Tsc2

Summary

Gene Symbol: Tsc2
Description: tuberous sclerosis 2
Alias: Nafld, Tcs2, tuberin, tuberous sclerosis 2 protein homolog
Species: mouse

Top Publications

  1. ncbi Generation of a transcriptional map for a 700-kb region surrounding the polycystic kidney disease type 1 (PKD1) and tuberous sclerosis type 2 (TSC2) disease genes on human chromosome 16p3.3
    T C Burn
    Department of Human Genetics, Integrated Genetics, Framingham, Massachusetts 01701, USA
    Genome Res 6:525-37. 1996
  2. pmc The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway
    Tiffiney R Hartman
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19090, USA
    Hum Mol Genet 18:151-63. 2009
  3. ncbi Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice
    T Kobayashi
    Department of Experimental Pathology, Cancer Institute, Tokyo, Japan
    Cancer Res 59:1206-11. 1999
  4. pmc Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background
    H Onda
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 104:687-95. 1999
  5. ncbi Molecular genetic advances in tuberous sclerosis
    J P Cheadle
    Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK
    Hum Genet 107:97-114. 2000
  6. pmc A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice
    T Kobayashi
    Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170 8455, Japan
    Proc Natl Acad Sci U S A 98:8762-7. 2001
  7. ncbi TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex
    M Nellist
    Department of Clinical Genetics, Erasmus University, 3015 GE Rotterdam, The Netherlands
    Hum Mol Genet 10:2889-98. 2001
  8. ncbi A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells
    David J Kwiatkowski
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, LM 302, Boston, MA 02115, USA
    Hum Mol Genet 11:525-34. 2002
  9. ncbi Heterozygosity for the tuberous sclerosis complex (TSC) gene products results in increased astrocyte numbers and decreased p27-Kip1 expression in TSC2+/- cells
    Erik J Uhlmann
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Oncogene 21:4050-9. 2002
  10. ncbi Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 10:151-62. 2002

Research Grants

  1. PML, PLZF, NPM AND NUMA IN THE PATHOGENESIS OF APL
    Pier Paolo Pandolfi; Fiscal Year: 2005
  2. 2005 Cancer Models and Mechanisms Gordon Conference
    Pier Paolo Pandolfi; Fiscal Year: 2005
  3. Control of Protein Translation in Cancer Pathogenesis
    Pier Paolo Pandolfi; Fiscal Year: 2008
  4. FUSION PROTEINS IN THE MOLECULAR PATHOGENESIS OF APL
    Pier Paolo Pandolfi; Fiscal Year: 2009
  5. MURINE MODELS OF TSC 1: MECHANISMS AND THERAPIES
    David Kwiatkowski; Fiscal Year: 2001
  6. GELSOLIN: ROLES IN APOPTOSIS AND TUMOR DEVELOPMENT
    David Kwiatkowski; Fiscal Year: 2003
  7. GENOTYPING CENTER FOR INNATE IMMUNITY PGA
    David Kwiatkowski; Fiscal Year: 2004
  8. Preclinical Studies of Rapamycin for TSC Brain Disease
    David Kwiatkowski; Fiscal Year: 2006
  9. Tuberous Sclerosis: Mutations and Murine Models
    David Kwiatkowski; Fiscal Year: 2006
  10. The Role of Tuberin in Smooth Muscle Cell Proliferation
    Geraldine Finlay; Fiscal Year: 2007

Scientific Experts

  • Dan Ehninger
  • Elena N Atochina-Vasserman
  • Yoko Obayashi
  • Rosa Bernardi
  • Troy A Hornberger
  • Pier Paolo Pandolfi
  • Soo Han Bae
  • Lyn M Moir
  • Samy L Habib
  • Kristen Pollizzi
  • Brendan Manning
  • T C Burn
  • David Kwiatkowski
  • Geraldine Finlay
  • ping la
  • Alice B Brown
  • Mark Nellist
  • Michael J Gambello
  • Okio Hino
  • Hongbing Zhang
  • Jingxiang Huang
  • Toshiyuki Kobayashi
  • Elena A Goncharova
  • Margit Rosner
  • Li Ma
  • Tetsuo Noda
  • Raymond S Yeung
  • Tomoko Kaneko-Tarui
  • James Brugarolas
  • Kun Liang Guan
  • Ken Inoki
  • Hiroaki Onda
  • Nicholas C Wolff
  • Xiaojun Zha
  • Christian C Dibble
  • Yao Lin
  • Maki Koyanagi
  • Craig Stevens
  • Tsukasa Suzuki
  • Yutaka Shigeyama
  • Xiuyun Jiang
  • Mustafa Sahin
  • Elizabeth A Barnes
  • Markus Hengstschlager
  • David H Gutmann
  • Irina I Nagy
  • Y Zhou
  • Victoria Tsai
  • Rachel Miloslavski
  • Guomei Tang
  • Jian Yang
  • Hannah Crossland
  • Karl Katholnig
  • Brittany L Jacobs
  • Emily R Gilbert
  • JOSE M TEIXEIRA
  • Durga N Tripathi
  • Marina Bayeva
  • Victoria Makovski
  • Pradeep S Tanwar
  • Wenjuan Ru
  • Itzamarie Chévere-Torres
  • Carmine Settembre
  • Chen Yu Wang
  • Oded Meyuhas
  • Vera P Krymskaya
  • Judith Kasir
  • Nadine Cybulski
  • Irene Khavin
  • Dmitry A Goncharov
  • Markus A Ruegg
  • Samuel Peña-Llopis
  • Xian Jin Xie
  • Danqing Zhang
  • Silvia Vega-Rubin-de-Celis
  • Peiyong Zhai
  • Sutapa Banerjee
  • Sei Yoshida
  • Cheryl Lyn Walker
  • Ling Hui Zeng
  • Benjamin D Auerbach
  • Andrey Parkhitko
  • Fang Wang
  • Huangxuan Shen
  • Yinfei Tan
  • Jiumei Cao
  • T Kobayashi
  • Jianhui Ma
  • David M Young
  • Mitsunori Miyazaki

Detail Information

Publications126 found, 100 shown here

  1. ncbi Generation of a transcriptional map for a 700-kb region surrounding the polycystic kidney disease type 1 (PKD1) and tuberous sclerosis type 2 (TSC2) disease genes on human chromosome 16p3.3
    T C Burn
    Department of Human Genetics, Integrated Genetics, Framingham, Massachusetts 01701, USA
    Genome Res 6:525-37. 1996
    ..3 has been shown to contain the polycystic kidney disease 1 (PKD1) and the tuberous sclerosis type 2 (TSC2) disease genes. An estimated 20 genes are present in this region of chromosome 16...
  2. pmc The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway
    Tiffiney R Hartman
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19090, USA
    Hum Mol Genet 18:151-63. 2009
    ..We report here that hamartin (TSC1) localizes to the basal body of the primary cilium, and that Tsc1(-/-) and Tsc2(-/-) mouse embryonic fibroblasts (MEFs) are significantly more likely to contain a primary cilium than wild-type ..
  3. ncbi Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice
    T Kobayashi
    Department of Experimental Pathology, Cancer Institute, Tokyo, Japan
    Cancer Res 59:1206-11. 1999
    ..difference between man and rat is currently unknown, and the physiological function of the TSC2/Tsc2 product (tuberin) is not fully understood. To investigate these unsolved problems, we have generated a Tsc2 mutant mouse...
  4. pmc Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background
    H Onda
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 104:687-95. 1999
    ..genetic disorder in which benign hamartomas develop in multiple organs, caused by mutations in either TSC1 or TSC2. We developed a murine model of Tsc2 disease using a gene targeting approach...
  5. ncbi Molecular genetic advances in tuberous sclerosis
    J P Cheadle
    Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK
    Hum Genet 107:97-114. 2000
    ..for the disorder, through to gaining insights into the functions of their protein products hamartin and tuberin, and the identification and engineering of animal models...
  6. pmc A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice
    T Kobayashi
    Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170 8455, Japan
    Proc Natl Acad Sci U S A 98:8762-7. 2001
    ..by the development of hamartomas in various organs and is caused by a germ-line mutation in either TSC1 or TSC2 tumor suppressor genes...
  7. ncbi TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex
    M Nellist
    Department of Clinical Genetics, Erasmus University, 3015 GE Rotterdam, The Netherlands
    Hum Mol Genet 10:2889-98. 2001
    ..TSC1 and TSC2 encode two large novel proteins called hamartin and tuberin, respectively...
  8. ncbi A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells
    David J Kwiatkowski
    Genetics Laboratory, Hematology Division, Brigham and Women s Hospital, Harvard Medical School, 221 Longwood Avenue, LM 302, Boston, MA 02115, USA
    Hum Mol Genet 11:525-34. 2002
    Tuberous sclerosis (TSC) is a autosomal dominant genetic disorder caused by mutations in either TSC1 or TSC2, and characterized by benign hamartoma growth. We developed a murine model of Tsc1 disease by gene targeting...
  9. ncbi Heterozygosity for the tuberous sclerosis complex (TSC) gene products results in increased astrocyte numbers and decreased p27-Kip1 expression in TSC2+/- cells
    Erik J Uhlmann
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Oncogene 21:4050-9. 2002
    ..mouse embryonic fibroblasts, p27-Kip1 expression was decreased compared to wild type cells, and was reversed by tuberin re-expression in Tsc2-/- MEFs...
  10. ncbi Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 10:151-62. 2002
    ..This approach identifies the tuberous sclerosis complex-2 gene product, tuberin, as a potential target of Akt/PKB...
  11. pmc Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent
    Anja Jaeschke
    Cancer Research UK Centre for Cell and Molecular Biology, Institute for Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    J Cell Biol 159:217-24. 2002
    ..genetic disorder, characterized by mutations in either TSC1 or TSC2, whose gene products hamartin (TSC1) and tuberin (TSC2) constitute a putative tumor suppressor complex (TSC1-2; van Slegtenhorst, M., M. Nellist, B...
  12. ncbi Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway
    Hiroaki Onda
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Neurosci 21:561-74. 2002
    ..b>Tsc2 null murine neuroepithelial progenitor (NEP) cells display persistent growth when growth factors are withdrawn, ..
  13. ncbi TSC2 regulates VEGF through mTOR-dependent and -independent pathways
    James B Brugarolas
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Cancer Cell 4:147-58. 2003
    Inactivation of the TSC2 tumor suppressor protein causes tuberous sclerosis complex (TSC), a disease characterized by highly vascular tumors. TSC2 has multiple functions including inhibition of mTOR (mammalian target of Rapamycin)...
  14. pmc Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR
    Hongbing Zhang
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 112:1223-33. 2003
    Tuberous sclerosis (TSC) is a familial tumor syndrome due to mutations in TSC1 or TSC2, in which progression to malignancy is rare...
  15. ncbi TSC2 mediates cellular energy response to control cell growth and survival
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 115:577-90. 2003
    Mutations in either the TSC1 or TSC2 tumor suppressor gene are responsible for Tuberous Sclerosis Complex...
  16. pmc The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins
    Laura S Harrington
    Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Rd, London SW3 6JB, England, UK
    J Cell Biol 166:213-23. 2004
    ..Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors...
  17. pmc Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
    James Brugarolas
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 18:2893-904. 2004
    ..a process involving the activation of AMP-activated protein kinase (AMPK) by LKB1 and subsequent phosphorylation of TSC2, the mechanism of mTOR inhibition by hypoxia is not known...
  18. ncbi Efficacy of a rapamycin analog (CCI-779) and IFN-gamma in tuberous sclerosis mouse models
    Laifong Lee
    Division of Hematology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Genes Chromosomes Cancer 42:213-27. 2005
    ..Disease-causing mutations in the TSC1 or TSC2 gene lead to increased mammalian target of rapamycin (mTOR) kinase activity in the conserved mTOR signaling pathway,..
  19. ncbi Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis
    Li Ma
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 121:179-93. 2005
    Tuberous sclerosis (TSC) is a tumor syndrome caused by mutation in TSC1 or TSC2 genes. TSC tumorigenesis is not always accompanied by loss of heterozygosity (LOH)...
  20. pmc Aberrant beta-catenin signaling in tuberous sclerosis
    Baldwin C Mak
    Department of Surgery, University of Washington, 1959 NE Pacific St, Box 356410, Seattle, WA 98195, USA
    Am J Pathol 167:107-16. 2005
    ..and components of the beta-catenin degradation complex was dependent on Wnt stimulation such that binding of tuberin to GSK3 and Axin was reduced in the presence of Wnt whereas the tuberin-Dishevelled interaction was increased...
  21. pmc Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression
    Li Ma
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Genes Dev 19:1779-86. 2005
    The role of tumor suppressor haploinsufficiency in oncogenesis is still poorly understood. The PTEN and TSC2 tumor suppressors function to antagonize mTOR (mammalian target of rapamycin) activation by Akt; hence, compound heterozygous ..
  22. pmc Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2
    Brendan D Manning
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Genes Dev 19:1773-8. 2005
    The PTEN and TSC2 tumor suppressors inhibit mammalian target of rapamycin (mTOR) signaling and are defective in distinct hamartoma syndromes...
  23. ncbi Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2
    Sohail F Tavazoie
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Neurosci 8:1727-34. 2005
    Mutations in the TSC1 or TSC2 tumor suppressor genes lead to tuberous sclerosis complex (TSC), a dominant hamartomatous disorder that often presents with mental retardation, epilepsy and autism...
  24. pmc Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling
    Maurice Phillip DeYoung
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA
    Genes Dev 22:239-51. 2008
    ..Here, we demonstrate that hypoxia and REDD1 suppress mammalian TORC1 (mTORC1) activity by releasing TSC2 from its growth factor-induced association with inhibitory 14-3-3 proteins...
  25. pmc Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice
    Yutaka Shigeyama
    Department of Internal Medicine, Division of Diabetes, Metabolism, and Endocrinology, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    Mol Cell Biol 28:2971-9. 2008
    ..Given the role of tuberous sclerosis complex 2 (TSC2) as an upstream molecule of mTOR (mammalian target of rapamycin), we examined the effect of TSC2 deficiency on beta-..
  26. pmc Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
    Mol Cell 29:541-51. 2008
    ..Loss of the tuberous sclerosis complex genes (TSC1 or TSC2) leads to constitutive activation of mTOR and downstream signaling elements, resulting in the development of tumors,..
  27. pmc Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis
    Dan Ehninger
    Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, 695 Charles E Young Drive South, Los Angeles, California 90095, USA
    Nat Med 14:843-8. 2008
    Tuberous sclerosis is a single-gene disorder caused by heterozygous mutations in the TSC1 (9q34) or TSC2 (16p13.3) gene and is frequently associated with mental retardation, autism and epilepsy...
  28. pmc Tuberous sclerosis complex proteins control axon formation
    Yong Jin Choi
    The F M Kirby Neurobiology Center, Department of Neurology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 22:2485-95. 2008
    Axon formation is fundamental for brain development and function. TSC1 and TSC2 are two genes, mutations in which cause tuberous sclerosis complex (TSC), a disease characterized by tumor predisposition and neurological abnormalities ..
  29. pmc IKKbeta suppression of TSC1 function links the mTOR pathway with insulin resistance
    Dung Fang Lee
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Int J Mol Med 22:633-8. 2008
    ..V-Lepob/J mice. Collectively, dysregulation of the TSC1/ TSC2/mTOR signaling pathway by IKKbeta is a common molecular switch for both cancer pathogenesis and diet- and obesity-..
  30. pmc The TSC-mTOR pathway mediates translational activation of TOP mRNAs by insulin largely in a raptor- or rictor-independent manner
    Ilona Patursky-Polischuk
    Department of Biochemistry, Hebrew University Hadassah Medical School, Jerusalem, Israel
    Mol Cell Biol 29:640-9. 2009
    ..This translational activation involves the tuberous sclerosis complex (TSC), as the knockout of TSC1 or TSC2 rescues TOP mRNAs from translational repression in mitotically arrested cells...
  31. pmc Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse
    Sharon W Way
    Division of Medical Genetics, Department of Pediatrics, University of Texas Health Science Center, Houston, TX 77030, USA
    Hum Mol Genet 18:1252-65. 2009
    ..developmental perturbations that lead to these brain lesions, we created a mouse model that selectively deletes the Tsc2 gene from radial glial progenitor cells in the developing cerebral cortex and hippocampus...
  32. doi Defects in cell polarity underlie TSC and ADPKD-associated cystogenesis
    Cleo S Bonnet
    Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
    Hum Mol Genet 18:2166-76. 2009
    ..Here, we show that many of the earliest renal lesions from Tsc1+/- and Tsc2+/- mice do not exhibit mTOR activation, suggesting that pharmacological targeting of an alternative pathway may be ..
  33. pmc Equivalent benefit of mTORC1 blockade and combined PI3K-mTOR blockade in a mouse model of tuberous sclerosis
    Kristen Pollizzi
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Mol Cancer 8:38. 2009
    ..Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1 and suppression of AKT...
  34. pmc Signaling events downstream of mammalian target of rapamycin complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors
    Jingxiang Huang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Massachusetts General Hospital, Boston, Massachusetts 02115, USA
    Cancer Res 69:6107-14. 2009
    Mutations in the TSC1 and TSC2 tumor suppressor genes give rise to the neoplastic disorders tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis...
  35. pmc Tsc2-Rheb signaling regulates EphA-mediated axon guidance
    Duyu Nie
    The F M Kirby Neurobiology Center, Department of Neurology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
    Nat Neurosci 13:163-72. 2010
    Tuberous sclerosis complex is a disease caused by mutations in the TSC1 or TSC2 genes, which encode a protein complex that inhibits mTOR kinase signaling by inactivating the Rheb GTPase...
  36. pmc Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism
    David M Young
    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 107:11074-9. 2010
    ..To explore social communication and interaction in TSC2 heterozygous mice, we recorded ultrasonic vocalizations (USV) and found that although both wild-type (WT) and ..
  37. pmc Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex
    Ling Hui Zeng
    Department of Pharmacy, Zhejiang University City College, Hangzhou, Zhejiang 310015, China
    Hum Mol Genet 20:445-54. 2011
    ..Two genes, TSC1 and TSC2, encoding the proteins hamartin and tuberin, respectively, have been identified as causing TSC...
  38. pmc Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice
    D Ehninger
    DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany
    Mol Psychiatry 17:62-70. 2012
    ..Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of TSC-related ASD...
  39. pmc Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia
    Nicholas C Wolff
    University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9133, USA
    Mol Cell Biol 31:1870-84. 2011
    ..We previously reported that mTORC1 regulation by hypoxia involves Redd1 and the Tsc1/Tsc2 complex...
  40. pmc mTORC2 is required for proliferation and survival of TSC2-null cells
    Elena A Goncharova
    Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Cell Biol 31:2484-98. 2011
    Mutational inactivation of the tumor suppressor tuberous sclerosis complex 2 (TSC2) constitutively activates mTORC1, increases cell proliferation, and induces the pathological manifestations observed in tuberous sclerosis (TS) and in ..
  41. pmc Regulation of TFEB and V-ATPases by mTORC1
    Samuel Peña-Llopis
    Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
    EMBO J 30:3242-58. 2011
    ..These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis...
  42. pmc Mutations causing syndromic autism define an axis of synaptic pathophysiology
    Benjamin D Auerbach
    Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 480:63-8. 2011
    ..Using electrophysiological and biochemical assays of neuronal protein synthesis in the hippocampus of Tsc2(+/-) and Fmr1(-/y) mice, here we show that synaptic dysfunction caused by these mutations actually falls at ..
  43. pmc Metabotropic glutamate receptor-dependent long-term depression is impaired due to elevated ERK signaling in the ΔRG mouse model of tuberous sclerosis complex
    Itzamarie Chévere-Torres
    Center for Neural Science, New York University, New York, NY 10003, USA
    Neurobiol Dis 45:1101-10. 2012
    ..We measured the impact of TSC2-GAP mutations on the mTORC1 and ERK signaling pathways and protein synthesis-dependent hippocampal synaptic ..
  44. pmc TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1
    Christian C Dibble
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Mol Cell 47:535-46. 2012
    The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex, which limits cell growth in response to poor growth conditions...
  45. pmc Fetal brain mTOR signaling activation in tuberous sclerosis complex
    Victoria Tsai
    PENN Epilepsy Center, Department of Neurology and University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA
    Cereb Cortex 24:315-27. 2014
    ..To date, there are no reports of mTORC1 and mTORC2 activation in fetal tubers or in neural progenitor cells lacking Tsc2. We demonstrate mTORC1 activation by immunohistochemical detection of substrates phospho-p70S6K1 (T389) and phospho-..
  46. pmc Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner
    Rachel Miloslavski
    Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel Canada, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    J Mol Cell Biol 6:255-66. 2014
    ..This mode of regulation involves TSC and Rheb, as knockout of TSC1 or TSC2 or overexpression of Rheb rescued TOP mRNA translation in oxygen-deprived cells...
  47. ncbi The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses
    Ewan M Smith
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 280:18717-27. 2005
    ..Recent work demonstrated the importance of the tuberous sclerosis protein TSC2 for regulation of mTOR by insulin...
  48. ncbi Generation of a conditional disruption of the Tsc2 gene
    Omar Hernandez
    Department of Pediatrics, Division of Medical Genetics, University of Texas Health Science Center, Houston 77030, USA
    Genesis 45:101-6. 2007
    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 gene. Patients afflicted with TSC develop tumors in various organ systems, but cerebral pathology is particularly severe...
  49. pmc Tuberous sclerosis complex proteins 1 and 2 control serum-dependent translation in a TOP-dependent and -independent manner
    Benoit Bilanges
    Cancer Research Institute, University of California, San Francisco, California, USA
    Mol Cell Biol 27:5746-64. 2007
    The tuberous sclerosis complex (TSC) proteins TSC1 and TSC2 regulate protein translation by inhibiting the serine/threonine kinase mTORC1 (for mammalian target of rapamycin complex 1)...
  50. doi A role of the mammalian target of rapamycin (mTOR) in glutamate-induced down-regulation of tuberous sclerosis complex proteins 2 (TSC2)
    Wenjuan Ru
    Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
    J Mol Neurosci 47:340-5. 2012
    ..In this study, we show that glutamate stimulation down-regulates TSC2 protein in cortical cultures via NMDA receptor (NMDAR) activation...
  51. pmc Altered LKB1/AMPK/TSC1/TSC2/mTOR signaling causes disruption of Sertoli cell polarity and spermatogenesis
    Pradeep S Tanwar
    Vincent Center for Reproductive Biology Thier 931, Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Hum Mol Genet 21:4394-405. 2012
    ..Loss of Tsc1 or Tsc2 copies the progressive Lkb1(cko) phenotype, suggesting that dysregulated activation of mTOR contributes to the ..
  52. doi Positioning ganglioside D3 as an immunotherapeutic target in lymphangioleiomyomatosis
    Emily R Gilbert
    Department of Medicine, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, USA
    Am J Pathol 183:226-34. 2013
    Tumors that develop in lymphangioleiomyomatosis (LAM) as a consequence of biallelic loss of TSC1 or TSC2 gene function express melanoma differentiation antigens...
  53. pmc Eccentric contractions increase the phosphorylation of tuberous sclerosis complex-2 (TSC2) and alter the targeting of TSC2 and the mechanistic target of rapamycin to the lysosome
    Brittany L Jacobs
    T A Hornberger Department of Comparative Biosciences, 2015 Linden Drive, Madison, WI 53706, USA
    J Physiol 591:4611-20. 2013
    ..of rapamycin (mTOR) signalling is associated with changes in phosphorylation of tuberous sclerosis complex-2 (TSC2) and targeting of mTOR and TSC2 to the lysosome...
  54. pmc Reactive nitrogen species regulate autophagy through ATM-AMPK-TSC2-mediated suppression of mTORC1
    Durga N Tripathi
    Institute for Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 110:E2950-7. 2013
    ..These data identify a nitrosative-stress signaling pathway that engages ATM and the LKB1 and TSC2 tumor suppressors to repress mTORC1 and regulate autophagy...
  55. pmc Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits
    Guomei Tang
    Department of Neurology, Columbia University Medical Center, New York, NY10032, USA
    Neuron 83:1131-43. 2014
    ..These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2 ± ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of ..
  56. pmc Hyperplasia and fibrosis in mice with conditional loss of the TSC2 tumor suppressor in Müllerian duct mesenchyme-derived myometria
    Tomoko Kaneko-Tarui
    Vincent Center for Reproductive Biology, Department of Obstetrics, Gynecology, and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Mol Hum Reprod 20:1126-34. 2014
    ..Loss of the Tuberous Sclerosis 2 (TSC2) tumor suppressor has been proposed as a mechanism important for the etiology of uterine leiomyomata based on the ..
  57. pmc TSC2/mTORC1 signaling controls Paneth and goblet cell differentiation in the intestinal epithelium
    Y Zhou
    Markey Cancer Center, The University of Kentucky, Lexington, KY, USA
    Cell Death Dis 6:e1631. 2015
    ..Previously, we have shown that tuberous sclerosis 2 (TSC2) positively regulates the expression of the goblet cell differentiation marker, MUC2, in intestinal cells...
  58. pmc Pharmacological targeting of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth in the mouse model of lymphangioleiomyomatosis
    Elena N Atochina-Vasserman
    Airway Biology Initiative, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania Pulmonary, Allergy and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania and
    Am J Physiol Lung Cell Mol Physiol 309:L1447-54. 2015
    ..LAM), a rare progressive lung disease associated with mutations of the tuberous sclerosis complex 2 (Tsc2) tumor suppressor gene, manifests by neoplastic growth of LAM cells, induction of cystic lung destruction, and ..
  59. pmc Impairment of Wnt11 function leads to kidney tubular abnormalities and secondary glomerular cystogenesis
    Irina I Nagy
    Biocenter Oulu, Laboratory of Developmental Biology, Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell Matrix Research, University of Oulu, Aapistie 5A, Oulu, 90014, Finland
    BMC Dev Biol 16:30. 2016
    ..The presence of Wnt11 in the emerging tubular system suggests that it may have certain roles later in the development of the epithelial ductal system...
  60. ncbi Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1
    Changhua Wang
    Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229, USA
    J Biol Chem 282:7991-6. 2007
    ..Finally, overexpression of wild-type Rheb (Ras homology-enriched in brain) or the TSC2 mutant lacking the AMPK phosphorylation site (TSC2S1345A) inhibited the insulin-sensitizing effect of adiponectin ..
  61. ncbi The TSC1 gene product hamartin interacts with NADE
    Sakiko Yasui
    Department of Neurobiology, School of Life Sciences, Tottori University Faculty of Medicine, Yonago 683 8503, Japan
    Mol Cell Neurosci 35:100-8. 2007
    ..These results indicate that hamartin binds to NADE to regulate neuronal cell function and loss of this association is likely to contribute to the brain pathology in TSC...
  62. pmc Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1
    Gianfranco Distefano
    Dulbecco Telethon Institute at Dibit San Raffaele, Via Olgettina 58, Milan, Italy
    Mol Cell Biol 29:2359-71. 2009
    ..Tsc2-dependent manner, by inhibiting the extracellular signal-regulated kinase (ERK)-mediated phosphorylation of tuberin in Ser664...
  63. doi Farnesylthiosalicylic acid (salirasib) inhibits Rheb in TSC2-null ELT3 cells: a potential treatment for lymphangioleiomyomatosis
    Victoria Makovski
    Department of Neurobiology, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    Int J Cancer 130:1420-9. 2012
    ..tuberous sclerosis complex (TSC), which includes products of the TSC1 and TSC2 genes encoding hamartin (TSC1) and tuberin (TSC2), respectively, and acts as a Rheb-specific GTPase-activating protein...
  64. pmc Ablation of TSC2 enhances insulin secretion by increasing the number of mitochondria through activation of mTORC1
    Maki Koyanagi
    Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan
    PLoS ONE 6:e23238. 2011
    We previously found that chronic tuberous sclerosis protein 2 (TSC2) deletion induces activation of mammalian target of rapamycin Complex 1 (mTORC1) and leads to hypertrophy of pancreatic beta cells from pancreatic beta cell-specific TSC2 ..
  65. doi TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade
    Xiaojun Zha
    State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
    Cancer Lett 313:211-7. 2011
    Aberrant activation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss or inactivation of TSC1/TSC2 protein complex, leads to negative feedback inhibition of Akt...
  66. pmc A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB
    Carmine Settembre
    Telethon Institute of Genetics and Medicine, Naples, Italy
    EMBO J 31:1095-108. 2012
    ..These data indicate that the lysosome senses its content and regulates its own biogenesis by a lysosome-to-nucleus signalling mechanism that involves TFEB and mTOR...
  67. pmc Tsc2, a positional candidate gene underlying a quantitative trait locus for hepatic steatosis
    Chen Yu Wang
    Department of Biochemistry, University of Wisconsin Madison, Madison, WI, USA
    J Lipid Res 53:1493-501. 2012
    Nonalchoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction and is associated with metabolic diseases, including obesity, insulin resistance, and type 2 diabetes...
  68. pmc TSC2 modulates cell adhesion and migration via integrin-α1β1
    Lyn M Moir
    Cell Biology, Woolcock Institute of Medical Research, PO Box M77, Missenden Rd, NSW, 2050, Australia
    Am J Physiol Lung Cell Mol Physiol 303:L703-10. 2012
    ..of the tumor suppressor genes tuberous sclerosis complex (TSC), in particular mutational inactivation of TSC2, enhances both cell proliferation and migration...
  69. pmc Prevention of alveolar destruction and airspace enlargement in a mouse model of pulmonary lymphangioleiomyomatosis (LAM)
    Elena A Goncharova
    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Sci Transl Med 4:154ra134. 2012
    ..disease is caused by mutational inactivation of the tumor suppressor gene tuberous sclerosis complex 1 (TSC1) or TSC2. By injecting TSC2-null cells into nude mice, we have developed a mouse model of LAM that is characterized by ..
  70. pmc mTOR regulates cellular iron homeostasis through tristetraprolin
    Marina Bayeva
    Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611, USA
    Cell Metab 16:645-57. 2012
    ..Taken together, our data uncover a link between metabolic, inflammatory, and iron-regulatory pathways, and point toward the existence of a yeast-like TTP-mediated iron conservation program in mammals...
  71. doi Renal tumours in a Tsc1+/- mouse model show epigenetic suppression of organic cation transporters Slc22a1, Slc22a2 and Slc22a3, and do not respond to metformin
    Jian Yang
    Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    Eur J Cancer 49:1479-90. 2013
    ..of 5' adenosine monophosphate-activated protein kinase (AMPK) in the presence or absence of a functional hamartin/tuberin (TSC1/TSC2) complex...
  72. doi Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage
    Soo Han Bae
    Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120 750, Korea
    Cell Metab 17:73-84. 2013
    ..Ablation of Sesn2 blocked Keap1 degradation and Nrf2 activation induced by refeeding and thereby increased the susceptibility of the liver to oxidative damage resulting from the acute stimulation of lipogenesis associated with refeeding...
  73. pmc p38α senses environmental stress to control innate immune responses via mechanistic target of rapamycin
    Karl Katholnig
    Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria
    J Immunol 190:1519-27. 2013
    ..Our data link p38α to mTOR signaling in myeloid immune cells that is decisive for tuning the immune response in dependence on the environmental milieu...
  74. pmc Mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation stabilizes ISCU protein: implications for iron metabolism
    Ping La
    Division of Neonatology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 288:12901-9. 2013
    ..Sustained ISCU protein levels enhanced by mTORC1 sensitized TSC2-null cells to iron deprivation due to constitutive ISC biogenesis-triggered iron demand, which outstrips supply...
  75. pmc Polycystin 1 is required for the structural integrity of blood vessels
    K Kim
    Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 97:1731-6. 2000
    ..These data reveal a requisite role for polycystin 1 in maintaining the structural integrity of the vasculature as well as epithelium and suggest that the nature of the PKD1 mutation contributes to the phenotypic variance in ADPKD...
  76. pmc Differential roles of GSK-3β during myocardial ischemia and ischemia/reperfusion
    Peiyong Zhai
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
    Circ Res 109:502-11. 2011
    ..Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated...
  77. pmc Focal adhesion kinase is required for IGF-I-mediated growth of skeletal muscle cells via a TSC2/mTOR/S6K1-associated pathway
    Hannah Crossland
    Medical Research Council Arthritis Research United Kingdom Centre of Excellence for Musculoskeletal Ageing Research, School of Graduate Entry Medicine and Health, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom
    Am J Physiol Endocrinol Metab 305:E183-93. 2013
    ..FAK Tyr³⁹⁷ phosphorylation and markedly suppressed phosphorylation of tuberous sclerosis complex 2 (TSC2) and critical downstream mTOR signaling (ribosomal S6 kinase, eIF4F assembly) in FAK shRNA cells (all P < 0...
  78. ncbi Cloning, developmental expression, and evidence for alternative splicing of the murine tuberous sclerosis (TSC2) gene product
    K K Kim
    Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis 46202 4800, USA
    Cell Mol Biol Res 41:515-26. 1995
    ..transcripts were observed in many adult tissues, protein analyses are required to determine whether functional tuberin protein is synthesized...
  79. ncbi Cardiomyocyte DNA synthesis and binucleation during murine development
    M H Soonpaa
    Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis 46202 4800, USA
    Am J Physiol 271:H2183-9. 1996
    ..Northern and Western blot analyses identified several candidate genes that were differentially expressed during the reduplicative and binucleation phases of cardiomyocyte growth...
  80. ncbi Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III
    A H Sarker
    Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama 700 8558, Japan
    J Mol Biol 282:761-74. 1998
    ..The mNthl1 gene was shown to lie immediately adjacent to the tuberous sclerosis 2 (Tsc2) gene in a 5'-to-5' orientation by sequence analysis and was assigned to chromosome 17A3 by in situ hybridization.
  81. ncbi Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues
    N G Pasteris
    Department of Human Genetics, University of Michigan Medical Center, Ann Arbor, Michigan, 48109 0688, USA
    Genomics 60:57-66. 1999
    ....
  82. ncbi Genetic variants of the tuberous sclerosis 2 tumour suppressor gene in mouse t haplotypes
    E V Kleymenova
    Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville 78957, USA
    Genet Res 74:139-44. 1999
    ..polymorphisms within the Tsc-2 coding region which did not result in amino acid changes in Tsc-2 gene product tuberin, this mutation substituted a phenylalanine for a conserved cysteine in tw5 tuberin...
  83. ncbi Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis
    L D Aicher
    Departments of Surgery, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 276:21017-21. 2001
    Hamartin and tuberin are products of the tumor suppressor genes, TSC1 and TSC2, respectively. When mutated, a characteristic spectrum of tumor-like growths develop resulting in the syndrome of tuberous sclerosis complex...
  84. ncbi Chromosomal localization of three vacuolar-H+ -ATPase 16 kDa subunit (ATP6V0C) genes in the murine genome
    A M Simckes
    Division of Pediatric Nephrology, The Children s Mercy Hospital, UMKC School of Medicine, Kansas City, MO 64108, USA
    Cytogenet Genome Res 97:111-5. 2002
    ..Atp6v0c maps to Chromosome 17, closely linked to the Tsc2 locus and D17Mit55...
  85. ncbi Protein kinase B alpha/Akt1 regulates placental development and fetal growth
    Zhong Zhou Yang
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058 Basel, Switzerland
    J Biol Chem 278:32124-31. 2003
    ..These data represent the first evidence for the role of PKB alpha and endothelial nitricoxide synthase in regulating placental development and provide an animal model for intrauterine growth retardation...
  86. ncbi Tuberin binds p27 and negatively regulates its interaction with the SCF component Skp2
    Margit Rosner
    Medical University of Vienna, Obstetrics and Gynecology, Prenatal Diagnosis and Therapy, Wahringer Gurtel 18 20, 1090 Vienna, Austria
    J Biol Chem 279:48707-15. 2004
    TSC1 (tuberous sclerosis complex 1) encoding hamartin and TSC2 encoding tuberin are tumor suppressor genes responsible for the autosomal dominantly inherited disease tuberous sclerosis...
  87. ncbi Cytoplasmic/nuclear localization of tuberin in different cell lines
    M Rosner
    Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
    Amino Acids 33:575-9. 2007
    ..The TSC gene products, hamartin and tuberin, form a complex, of which tuberin is assumed to be the functional component being involved in a wide variety of ..
  88. ncbi p27Kip1 localization depends on the tumor suppressor protein tuberin
    Margit Rosner
    Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Wahringer Gurtel 18 20, 1090 Vienna, Austria
    Hum Mol Genet 16:1541-56. 2007
    ..p27(Kip1) is regulated by its concentration as well as by its subcellular localization. Tuberin, encoded by the tuberous sclerosis tumor suppressor gene TSC2, is a potent negative cell cycle regulator...
  89. pmc Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53
    Chung Han Lee
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    EMBO J 26:4812-23. 2007
    ..Thus, loss of TSC1 or TSC2, the negative regulators of mTOR, results in dramatic accumulation of p53 and apoptosis in response to stress ..
  90. doi Tuberous sclerosis complex 2 loss-of-function mutation regulates reactive oxygen species production through Rac1 activation
    Tsukasa Suzuki
    Department of Applied Biology and Chemistry, Tokyo University of Agriculture, 1 1 1 Sakuragaoka, Setagaya Ku, Tokyo 156 8502, Japan
    Biochem Biophys Res Commun 368:132-7. 2008
    The products of the TSC1 (hamartin) and TCS2 (tuberin) tumor suppressor genes negatively regulate cell growth by inhibiting mTOR signaling...
  91. pmc Lipidomic analysis and electron transport chain activities in C57BL/6J mouse brain mitochondria
    Michael A Kiebish
    Biology Department, Boston College, Chestnut Hill, Massachusetts 02467, USA
    J Neurochem 106:299-312. 2008
    ..NS and Syn mitochondrial lipidomic heterogeneity could influence energy metabolism, which may contribute to metabolic compartmentation of the brain...
  92. pmc The TSC1-TSC2 complex is required for proper activation of mTOR complex 2
    Jingxiang Huang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Mol Cell Biol 28:4104-15. 2008
    ..mTOR complex 1 (mTORC1) phosphorylates S6K1, while mTORC2 phosphorylates Akt. The TSC1-TSC2 complex is a critical negative regulator of mTORC1...
  93. pmc Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner
    Latif Rachdi
    Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 105:9250-5. 2008
    ..The signaling pathways by which these growth signals modulate these processes have not been completely elucidated. Tsc2 is an attractive candidate to modulate these processes, because it is a converging point for growth factor and ..
  94. doi Peptide combinatorial libraries identify TSC2 as a death-associated protein kinase (DAPK) death domain-binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling
    Craig Stevens
    Institute of Genetics and Molecular Medicine, CRUK p53 Signal Transduction Laboratories, University of Edinburgh, Edinburgh EH4 2XR, United Kingdom
    J Biol Chem 284:334-44. 2009
    ..Peptide aptamer libraries were used to identify the tumor suppressor protein tuberin (TSC2) as a novel DAPK death domain-binding protein, and we evaluated whether DAPK is a positive or negative ..
  95. pmc PTEN deficiency is fully penetrant for prostate adenocarcinoma in C57BL/6 mice via mTOR-dependent growth
    Jorge Blando
    Department of Carcinogenesis, Research Division, Smithville, Texas 78957, USA
    Am J Pathol 174:1869-79. 2009
    ..Furthermore, double heterozygotes carrying both Pten and Tsc2-null alleles showed no increase relative to Pten(+/-) heterozygotes in either lesion development or progression...
  96. pmc Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway
    Hui H Zhang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA
    PLoS ONE 4:e6189. 2009
    ..One direct substrate that is inhibited by Akt-mediated phosphorylation is the tuberous sclerosis complex 2 (TSC2) protein, which associates with TSC1 and acts as a critical negative regulator of the mammalian target of rapamycin ..
  97. pmc TSC2 deficiency increases PTEN via HIF1alpha
    Lenin Mahimainathan
    Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229 3900, USA
    J Biol Chem 284:27790-8. 2009
    Substantial evidence suggests roles of TSC2 and PTEN in the development of cancer predisposition syndromes. Loss of TSC2 results in benign tumors, neurological disorders, and angiomyolipomas...
  98. doi Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles
    Deepak Adhikari
    Department of Medical Biochemistry and Biophysics, Umeå University SE 901 87, Umea, Sweden
    Mol Hum Reprod 15:765-70. 2009
    ..In this study, we provide some genetic evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the ..
  99. pmc Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade
    Jianhui Ma
    Department of Physiology and Pathophysiology, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People s Republic of China
    J Clin Invest 120:103-14. 2010
    ..lung lymphangioleiomyomatosis (LAM) and mouse kidney tumors with hyperactive mTOR due to tumor suppressor TSC1 or TSC2 deficiency exhibited enhanced STAT3/p63/Notch signaling...
  100. pmc Thoracic aortic disease in tuberous sclerosis complex: molecular pathogenesis and potential therapies in Tsc2+/- mice
    Jiumei Cao
    Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA
    Hum Mol Genet 19:1908-20. 2010
    ..TSC) is a genetic disorder with pleiotropic manifestations caused by heterozygous mutations in either TSC1 or TSC2. One of the less investigated complications of TSC is the formation of aneurysms of the descending aorta, which are ..
  101. pmc The apical complex couples cell fate and cell survival to cerebral cortical development
    Seonhee Kim
    Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Division of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Neuron 66:69-84. 2010
    ..These data highlight unexpected roles of the apical complex protein Pals1 in cell survival through interactions with mTOR signaling...

Research Grants11

  1. PML, PLZF, NPM AND NUMA IN THE PATHOGENESIS OF APL
    Pier Paolo Pandolfi; Fiscal Year: 2005
    ..The biological nature and the molecular basis underlying these genetic interactions will be analyzed in PML-/-/PLZF-/- mice and cells. ..
  2. 2005 Cancer Models and Mechanisms Gordon Conference
    Pier Paolo Pandolfi; Fiscal Year: 2005
    ..abstract_text> ..
  3. Control of Protein Translation in Cancer Pathogenesis
    Pier Paolo Pandolfi; Fiscal Year: 2008
    ..Briefly, our aims are to: i) examine in Pten mutants the role of Tscl/Tsc2, mTOR, S6K1/S6K2, 4E-BPs and elF4s in tumorigenesis; ii) asses the relevance of deregulated protein translational ..
  4. FUSION PROTEINS IN THE MOLECULAR PATHOGENESIS OF APL
    Pier Paolo Pandolfi; Fiscal Year: 2009
    ..We will determine in vivo the relevance of aberrant centrosome duplication and genetic instability in APL leukemogenesis. ..
  5. MURINE MODELS OF TSC 1: MECHANISMS AND THERAPIES
    David Kwiatkowski; Fiscal Year: 2001
    ..Two genes (TSC 1 and TSC2) cause this disorder and both have recently been identified...
  6. GELSOLIN: ROLES IN APOPTOSIS AND TUMOR DEVELOPMENT
    David Kwiatkowski; Fiscal Year: 2003
    ..The gelsolin gene defect will be bred into mice engineered or treated to have tumor predisposition: p53 null mice, Tsc2 null mice, mice treated with ENU to induce bladder tumors, and mice treated with urothane to induce lung tumors...
  7. GENOTYPING CENTER FOR INNATE IMMUNITY PGA
    David Kwiatkowski; Fiscal Year: 2004
    ..abstract_text> ..
  8. Preclinical Studies of Rapamycin for TSC Brain Disease
    David Kwiatkowski; Fiscal Year: 2006
    ..studies in cultured cells and on tumors arising in TSC patients and mouse models indicate that loss of either tuberin or hamartin leads to a molecular signature of activation of mTOR...
  9. Tuberous Sclerosis: Mutations and Murine Models
    David Kwiatkowski; Fiscal Year: 2006
    ..using multiple cell types derived from Tsc2 null mouse embryos, we will examine the biochemical function of tuberin, including analysis of rap1, rho, and PI3-kinase signaling...
  10. The Role of Tuberin in Smooth Muscle Cell Proliferation
    Geraldine Finlay; Fiscal Year: 2007
    ..Geraldine Finlay to pursue research on the influence of tuberin on the control of smooth muscle cell growth in response to estrogen...