TSC2

Summary

Gene Symbol: TSC2
Description: TSC complex subunit 2
Alias: LAM, PPP1R160, TSC4, tuberin, protein phosphatase 1, regulatory subunit 160, tuberous sclerosis 2 protein
Species: human

Top Publications

  1. pmc Insulin like growth factor-1-induced phosphorylation and altered distribution of tuberous sclerosis complex (TSC)1/TSC2 in C2C12 myotubes
    Mitsunori Miyazaki
    Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington, USA
    FEBS J 277:2180-91. 2010
  2. pmc AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation
    Junyu Ning
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27705, USA
    Mol Endocrinol 24:1218-29. 2010
  3. pmc Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway
    Sei Yoshida
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 286:32651-60. 2011
  4. ncbi Identification of a novel interaction of 14-3-3 with p190RhoGEF
    J Zhai
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 276:41318-24. 2001
  5. ncbi Identification and characterization of the interaction between tuberin and 14-3-3zeta
    Mark Nellist
    Department of Clinical Genetics, Erasmus Medisch Centrum, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
    J Biol Chem 277:39417-24. 2002
  6. ncbi The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination
    G Benvenuto
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, MD 20892, USA
    Oncogene 19:6306-16. 2000
  7. pmc Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002
  8. 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
  9. ncbi Cross-talk between tuberin, calmodulin, and estrogen signaling pathways
    Brian York
    Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536 0298, USA
    FASEB J 19:1202-4. 2005
  10. ncbi The tuberous sclerosis genes, TSC1 and TSC2, trigger different gene expression responses
    Margit Rosner
    Medical Genetics, Department of Obstetrics and Gynecology, Medical University of Vienna, A 1090 Vienna, Austria
    Int J Oncol 27:1411-24. 2005

Research Grants

  1. David M Sabatini; Fiscal Year: 2016
  2. Uterine-specific genetic modification and lymphangioleiomyomatosis
    JOSE M TEIXEIRA; Fiscal Year: 2012
  3. The Lymphangioleiomyomatosis (LAM)Genome Atlas
    DAVID J contact KWIATKOWSKI; Fiscal Year: 2010
  4. Tuberin &hamartin in rapamycin-sensitive &insensitive smooth muscle cell growth
    Usamah S Kayyali; Fiscal Year: 2013
  5. FRANCIS XAVIER MCCORMACK; Fiscal Year: 2016
  6. Tuberous Sclerosis: Mutations and Murine Models
    David J Kwiatkowski; Fiscal Year: 2013
  7. 2013 International Research Conference on Tuberous Sclerosis Complex and Related
    Steven L Roberds; Fiscal Year: 2013
  8. Regulation of Estrogen Signaling by Tuberin and Rheb
    Elizabeth P Henske; Fiscal Year: 2010
  9. Therapeutic Strategy for LAM (Lymphangioleiomyomatosis)
    TONY EISSA; Fiscal Year: 2013
  10. Tuberous Sclerosis Complex Conference: From Genes to New Therapeutics
    VICKY WHITTEMORE; Fiscal Year: 2007

Detail Information

Publications232 found, 100 shown here

  1. pmc Insulin like growth factor-1-induced phosphorylation and altered distribution of tuberous sclerosis complex (TSC)1/TSC2 in C2C12 myotubes
    Mitsunori Miyazaki
    Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington, USA
    FEBS J 277:2180-91. 2010
    ..C2C12 myotubes requires a phosphorylation-dependent, altered distribution of the tuberous sclerosis complex (TSC)1/TSC2 complex from the membrane to the cytosol...
  2. pmc AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation
    Junyu Ning
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27705, USA
    Mol Endocrinol 24:1218-29. 2010
    ..stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K)...
  3. pmc Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway
    Sei Yoshida
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 286:32651-60. 2011
    ..cellular redox potential with a cysteine oxidant or reducing agent failed to alter mTORC1 activity in TSC1(-/-) or TSC2(-/-) mouse embryonic fibroblast cells...
  4. ncbi Identification of a novel interaction of 14-3-3 with p190RhoGEF
    J Zhai
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 276:41318-24. 2001
    ..The findings suggest a potential role for 14-3-3 in modulating p190RhoGEF activity or in linking p190RhoGEF to the activities of other pathways in the neuron...
  5. ncbi Identification and characterization of the interaction between tuberin and 14-3-3zeta
    Mark Nellist
    Department of Clinical Genetics, Erasmus Medisch Centrum, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
    J Biol Chem 277:39417-24. 2002
    ..TSC1 encodes a 130-kDa protein called hamartin, and TSC2 encodes a 200-kDa protein called tuberin. Although it has been shown that hamartin and tuberin form a complex and mediate phosphoinositide 3-kinase/Akt-..
  6. ncbi The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination
    G Benvenuto
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, MD 20892, USA
    Oncogene 19:6306-16. 2000
    ..was associated with an increase in the endogenous level of the product of the tuberous sclerosis-2 (TSC2) gene, tuberin. As overexpression of tuberin inhibits cell growth, and hamartin is known to bind tuberin, these results ..
  7. pmc Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
    Andrew R Tee
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13571-6. 2002
    ..that occurs upon mutation of either the TSC1 or TSC2 genes, which encode the protein products hamartin and tuberin, respectively...
  8. 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...
  9. ncbi Cross-talk between tuberin, calmodulin, and estrogen signaling pathways
    Brian York
    Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536 0298, USA
    FASEB J 19:1202-4. 2005
    ..estrogen-mediated signaling events and mutations associated with the tuberous sclerosis complex 2 gene product tuberin. These two observations fostered the hypothesis that tuberin's impact on estrogen-mediated signaling might be ..
  10. ncbi The tuberous sclerosis genes, TSC1 and TSC2, trigger different gene expression responses
    Margit Rosner
    Medical Genetics, Department of Obstetrics and Gynecology, Medical University of Vienna, A 1090 Vienna, Austria
    Int J Oncol 27:1411-24. 2005
    ..The genes, TSC1 on chromosome 9q34, encoding hamartin, and TSC2 on chromosome 16p13.3, encoding tuberin are responsible for TSC...
  11. pmc Rapamycin-insensitive up-regulation of MMP2 and other genes in tuberous sclerosis complex 2-deficient lymphangioleiomyomatosis-like cells
    Po Shun Lee
    Pulmonary and Critical Care Division, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Am J Respir Cell Mol Biol 42:227-34. 2010
    ..The objective of this study was to investigate how tuberous sclerosis complex (TSC) 1 or TSC2 deficiency alters MMP expression and regulation...
  12. ncbi Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products
    M van Slegtenhorst
    MGC Department of Clinical Genetics, Erasmus University, 3015GE Rotterdam, The Netherlands
    Hum Mol Genet 7:1053-7. 1998
    ..TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and rab5...
  13. ncbi Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles
    T L Plank
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cancer Res 58:4766-70. 1998
    ..Tuberous sclerosis is an inherited syndrome associated with mutations in two tumor suppressor genes: TSC1 and TSC2. Tuberin, the product of TSC2, appears to be localized to the Golgi apparatus and may have a function in vesicular ..
  14. ncbi Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis
    Y Niida
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mutat 14:412-22. 1999
    ..With the cloning of two causative genes, TSC1 and TSC2 it is now possible to analyze both genes in TSC patients and identify germline mutations...
  15. ncbi Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin
    M Nellist
    Department of Clinical Genetics, Erasmus University, 3015 GE Rotterdam, The Netherlands
    J Biol Chem 274:35647-52. 1999
    ..Analysis of the amino acid sequence of tuberin, the 200-kDa product of the TSC2 gene, identified a region with limited homology to GTPase-activating proteins...
  16. pmc Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis
    T Carsillo
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia PA 19111, USA
    Proc Natl Acad Sci U S A 97:6085-90. 2000
    ..We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC ..
  17. pmc Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs
    S L Dabora
    Genetics Laboratory, Division of Hematology, Brigham and Women s Hospital, Boston, MA, 02115, USA
    Am J Hum Genet 68:64-80. 2001
    ..sclerosis (TSC) is a relatively common hamartoma syndrome caused by mutations in either of two genes, TSC1 and TSC2. Here we report comprehensive mutation analysis in 224 index patients with TSC and correlate mutation findings with ..
  18. ncbi The tuberous sclerosis 2 gene product can localize to nuclei in a phosphorylation-dependent manner
    D Lou
    Department of Biochemistry, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA
    Mol Cell Biol Res Commun 4:374-80. 2001
    The tuberous sclerosis 2 (TSC2) gene has been genetically mapped to a disease characterized by abnormal cell proliferation that results in the production of tumorous lesions in a variety of tissues...
  19. 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...
  20. 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...
  21. ncbi Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin
    Han C Dan
    Department of Pathology, Molecular Oncology, and Drug Discovery Programs, University of South Florida College of Medicine, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
    J Biol Chem 277:35364-70. 2002
    Normal cellular functions of hamartin and tuberin, encoded by the TSC1 and TSC2 tumor suppressor genes, are closely related to their direct interactions...
  22. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
    ..Mutation in either the TSC1 or TSC2 tumour suppressor gene is responsible for both the familial and sporadic forms of this disease...
  23. ncbi 14-3-3 interacts with the tumor suppressor tuberin at Akt phosphorylation site(s)
    Matt Y Liu
    Department of Carcinogenesis, Science Park Research Division, The University of Texas M D Anderson Cancer Center, Smithville, Texas 78957, USA
    Cancer Res 62:6475-80. 2002
    b>Tuberin, the product of the tuberous sclerosis complex 2 tumor suppressor gene, is a phosphoprotein that negatively regulates phosphatidylinositol 3'-kinase signaling downstream of Akt...
  24. ncbi The tuberin-hamartin complex negatively regulates beta-catenin signaling activity
    Baldwin C Mak
    Department of Surgery, University of Washington, School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 278:5947-51. 2003
    ..Their protein products, hamartin and tuberin, respectively, form a functional complex that affects cell growth, differentiation, and proliferation...
  25. ncbi Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours
    M A Knowles
    Cancer Research UK Clinical Centre, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK
    Biochem Soc Trans 31:597-602. 2003
    In tuberous sclerosis patients, inactivation of the tuberous sclerosis complex tumour-suppressor genes TSC1 and TSC2 contributes to the development of a wide range of hamartomatous lesions...
  26. ncbi Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2
    Attila Garami
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Mol Cell 11:1457-66. 2003
    ..Finally, coexpression of a human TSC2 cDNA harboring a disease-associated point mutation in the GAP domain, failed to stimulate Rheb GTPase activity or ..
  27. ncbi Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner
    Ariel F Castro
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Cancer Institute, Indianapolis, Indiana 46202, USA
    J Biol Chem 278:32493-6. 2003
    Recently the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product has been identified as a negative regulator of protein synthesis upstream of the mTOR and ribosomal S6 kinases...
  28. pmc Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Genes Dev 17:1829-34. 2003
    Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1...
  29. 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...
  30. ncbi Estrogen-induced smooth muscle cell growth is regulated by tuberin and associated with altered activation of platelet-derived growth factor receptor-beta and ERK-1/2
    Geraldine A Finlay
    Pulmonary and Critical Care Division, Department of Medicine, Tupper Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    J Biol Chem 279:23114-22. 2004
    ..We hypothesized that tuberin, the protein product of TSC2, binds to estrogen receptors (ER) and regulates the growth effect of E2...
  31. ncbi Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent
    Magdalena Karbowniczek
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 279:29930-7. 2004
    ..The products of the TSC1 and TSC2 genes, hamartin and tuberin, respectively, heterodimerize and inhibit the mammalian target of rapamycin (mTOR)...
  32. ncbi Upstream and downstream of mTOR
    Nissim Hay
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 60607, USA
    Genes Dev 18:1926-45. 2004
    ..We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity...
  33. pmc Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity
    Yong Li
    Life Sciences Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor 48109 0606, USA
    Mol Cell Biol 24:7965-75. 2004
    Tuberous sclerosis complex (TSC) is a genetic disease caused by a mutation in either the tsc1 or tsc2 tumor suppressor gene...
  34. pmc Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase
    Philippe P Roux
    Department of Cell Biology and Taplin Biological Mass Spectrometry Facility, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:13489-94. 2004
    ..disorder caused by mutations in either of the two tumor suppressor genes TSC1 or TSC2, which encode hamartin and tuberin, respectively...
  35. pmc Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors
    Bryan A Ballif
    Department of Cell Biology and Taplin Biological Mass Spectrometry Facility, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:667-72. 2005
    ..the ERK/p90 ribosomal S6 kinase-signaling targets, the tuberous sclerosis complex (TSC) tumor suppressors TSC1 and TSC2. By using quantitative phosphorylation profiling in conjunction with pharmacological kinase inhibitors we uncovered ..
  36. ncbi Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex
    Ozgur Sancak
    Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
    Eur J Hum Genet 13:731-41. 2005
    ..TSC is caused by mutations in either the TSC1 or TSC2 gene...
  37. 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)...
  38. pmc Isolation and growth of smooth muscle-like cells derived from tuberous sclerosis complex-2 human renal angiomyolipoma: epidermal growth factor is the required growth factor
    Elena Lesma
    Laboratory of Pharmacology, Faculty of Medicine, University of Milan, Milan, Italy
    Am J Pathol 167:1093-103. 2005
    Tuberous sclerosis complex (TSC) is a tumor suppressor gene disorder characterized by mutations in the TSC1 or TSC2 genes...
  39. pmc Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning
    Sheng Li Cai
    Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, 78957, USA
    J Cell Biol 173:279-89. 2006
    Loss of tuberin, the product of TSC2 gene, increases mammalian target of rapamycin (mTOR) signaling, promoting cell growth and tumor development...
  40. ncbi Subcellular distribution of the TSC2 gene product tuberin in human airway smooth muscle cells is driven by multiple localization sequences and is cell-cycle dependent
    Debbie Clements
    Division of Therapeutics and Molecular Medicine, University of Nottingham, Queens Medical Centre, University Hospital, Nottingham NG7 2UH, UK
    Am J Physiol Lung Cell Mol Physiol 292:L258-66. 2007
    The products of the tuberous sclerosis complex (TSC) genes, hamartin and tuberin (TSC1 and 2), form a heteromer, which represses the kinase mammalian target of rapamycin...
  41. ncbi TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 126:955-68. 2006
    Mutation in the TSC2 tumor suppressor causes tuberous sclerosis complex, a disease characterized by hamartoma formation in multiple tissues...
  42. ncbi Tuberin nuclear localization can be regulated by phosphorylation of its carboxyl terminus
    Brian York
    Department of Molecular and Cellular Biochemistry, University of Kentucky, 741 South Limestone Avenue, Lexington, KY 40536, USA
    Mol Cancer Res 4:885-97. 2006
    b>Tuberin, the tuberous sclerosis 2 (TSC2) gene product, has been identified as a tumor suppressor protein genetically implicated in the pathology of tuberous sclerosis and the female-specific lung disease lymphangioleiomyomatosis...
  43. ncbi Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations
    Piotr Kozlowski
    Genetics Laboratory, Division of Translational Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Hum Genet 121:389-400. 2007
    Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by mutations in either of two genes, TSC1 and TSC2. Point mutations and small indels account for most TSC1 and TSC2 mutations...
  44. ncbi Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States
    Kit Sing Au
    Department of Pediatrics, The University of Texas Medical School at Houston, 77030, USA
    Genet Med 9:88-100. 2007
    ..72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified...
  45. pmc Survivin expression in tuberous sclerosis complex cells
    Stephana Carelli
    Laboratory of Pharmacology, Department of Medicine, Surgery and Dentistry, University of Milan, Polo H San Paolo, Milano, Italy
    Mol Med 13:166-77. 2007
    Tuberous Sclerosis Complex (TSC) is a tumor suppressor gene disorder with mutations of TSC1/TSC2 genes. This leads to the development of hamartomas that most frequently affect central nervous system, kidney, and skin...
  46. ncbi IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway
    Dung Fang Lee
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cell 130:440-55. 2007
    ..The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function ..
  47. ncbi Tuberin regulates the DNA repair enzyme OGG1
    Samy L Habib
    George O Brien Kidney Research Center, Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA
    Am J Physiol Renal Physiol 294:F281-90. 2008
    ..The TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas...
  48. ncbi Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma
    C C Pan
    Department of Pathology, Taipei Veterans General Hospital and National Yang Ming University, Taiwan
    J Pathol 214:387-93. 2008
    ..study of PEComas demonstrated recurrent chromosomal aberrations including deletions on chromosome 16p, where the TSC2 gene is located. In this study, we focused on the alteration of chromosome 16p, including TSC2...
  49. 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,..
  50. 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...
  51. pmc Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma
    Sanjukta Chakraborty
    Department of Molecular Reproduction Development and Genetics, Indian Institute of Science, Bangalore, India
    BMC Cancer 8:163. 2008
    ..However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC.
  52. pmc Anti-EGFR antibody efficiently and specifically inhibits human TSC2-/- smooth muscle cell proliferation. Possible treatment options for TSC and LAM
    Elena Lesma
    Laboratory of Pharmacology, Department of Medicine, Surgery and Dentistry Polo H San Paolo, Faculty of Medicine, University of Milan, Milan, Italy
    PLoS ONE 3:e3558. 2008
    ..cells (TSC2(-/-) ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2(-/-) ASM cell proliferation is EGF-dependent.
  53. pmc The methylation of the TSC2 promoter underlies the abnormal growth of TSC2 angiomyolipoma-derived smooth muscle cells
    Elena Lesma
    Laboratory of Pharmacology, Dept of Medicine, Surgery, and Dentistry, Via A Di Rudini 8, 20142 Milano, Italy
    Am J Pathol 174:2150-9. 2009
    ..Smooth muscle-like cells (ASMs) were isolated from an angiomyolipoma of a patient with TSC. These cells lacked tuberin, were labeled by both HMB45 and CD44v6 antibodies, and had constitutive S6 phosphorylation...
  54. pmc The tuberous sclerosis complex
    Ksenia A Orlova
    Departments of Neurology and Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Ann N Y Acad Sci 1184:87-105. 2010
    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems...
  55. pmc Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis
    Nicole A Neuman
    Division of Pulmonary and Critical Care Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    EMBO Mol Med 3:189-200. 2011
    The protein products of the tuberous sclerosis complex (TSC) genes, TSC1 and TSC2, form a complex, which inhibits the small G-protein, Ras homolog enriched in brain (Rheb)...
  56. ncbi Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity
    R Wienecke
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892 4040, USA
    J Biol Chem 270:16409-14. 1995
    ..The putative TSC2 product (tuberin) contains a region of limited homology to the catalytic domain of Rap1GAP...
  57. ncbi Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis
    A C Jones
    Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, UK
    Hum Mol Genet 6:2155-61. 1997
    ..TSC exhibits locus heterogeneity: the TSC2 gene is located at 16p13...
  58. pmc Germ-line mutational analysis of the TSC2 gene in 90 tuberous-sclerosis patients
    K S Au
    Department of Pediatrics, University of Texas Medical School, Houston, TX 77030, USA
    Am J Hum Genet 62:286-94. 1998
    ..protein (GAP)-related domains of TSC2 or in the activating domains that have been identified in rat tuberin. We did not detect any mutations in the exons (25 and 31) that are spliced out in the isoforms...
  59. pmc Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis
    A C Jones
    Institute of Medical Genetics, University of Wales College of Medicine, Cardiff CF4 4XN, United Kingdom
    Am J Hum Genet 64:1305-15. 1999
    ..TSC is caused by mutations affecting either of the presumed tumor-suppressor genes, TSC1 and TSC2. Both appear to function as tumor suppressors, because somatic loss or intragenic mutation of the corresponding ..
  60. ncbi Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin
    A K Hodges
    Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
    Hum Mol Genet 10:2899-905. 2001
    Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely to be closely linked...
  61. ncbi Regulation of TSC2 by 14-3-3 binding
    Yong Li
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 277:44593-6. 2002
    Mutation in either the TSC1 or TSC2 tumor suppressor gene is responsible for the inherited genetic disease of tuberous sclerosis complex. TSC1 and TSC2 form a physical and functional complex to regulate cell growth...
  62. ncbi The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 gene product, and enhances its interaction with 14-3-3
    Yong Li
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109, USA
    J Biol Chem 278:13663-71. 2003
    ..TSC1 and TSC2 (also known as hamartin and tuberin, respectively) form a functional complex and negatively regulate cell growth by inhibiting protein synthesis...
  63. ncbi Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma
    Nisreen El-Hashemite
    Brigham and Women Hospital, Department of Medicine, Haematology Division, Boston MA 02115, USA
    Lancet 361:1348-9. 2003
    ..Hamartin (encoded by TSC1) and S6K was expressed in all samples. Tuberin (TSC2) was weak or absent in angiomyolipomas, but present in healthy kidney, whereas, phosphorylated p70 S6 ..
  64. ncbi Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B
    Aristotelis Astrinidis
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 278:51372-9. 2003
    ..Hamartin and tuberin, the products of the TSC1 and TSC2 genes, respectively, form a complex and inhibit signaling by the mammalian ..
  65. 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...
  66. ncbi Phosphorylation of tuberin as a novel mechanism for somatic inactivation of the tuberous sclerosis complex proteins in brain lesions
    Sangyeul Han
    Molecular Neurogenetics Unit, Molecular Neuro Oncology, and Department of Neurology, Harvard Medical School Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Cancer Res 64:812-6. 2004
    ..We demonstrate a novel mechanism of post-translational inactivation of the TSC2 protein, tuberin, by physiologically inappropriate phosphorylation, which is specific to tuberous sclerosis complex-associated ..
  67. ncbi Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation
    Jennifer A Chan
    Division of Neuropathology, Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Neuropathol Exp Neurol 63:1236-42. 2004
    ..of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex...
  68. ncbi Clinical symptoms of tuberous sclerosis complex in patients with an identical TSC2 mutation
    Paulina Rok
    Department of Child Neurology and Epileptology, The Children s Memorial Health Institute, Warsaw, Poland
    Med Sci Monit 11:CR230-234. 2005
    ..TSC is caused by mutations in either of two tumor suppressor genes: TSC1 or TSC2. The aim of this study was to analyze the clinical picture of TSC in patients with an identical TSC2 mutation...
  69. ncbi Expression and prognostic value of tuberous sclerosis complex 2 gene product tuberin in human pancreatic cancer
    Kozo Kataoka
    Department of Surgery and Basic Surgical Science, Kyoto University, Japan
    Surgery 138:450-5. 2005
    ..disorder caused by mutation of either of 2 tumor suppressor genes, TSC1 or TSC2, which encode hamartin and tuberin, respectively...
  70. ncbi Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner
    Aristotelis Astrinidis
    Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Hum Mol Genet 15:287-97. 2006
    ..Hamartin and tuberin, the products of TSC1 and TSC2, respectively, form heterodimers and inhibit the mammalian target of rapamycin...
  71. pmc Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2
    Elena A Goncharova
    Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, 421 Curie Boulevard, BRB II III, Philadelphia, PA 19104 6160, USA
    Am J Respir Cell Mol Biol 34:561-72. 2006
    The TSC1 and TSC2 proteins, which function as a TSC1/TSC2 tumor suppressor complex, are associated with lymphangioleiomyomatosis (LAM), a genetic disorder characterized by the abnormal growth of smooth muscle-like cells in the lungs...
  72. 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...
  73. doi Tuberous sclerosis complex: disease modifiers and treatments
    Kit Sing Au
    Division of Medical Genetics, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas, USA
    Curr Opin Pediatr 20:628-33. 2008
    ..The two causative genes, TSC1 and TSC2, which code for hamartin and tuberin respectively, play central roles in regulating cell survival and proliferation signaling pathways...
  74. ncbi 14-3-3beta binds to and negatively regulates the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product, tuberin
    Stuart D Shumway
    Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, 27599 7295, USA
    J Biol Chem 278:2089-92. 2003
    TSC2, or tuberin, is the product of the tuberous sclerosis tumor suppressor gene TSC2 and acts downstream of the phosphatidylinositol 3-kinase-Akt signaling pathway to negatively regulate cellular growth...
  75. ncbi Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins
    Sarah E M Meek
    Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA
    J Biol Chem 279:32046-54. 2004
    ..This study adds to the growing list of human 14-3-3-binding proteins and implicates a role for 14-3-3 proteins in a plethora of essential biological processes...
  76. ncbi Analysis of a polymorphism in the tuberous sclerosis (TSC2) gene does not predispose to schizophrenia
    R Przkora
    Department of Neuropathology, University of Bonn Medical Center, Germany
    Eur Arch Psychiatry Clin Neurosci 248:314-5. 1998
    ..A polymorphism in the TSC2 gene has been found to be increased in gangliogliomas, a lesion which is associated with disturbed neuro-glial cell ..
  77. ncbi Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature
    Andrew L Folpe
    Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
    Am J Surg Pathol 29:1558-75. 2005
    ..of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations...
  78. pmc Utility of [18F]2-fluoro-2-deoxyglucose-PET in sporadic and tuberous sclerosis-associated lymphangioleiomyomatosis
    Lisa R Young
    Department of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Chest 136:926-33. 2009
    ..perivascular epithelioid cell tumors (PEComas), including angiomyolipomas (AMLs) and lymphangioleiomyomatosis (LAM)...
  79. pmc Renal and liver tumors in Tsc2(+/-) mice, a model of tuberous sclerosis complex, do not respond to treatment with atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
    Geraldine A Finlay
    Pulmonary and Critical Care Division, Tufts Medical Center, Boston, MA 02111, USA
    Mol Cancer Ther 8:1799-807. 2009
    Inactivating mutations of the tumor suppressor gene TSC2 are associated with tumorigenesis in tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis...
  80. ncbi Multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis with a TSC2 gene
    H Maruyama
    Department of Pathology, Hoshigaoka Koseinenkin Hospital, Hirakata, Japan
    Mod Pathol 14:609-14. 2001
    ..Such LAM showed positive immunoreactivity for HMB-45 (a monoclonal antibody specific for human melanoma) and tuberin (the gene product of TSC2)...
  81. doi Lymphangioleiomyomatosis: a clinical update
    Francis X McCormack
    Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati, MSB 6053, 231 Albert Sabin Way, Cincinnati, OH 45267 0564, USA
    Chest 133:507-16. 2008
    Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that is associated with mutations in tuberous sclerosis genes, renal angiomyolipomas, lymphatic spread, and remarkable female gender restriction...
  82. 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 ..
  83. pmc CT of sclerotic bone lesions: imaging features differentiating tuberous sclerosis complex with lymphangioleiomyomatosis from sporadic lymphangioleiomymatosis
    Nilo A Avila
    Radiology Service, Washington D C Veterans Affairs Medical Center, 50 Irving St NW, Room BH 223, Washington, DC 20422, USA
    Radiology 254:851-7. 2010
    ..if sclerotic bone lesions evident at body computed tomography (CT) are of value as a diagnostic criterion of tuberous sclerosis complex (TSC) and in the differentiation of TSC with lymphangioleiomyomatosis (LAM) from sporadic LAM.
  84. doi Lymphangioleiomyomatosis and tuberous sclerosis complex
    Dimitrios Chorianopoulos
    1st Department of Respiratory Medicine, University of Athens Medical School, Sotiria General Hospital, Athens, Greece
    Lung 186:197-207. 2008
    ..Both of these genes are tumor suppressor genes encoding hamartin (TSC1) and tuberin (TSC2)...
  85. ncbi Selective inhibition of growth of tuberous sclerosis complex 2 null cells by atorvastatin is associated with impaired Rheb and Rho GTPase function and reduced mTOR/S6 kinase activity
    Geraldine A Finlay
    Pulmonary and Critical Care Division, Department of Medicine, Tupper Research Institute, Tufts New England Medical Center, Boston, MA 02111, USA
    Cancer Res 67:9878-86. 2007
    Inactivating mutations in the tuberous sclerosis complex 2 (TSC2) gene, which encodes tuberin, result in the development of TSC and lymphangioleiomyomatosis (LAM)...
  86. pmc Tuberin regulates E-cadherin localization: implications in epithelial-mesenchymal transition
    Elizabeth A Barnes
    Department of Surgery, University of Washington, Seattle, Washington 98195, USA
    Am J Pathol 177:1765-78. 2010
    The tuberous sclerosis complex 2 (TSC2) gene encodes the protein tuberin, which functions as a key negative regulator of both mammalian target of rapamycin (mTOR) C1-dependent cell growth and proliferation...
  87. ncbi Pathogenesis of multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis and association with tuberous sclerosis genes TSC1 and TSC2
    H Maruyama
    Department of Pathology, Hoshigaoka Koseinenkin Hospital, 8 1, 4 chome Hoshigaoka, Hirakata, Osaka 573 8511, Japan
    Pathol Int 51:585-94. 2001
    ..b>Tuberin, the TSC2 gene product, has recently been found to be expressed in LAM and MMPH...
  88. doi Therapeutic targeting of mTOR in tuberous sclerosis
    Julian R Sampson
    Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    Biochem Soc Trans 37:259-64. 2009
    ..Both diseases are caused by mutations of TSC1 or TSC2 (TSC is tuberous sclerosis complex) that impair GAP (GTPase-activating protein) activity of the TSC1-TSC2 complex ..
  89. 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...
  90. pmc Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors
    Chelsey Woodrum
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Karp Building, Boston, MA, USA
    J Transl Med 8:14. 2010
    ..Mouse models of TSC2 related tumors are useful for evaluating new approaches to drug therapy for TSC.
  91. ncbi [The results of recent research in neurocutaneous syndromes]
    K Ohno
    Department of Neurobiology, School of Life Sciences, Tottori University Faculty of Medicine, Yonago
    No To Hattatsu 30:109-14. 1998
    Identification of NF1, TSC2 and TSC1 genes has enabled us to focus on their function and regulation. Evidence suggests that these genes are tumor suppressor genes...
  92. pmc MCP-1 overexpressed in tuberous sclerosis lesions acts as a paracrine factor for tumor development
    Shaowei Li
    Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Exp Med 202:617-24. 2005
    ..TSC) develop hamartomatous tumors showing loss of function of the tumor suppressor TSC1 (hamartin) or TSC2 (tuberin) and increased angiogenesis, fibrosis, and abundant mononuclear phagocytes...
  93. 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...
  94. pmc Tuberous sclerosis preclinical studies: timing of treatment, combination of a rapamycin analog (CCI-779) and interferon-gamma, and comparison of rapamycin to CCI-779
    Michael P Messina
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Karp Family Research Laboratories, Boston, MA, USA
    BMC Pharmacol 7:14. 2007
    ..TSC is caused by a mutation in either the TSC1 or TSC2 genes, whose products, hamartin and tuberin, function as negative regulators in the highly-conserved mammalian target of rapamycin (mTOR) signaling pathway...
  95. doi The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners
    Margit Rosner
    Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Wahringer Gurtel 18 20, Vienna, Austria
    Mutat Res 658:234-46. 2008
    Mutations in the tumor suppressor genes TSC1 and TSC2, encoding hamartin and tuberin, respectively, cause the tumor syndrome tuberous sclerosis with similar phenotypes...
  96. 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 ..
  97. pmc Biallelic TSC gene inactivation in tuberous sclerosis complex
    Peter B Crino
    Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neurology 74:1716-23. 2010
    ..developmental question is whether tubers in tuberous sclerosis complex (TSC) form by germline and somatic TSC1 or TSC2 gene mutations...
  98. pmc Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells
    Samy L Habib
    Department of Geriatrics, Geriatric Research, Education, and Clinical Center, South Texas Veterans Healthcare System, San Antonio, TX 78229, USA
    Carcinogenesis 31:2022-30. 2010
    b>Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in tumour kidney of tuberous sclerosis complex (TSC) patients...
  99. 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...
  100. ncbi Localization of tuberous sclerosis 2 mRNA and its protein product tuberin in normal human brain and in cerebral lesions of patients with tuberous sclerosis
    C Kerfoot
    Department of Pathology and Laboratory Medicine Neuropathology, UCLA Medical Center 90095, USA
    Brain Pathol 6:367-75. 1996
    ..3. TSC2 has been cloned, sequenced and encodes a protein (tuberin) which functions as a tumor suppressor...

Research Grants76

  1. David M Sabatini; Fiscal Year: 2016
    ..Many cancer-promoting lesions activate the mTORC1 pathway. Most notably, the TSC1-TSC2 tumor suppressor complex--whose inactivation causes Tuberous Sclerosis Complex (TSC) and the related disease ..
  2. Uterine-specific genetic modification and lymphangioleiomyomatosis
    JOSE M TEIXEIRA; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Lymphangioleiomyomatosis (LAM) is a rare disease primarily found in females and is characterized by a diffuse interstitial infiltrate of atypical smooth muscle cell lesions in the lung parenchyma ..
  3. The Lymphangioleiomyomatosis (LAM)Genome Atlas
    DAVID J contact KWIATKOWSKI; Fiscal Year: 2010
    ..The second key objective is to determine the frequency of somatic point and genomic mutations in TSC1 and TSC2 in sporadic LAM, and to determine whether activating mutations in Rheb are associated with sporadic LAM...
  4. Tuberin &hamartin in rapamycin-sensitive &insensitive smooth muscle cell growth
    Usamah S Kayyali; Fiscal Year: 2013
    ..Hamartin and tuberin are highly expressed in smooth muscle and are encoded by the tumor suppressor genes, Tuberous Sclerosis Complex-1 ..
  5. FRANCIS XAVIER MCCORMACK; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The LAM Foundation 2013 Lymphangioleiomyomatosis International Research Conference will focus on the molecular mechanisms of smooth muscle proliferation and cystic lung destruction that occur in the ..
  6. Tuberous Sclerosis: Mutations and Murine Models
    David J Kwiatkowski; Fiscal Year: 2013
    ..Two genes cause TSC: TSC1 and TSC2, each of which sustains inactivating mutations that lead to disease pathogenesis through a two hit, tumor ..
  7. 2013 International Research Conference on Tuberous Sclerosis Complex and Related
    Steven L Roberds; Fiscal Year: 2013
    ..by tuberous sclerosis complex (TSC) and related disorders, including autism, epilepsy, lymphangioleiomyomatosis (LAM), cancer, and rare diseases with overlapping phenotypes...
  8. Regulation of Estrogen Signaling by Tuberin and Rheb
    Elizabeth P Henske; Fiscal Year: 2010
    This proposal is focused on the mechanisms through which the tuberous sclerosis complex (TSC) proteins, tuberin and hamartin, repress estrogen-mediated signals...
  9. Therapeutic Strategy for LAM (Lymphangioleiomyomatosis)
    TONY EISSA; Fiscal Year: 2013
    ..complex (TSC) is an autosomal dominant disorder caused by mutations in tuberous sclerosis complex 1 (TSC1) or TSC2. TSC is characterized by tumors in wide range of tissues, seizures, mental retardation, autism, and organ failure...
  10. Tuberous Sclerosis Complex Conference: From Genes to New Therapeutics
    VICKY WHITTEMORE; Fiscal Year: 2007
    ..in hamartomas and cancer Discuss the role of TSC signaling in pulmonary (specifically lymphangioleiomyomatosis, or LAM) and renal diseases (specifically, polycystic kidney disease, or PKD) Discuss the role of TSC signaling in the ..
  11. MOLECULAR BASIS OF LYMPHANGIOMYOMATOSIS
    ELIZABETH HENSKE; Fiscal Year: 2006
    ..Our preliminary data indicate that tuberin (the TSC2 gene product) also activates Rho and regulates cell adhesion and migration...
  12. CNS Manifestations of Tuberous Sclerosis Complex
    VICKY WHITTEMORE; Fiscal Year: 2005
    ..The basic biology of LAM indicates that the TSC2, and perhaps the TSC1 gene, play a significant role in LAM, so the last two LAMposiums have included numerous ..
  13. SECRETION AND BIOSYNTHESIS OF INSULIN
    Michael L McDaniel; Fiscal Year: 2012
    ..studies have determined that inhibition of glycogen synthase kinase-3 (GSK-3) &tuberous sclerosis complex 2 (TSC2) are required for mTOR activation...
  14. Interactions Between p90 Ribosomal S6 Kinase and Protein Kinase A
    Tarun B Patel; Fiscal Year: 2010
    ..with a resultant increase in phosphorylation of the cytosolic RSK1 substrates tuberous sclerosis complex 2 (TSC2) and BAD...
  15. Vera P Krymskaya; Fiscal Year: 2015
    ..for lung cell survival by acting within 5'-AMP-activated protein kinase (AMPK) - tuberous sclerosis complex 2 (TSC2) - mammalian target of rapamycin complex 2 (mTORC2) signaling pathway...
  16. Angelique Bordey; Fiscal Year: 2016
    ..TSC is caused by mutations in TSC1 or TSC2 leading to mTOR hyperactivity and developmental malformations associated with seizures and worsening of cognitive ..
  17. SAMY LEWIZ HABIB; Fiscal Year: 2016
    ..genes involved in renal carcinogenesis is tuberous sclerosis gene (TSC2), which encodes tumor suppressor protein, tuberin. Eker rats harboring mutations in TSC2 develop spontaneous renal tumors at a very high incidence...
  18. David E Cohen; Fiscal Year: 2016
    ..limits insulin signaling by binding thioesterase superfamily member 2 (Them2) and tuberous sclerosis complex 2 (TSC2)...
  19. Onanong Chivatakarn; Fiscal Year: 2014
    ..The central hypothesis is that TSC1, in conjunction with TSC2, negatively regulates the mTOR pathway downstream of ephrin/Eph in developing MNs...
  20. Regulation of Hepatic Glucose Homeostasis by Phosphatidylcholine Transfer Protein
    Baran Ersoy; Fiscal Year: 2012
    ..a regulatory complex together with thioesterase superfamily member 2 (THEM2) and tuberous sclerosis complex 2 (TSC2), which modulates insulin signaling potentialy via endoplasmic reticulum (ER) stress...
  21. Structural consequences of TSC gene mutations in brain
    Peter B Crino; Fiscal Year: 2012
    Tuberous sclerosis complex (TSC) is an autosomal disorder resulting from mutations in the TSC1 or TSC2 genes that is associated with epilepsy, cognitive disability, and autism...
  22. Kevin C Ess; Fiscal Year: 2016
    ..provided by applicant): Tuberous Sclerosis Complex (TSC) is a genetic disease caused by mutation of the TSC1 or TSC2 genes. Patients frequently have severe CNS manifestations including epilepsy, intellectual disabilities and autism...
  23. Summit on Drug Discovery in Tuberous Sclerosis Complex and Related Disorders
    Elizabeth P Henske; Fiscal Year: 2011
    ..utilized for future clinical trials for TSC and related disorders " Review efforts to identify biomarkers for TSC, LAM and related disorders that can be used as measures of disease progression and/or treatment efficacy...
  24. Pathogenesis of TSC2-Related Tumors
    Raymond Yeung; Fiscal Year: 2012
    ..In cells lacking hamartin or tuberin, products of TSC1 and TSC2, certain plasma membrane proteins are mislocalized in the cytosol secondary to a ..
  25. JONATHAN OREN LIPTON; Fiscal Year: 2016
    ..TSC is a neurogenetic syndrome that results from mutations in either the Tsc1 or Tsc2 genes that cause epilepsy, intellectual disability, and autism...
  26. Allelic Expression Imbalance in Tuberous Sclerosis Complex
    Vinodh Narayanan; Fiscal Year: 2009
    ..complex (TSC) is an autosomal dominant neurogenetic disorder caused by defects in one of two genes, TSC1 or TSC2. Neurological symptoms (seizures, mental retardation, autistic features) are the most disabling problem and are ..
  27. High Resolution Mass Spectrometry System
    John M Asara; Fiscal Year: 2012
    ..anemia, (4) Elucidation of the functional role of the tuberous sclerosis complex (TSC) tumor suppressors (TSC1 and TSC2) effects on the TORC complexes and (5) Proteomics characterization of Alzheimer's Disease brain plaques...
  28. Harry Chugani; Fiscal Year: 2014
    ..TSC is an autosomal dominant inherited disorder resulting from mutations in at least two different genes, TSC1 and TSC2. Patients with TSC manifest various phenotypes associated with lesions in brain, retina, heart, kidney, lung, liver ..
  29. Synaptic Plasticity, Memory and Social Behavior
    ITZAMARIE CHEVERE TORRES; Fiscal Year: 2010
    ..At the molecular level, mutations of the tumor suppressor genes harmatin and tuberin, also known as tsc1 and tsc2, respectively, have been identified as the cause of TSC...
  30. The Mechanism of Excess Neural Crest-Derived Craniofacial Bone Formation in a Mou
    Fei Liu; Fiscal Year: 2012
    ..of benign congenital tumors in multiple organs and is caused by mutations in one of two genes, called TSC1 and TSC2. Osseous lesions in TSC are characterized by osteosclerotic changes in skeletal and craniofacial bones...
  31. David J Kwiatkowski; Fiscal Year: 2016
    ..each of these genes is also involved in the development of typical adult malignancies: TSC1 - bladder carcinoma;TSC2 - PEComas pancreatic neuroendocrine tumors, and bladder cancer;PTEN - many adult cancers, including breast, lung, ..
  32. Kun Liang Guan; Fiscal Year: 2015
    ..Recent studies have elucidated a conserved signaling pathway consisting of TSC1/TSC2-Rheb-mTOR. TSC1 and TSC2 are two tumor suppressor genes mutated in the tuberous sclerosis...
  33. mTOR signaling and sporadic chordomas
    Sangyeul Han; Fiscal Year: 2010
    ..TSC proteins tuberin and hamartin function together to inhibit mammalian target of rapamycin (mTOR) pathway, a key regulator of ..
  34. The In Vivo Role of JNK-1 and IRS-1 Ser307 Phosphorylation In Development of Insu
    Umut Ozcan; Fiscal Year: 2012
    ..Tuberous sclerosis complex 1 and 2 (TSC1 and 2) genes both encode tumor suppressors. TSC1 and TSC2 are associated in a complex such that deficiency of either gene disrupts the function of this complex, and leads to ..
  35. The Role of FKBP38 in tumorigenesis associated with Tsc deficiency
    Yu Jiang; Fiscal Year: 2012
    ..The gene products of TSC1 and TSC2, hamartin and tuberin, form a complex that negatively regulates Rheb, a Ras-like small GTP binding protein...
  36. Elizabeth P Henske; Fiscal Year: 2016
    ..In Aims 1 and 2, we will test the hypothesis that low levels of autophagy in TSC2-deficient cells lead to a "metabolic starvation" phenotype, making TSC2-deficient cells hypersensitive to further ..
  37. Robert P Carson; Fiscal Year: 2016
    ..and decreased mTORC2 activity are seen in TSC, we will utilize a genetic approach to independently target the Tsc2 gene, resulting in increased mTORC1 activity and decreased mTORC2 activity, and the Rictor gene, resulting in just ..
  38. Hancai Dan; Fiscal Year: 2015
    ..TSC is caused by mutation in either the TSC1 or TSC2 gene...
  39. The Role of IKK and NF-kappaB in Controlling mTOR Signaling and TSC Progression
    Hancai Dan; Fiscal Year: 2012
    ..TSC is caused by mutation in either the TSC1 or TSC2 gene...
  40. Role of TSC Proteins in Neuronal Polarity and Axon Guidance
    Mustafa Sahin; Fiscal Year: 2010
    ..Furthermore, we find that in mice lacking Tsc2, topographic mapping of connections in the brain are aberrant compared to wild-type mice...
  41. Role of Perinatal Neuronal Stem Cells in Tuber Formation
    DAVID MATTHEW FELICIANO; Fiscal Year: 2013
    ..Inactivating mutations in one of two tumor suppressor genes, TSC1 and TSC2, which encode hamartin and tuberin respectively, are thought to underlie the neurological lesions associated with TSC...
  42. Cheryl L Walker; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The Tuberous Sclerosis Complex 2 (TSC2) tumor suppressor functions as a gatekeeper for mTOR activity in the PI3K signaling pathway...
  43. Thomas N Darling; Fiscal Year: 2016
    ..b>TSC2 is a protein that inhibits mTORC1 and other growth signaling pathways, and it appears to regulate hair follicle ..
  44. Roles of Tuberin (TSC2), Hamartin (TSC1), and Rheb in Renal Cyst Pathogenesis
    Elizabeth P Henske; Fiscal Year: 2010
    ..TSC) is caused by germline inactivating mutations in the TSC1 or TSC2 genes, which encode hamartin (TSC1) and tuberin (TSC2), respectively. Both humans and mice with mutations in TSC1 or TSC2 can develop cystic kidney disease...
  45. Peter T Tsai; Fiscal Year: 2016
    ..Tuberous Sclerosis Complex, a genetic disorder caused by mutation in either Tsc1 or Tsc2, has high rates of autism (~50%)...
  46. Regulation of the mTOR Pathway by Hypoxia and the REDD1 Protein
    James Brugarolas; Fiscal Year: 2012
    ..factors and energy stores are relayed to mTORC1 through the tuberous sclerosis complex proteins 1 (TSC1) and 2 (TSC2), which form a complex (TSC1/TSC2) with tumor suppressor function...
  47. Elucidating the Roles of SHANK3 and FXR in the Autism Interactome
    Huda Y Zoghbi; Fiscal Year: 2010
    ..Fragile X protein (FMRP) and its paralogs (FXR1 and 2) as well as the tuberous sclerosis complex proteins (TSC1 and TSC2)...
  48. Vera P Krymskaya; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Pulmonary LAM, a rare lung disease affecting predominantly women of childbearing age, is associated with mutations of the Tuberous Sclerosis Complex (TSC) tumor suppressor genes...
  49. An RNAi Screen in Drosophila Cells for Kinases Involved in TOR Regulation
    TRAM ANH THI TRAN; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The tuberous sclerosis complex genes (TSC1) and 2-(TSC2) encode proteins that form a complex with tumor suppressor function...
  50. Ernesto Bernal-Mizrachi; Fiscal Year: 2015
    ..During the current funding period, we focused on the mechanisms by which Akt and the tuberous sclerosis complex 2 (TSC2) regulate [unreadable]-cell mass and cell cycle progression...
  51. Epileptogenesis in a rat model of tuberous sclerosis
    Adriana Emmi; Fiscal Year: 2003
    ..While insights into TS have been greatly advanced by our understanding of the underlying genes (TSC1 and TSC2), the connections between TS gene mutations and brain hamartomas (and particularly cortical tubers), and between ..
  52. Regulation of Cellular Survival, Size and Metabolism
    DAVID PLAS; Fiscal Year: 2007
    ..The effects of the expression of hamartin and tuberin on these same processes will be assessed, as well as the possibility that TSC2 is an Akt substrate...
  53. MUTANT ANALYSIS OF TSC1 & TSC2 IN TSC RELATED DISORDERS
    Sandra Dabora; Fiscal Year: 2003
    ..Two disease genes, TSC1 and TSC2 have been identified recently...
  54. MUTANT ANALYSIS OF TSC1 & TSC2 IN TSC RELATED DISORDERS
    Sandra Dabora; Fiscal Year: 2000
    ..Two disease genes, TSC1 and TSC2 have been identified recently...
  55. VEGF regulation by the TSC2 tumor suppressor
    James Brugarolas; Fiscal Year: 2009
    Loss of function mutations in the Tuberous Sclerosis Complex 2 gene (TSC2) result in Tuberous Sclerosis Complex (TSC), a disease characterized by the development of tumors in many tissues...
  56. The role of FOXO transcriptional factors in TSC-mediated tumorigenesis
    Ronald DePinho; Fiscal Year: 2009
    Tuberous Sclerosis (TSC) is caused by mutation in either TSC1 or TSC2 gene and is characterized by the formation of hamartomas in a variety of organs. However, the development of malignancy is very rare in TSC...
  57. Pathogenesis of Lymphangioleiomyomatosis
    Lucia Schuger; Fiscal Year: 2010
    ..lymphangioleiomyomatosis (LAM) is a poorly understood disorder characterized by abnormal smooth muscle (SM)-like, tuberin-minus cell proliferation leading to lung destruction and pseudocyst formation...
  58. BioLINCC
    Carol Giffen; Fiscal Year: 2009
    ..Retrovirus Epidemiology Donor Study (REDS) program, the Honolulu Heart Program (HHP), the Lymphangioleiomyomatosis (LAM) Registry, the Thrombolysis in Myocar-dial Infarction (TIMI) studies and the Cooperative Study of Sickle Cell ..
  59. BioLINCC
    Carol Giffen; Fiscal Year: 2010
    ..Retrovirus Epidemiology Donor Study (REDS) program, the Honolulu Heart Program (HHP), the Lymphangioleiomyomatosis (LAM) Registry, the Thrombolysis in Myocar-dial Infarction (TIMI) studies and the Cooperative Study of Sickle Cell ..
  60. Elizabeth P Henske; Fiscal Year: 2016
    ..LAM is caused by inactivating mutations in the TSC2 gene, resulting in hyperactivation of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and inhibition of ..
  61. Jane Yu; Fiscal Year: 2014
    ..Our central hypothesis is that estrogen promotes the survival of tuberin-deficient cells, thereby allowing LAM cells to accumulate in the lungs and lymphatics...
  62. The Role of TSC2 in EMT: A Model for LAM
    Raymond Yeung; Fiscal Year: 2010
    ..In this proposal, we will examine the role of the TSC2 gene and sex hormones in a novel 'two-hit'model of LAM development that may provide new strategies ..
  63. PHASE III TRIAL FO SIROLIMUS IN LYMPHANGIOLEIOMYLMATOSIS
    Francis McCormack; Fiscal Year: 2009
    ..Functional deficiencies of the encoded products, tuberin or hamartin, result in dysregulated signaling through the Akt pathway which controls cell growth, movement and ..
  64. Utility of Rapamycin for the Treatment of Renal Angiomy*
    John Bissler; Fiscal Year: 2004
    ..kidney, caused by well-characterized inactivating mutations at genetic loci that encode the interacting proteins, tuberin or hamartin...
  65. The 2007 LAM Foundation Lymphangioleiomyomatosis International Research Conferenc
    Francis McCormack; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] The LAM Foundation 2007 Lymphangioleiomyomatosis International Research Conference will focus on the molecular mechanisms of genetic mutation, metastasis and ..
  66. Lymphangioleiomyomatosis Research Conference 2006
    Francis McCormack; Fiscal Year: 2006
    unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] The LAM Foundation 2006 Lymphangioleiomyomatosis International Research Conference will focus on the molecular mechanisms of smooth muscle proliferation and ..
  67. Analysis of the Human c-myc Gene Replication Origin
    Michael Leffak; Fiscal Year: 2012
    ..In Aim 3, a naturally occurring asymmetric polypurine7polypyrimidine sequence derived from the human PKD1/TSC2 locus, which we have shown to form a natural stalled replication fork, will be replicated from the ectopic c-myc ..
  68. Mouse Model of Pancreatic Tumorigenesis with Dysregulation of mTOR
    Chongjuan Wei; Fiscal Year: 2009
    ..of mTOR [mammalian target of rapamycin] signaling via AMPK activation of the tuberous sclerosis complex 2 (TSC2)...
  69. Skin Manifestations of Tuberous Sclerosis
    Jack Arbiser; Fiscal Year: 2009
    ..The first one cloned is tsd (hamartin), localized to chromosome 9, and the second one is tsc2 (tuberin), localized to chromosome 16...
  70. Role of p70 S6 Kinase in Regulating LAM Cell Growth
    Vera P Krymskaya; Fiscal Year: 2010
    ..LAM is associated with mutational inactivation of the tumor suppressors tuberous sclerosis complex 1 (TSC1) and TSC2;loss of TSC2, in particular, is correlated with disease severity and tumor growth...