neuronal differentiation during Drosophila development, thus allowing a tight coordination between growth and differentiation programs...
  80. pmc Mutations in the Drosophila orthologs of the F-actin capping protein alpha- and beta-subunits cause actin accumulation and subsequent retinal degeneration
    Ivana Delalle
    Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
    Genetics 171:1757-65. 2005
    ..In its absence, cells progressively accumulate actin filaments and eventually die. A possible role for their human orthologs in neurodegenerative disease merits further investigation...
  81. ncbi The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis
    Fisun Hamaratoglu
    Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Nat Cell Biol 8:27-36. 2006
    ..Our genetic and biochemical data place Merlin and Expanded upstream of Hippo and identify a pathway through which they act as tumour-suppressor genes...
  82. ncbi The tumor-suppressor gene fat controls tissue growth upstream of expanded in the hippo signaling pathway
    Elizabeth Silva
    Samuel Lunenfeld Research Institute and Department of Medical Genetics and Microbiology, University of Toronto, Toronto M5G 1X5, Canada
    Curr Biol 16:2081-9. 2006
    ..The cytoskeletal proteins Merlin and Expanded colocalize at apical junctions and function redundantly upstream of Hippo. It is not clear how they regulate growth or how they are localized to apical junctions...
  83. 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...
  84. 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
    ..These data imply that pathological situations that increase TOR activity might perturb the ability of the whole organism to cope with stress causing disease progression and aging...
  85. ncbi Specialized hepatocyte-like cells regulate Drosophila lipid metabolism
    Eugenio Gutierrez
    Medical Research Council, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Nature 445:275-80. 2007
    ..These findings provide evidence that some lipid-processing functions of the mammalian liver are performed in insects by oenocytes...
  86. 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...
  87. 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
    ..sclerosis complex is a dominant genetic disorder produced by mutations in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by hamartomatous tumors, and is associated with severe neurological and behavioral ..
  88. 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...
  89. 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...
  90. pmc The Drosophila deoxyhypusine hydroxylase homologue nero and its target eIF5A are required for cell growth and the regulation of autophagy
    Prajal H Patel
    Program in Developmental Biology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    J Cell Biol 185:1181-94. 2009
    ..Our data also indicate that nero and eIF5A are required for cell growth and affect autophagy and protein synthesis...
  91. 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...
  92. pmc Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster
    Mathieu Miron
    Department of Biochemistry and McGill Cancer Center, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Mol Cell Biol 23:9117-26. 2003
    ..Surprisingly, RNAi of dAkt also affected insulin-stimulated phosphorylation of dS6K, indicating that dAkt may also play a role in dS6K phosphorylation...
  93. ncbi The bantam microRNA is a target of the hippo tumor-suppressor pathway
    Riitta Nolo
    Department of Biochemistry and Molecular Biology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Curr Biol 16:1895-904. 2006
    ..However, how Yorkie regulates growth, and thus the identities of downstream target genes that mediate the effects of Hippo signaling, are largely unknown...
  94. ncbi The coupling of cell growth to the cell cycle
    N Tapon
    Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA
    Curr Opin Cell Biol 13:731-7. 2001
    ..This work has revealed interesting and unexpected relationships between mechanisms that regulate growth and the cell cycle machinery...

Research Grants2

  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. 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. ..