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
Products:     TSC2

Top Publications

  1. Hodges A, Li S, Maynard J, Parry L, Braverman R, Cheadle J, et al. Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Hum Mol Genet. 2001;10:2899-905 pubmed
    Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely to be closely linked...
  2. Pan C, Chung M, Ng K, Liu C, Wang J, Chai C, et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol. 2008;214:387-93 pubmed
    ..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...
  3. Huang J, Dibble C, Matsuzaki M, Manning B. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol. 2008;28:4104-15 pubmed publisher
    ..mTOR complex 1 (mTORC1) phosphorylates S6K1, while mTORC2 phosphorylates Akt. The TSC1-TSC2 complex is a critical negative regulator of mTORC1...
  4. van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, et al. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. 1998;7:1053-7 pubmed
    ..TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and rab5...
  5. Lesma E, Sirchia S, Ancona S, Carelli S, Bosari S, Ghelma F, et al. The methylation of the TSC2 promoter underlies the abnormal growth of TSC2 angiomyolipoma-derived smooth muscle cells. Am J Pathol. 2009;174:2150-9 pubmed publisher
    ..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...
  6. Carsillo T, Astrinidis A, Henske E. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000;97:6085-90 pubmed
    ..We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC ..
  7. Li Y, Inoki K, Guan K. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol. 2004;24:7965-75 pubmed
    Tuberous sclerosis complex (TSC) is a genetic disease caused by a mutation in either the tsc1 or tsc2 tumor suppressor gene...
  8. Chan J, Zhang H, Roberts P, Jozwiak S, Wieslawa G, Lewin Kowalik J, et al. Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol. 2004;63:1236-42 pubmed
    ..of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex...
  9. Benvenuto G, Li S, Brown S, Braverman R, Vass W, Cheadle J, et al. The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination. Oncogene. 2000;19:6306-16 pubmed
    ..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 ..
  10. Dabora S, Jozwiak S, Franz D, Roberts P, Nieto A, Chung J, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. 2001;68:64-80 pubmed
    ..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 ..

Detail Information

Publications67

  1. Hodges A, Li S, Maynard J, Parry L, Braverman R, Cheadle J, et al. Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Hum Mol Genet. 2001;10:2899-905 pubmed
    Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely to be closely linked...
  2. Pan C, Chung M, Ng K, Liu C, Wang J, Chai C, et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol. 2008;214:387-93 pubmed
    ..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...
  3. Huang J, Dibble C, Matsuzaki M, Manning B. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol. 2008;28:4104-15 pubmed publisher
    ..mTOR complex 1 (mTORC1) phosphorylates S6K1, while mTORC2 phosphorylates Akt. The TSC1-TSC2 complex is a critical negative regulator of mTORC1...
  4. van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, et al. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. 1998;7:1053-7 pubmed
    ..TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and rab5...
  5. Lesma E, Sirchia S, Ancona S, Carelli S, Bosari S, Ghelma F, et al. The methylation of the TSC2 promoter underlies the abnormal growth of TSC2 angiomyolipoma-derived smooth muscle cells. Am J Pathol. 2009;174:2150-9 pubmed publisher
    ..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...
  6. Carsillo T, Astrinidis A, Henske E. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000;97:6085-90 pubmed
    ..We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC ..
  7. Li Y, Inoki K, Guan K. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol. 2004;24:7965-75 pubmed
    Tuberous sclerosis complex (TSC) is a genetic disease caused by a mutation in either the tsc1 or tsc2 tumor suppressor gene...
  8. Chan J, Zhang H, Roberts P, Jozwiak S, Wieslawa G, Lewin Kowalik J, et al. Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol. 2004;63:1236-42 pubmed
    ..of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex...
  9. Benvenuto G, Li S, Brown S, Braverman R, Vass W, Cheadle J, et al. The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination. Oncogene. 2000;19:6306-16 pubmed
    ..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 ..
  10. Dabora S, Jozwiak S, Franz D, Roberts P, Nieto A, Chung J, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. 2001;68:64-80 pubmed
    ..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 ..
  11. El Hashemite N, Zhang H, Henske E, Kwiatkowski D. Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma. Lancet. 2003;361:1348-9 pubmed
    ..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 ..
  12. Rosner M, Freilinger A, Lubec G, Hengstschlager M. The tuberous sclerosis genes, TSC1 and TSC2, trigger different gene expression responses. Int J Oncol. 2005;27:1411-24 pubmed
    ..The genes, TSC1 on chromosome 9q34, encoding hamartin, and TSC2 on chromosome 16p13.3, encoding tuberin are responsible for TSC...
  13. Kataoka K, Fujimoto K, Ito D, Koizumi M, Toyoda E, Mori T, et al. Expression and prognostic value of tuberous sclerosis complex 2 gene product tuberin in human pancreatic cancer. Surgery. 2005;138:450-5 pubmed
    ..disorder caused by mutation of either of 2 tumor suppressor genes, TSC1 or TSC2, which encode hamartin and tuberin, respectively...
  14. Astrinidis A, Senapedis W, Henske E. Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner. Hum Mol Genet. 2006;15:287-97 pubmed
    ..Hamartin and tuberin, the products of TSC1 and TSC2, respectively, form heterodimers and inhibit the mammalian target of rapamycin...
  15. Sancak O, Nellist M, Goedbloed M, Elfferich P, Wouters C, Maat Kievit A, et al. 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. Eur J Hum Genet. 2005;13:731-41 pubmed
    ..TSC is caused by mutations in either the TSC1 or TSC2 gene...
  16. Astrinidis A, Senapedis W, Coleman T, Henske E. Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B. J Biol Chem. 2003;278:51372-9 pubmed
    ..Hamartin and tuberin, the products of the TSC1 and TSC2 genes, respectively, form a complex and inhibit signaling by the mammalian ..
  17. Finlay G, York B, Karas R, Fanburg B, Zhang H, Kwiatkowski D, et al. 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. J Biol Chem. 2004;279:23114-22 pubmed
    ..We hypothesized that tuberin, the protein product of TSC2, binds to estrogen receptors (ER) and regulates the growth effect of E2...
  18. Inoki K, Li Y, Xu T, Guan K. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003;17:1829-34 pubmed
    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...
  19. Roux P, Ballif B, Anjum R, Gygi S, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci U S A. 2004;101:13489-94 pubmed
    ..disorder caused by mutations in either of the two tumor suppressor genes TSC1 or TSC2, which encode hamartin and tuberin, respectively...
  20. Habib S, Riley D, Mahimainathan L, Bhandari B, Choudhury G, Abboud H. Tuberin regulates the DNA repair enzyme OGG1. Am J Physiol Renal Physiol. 2008;294:F281-90 pubmed
    ..The TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas...
  21. Knowles M, Hornigold N, Pitt E. Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours. Biochem Soc Trans. 2003;31:597-602 pubmed
    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...
  22. Lee D, Kuo H, Chen C, Hsu J, Chou C, Wei Y, et al. IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell. 2007;130:440-55 pubmed
    ..The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function ..
  23. Goncharova E, Goncharov D, Spaits M, Noonan D, Talovskaya E, Eszterhas A, et al. Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for tumor suppressor TSC2. Am J Respir Cell Mol Biol. 2006;34:561-72 pubmed
    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...
  24. Jones A, Daniells C, Snell R, Tachataki M, Idziaszczyk S, Krawczak M, et al. Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis. Hum Mol Genet. 1997;6:2155-61 pubmed
    ..TSC exhibits locus heterogeneity: the TSC2 gene is located at 16p13...
  25. Orlova K, Crino P. The tuberous sclerosis complex. Ann N Y Acad Sci. 2010;1184:87-105 pubmed publisher
    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...
  26. Garami A, Zwartkruis F, Nobukuni T, Joaquin M, Roccio M, Stocker H, et al. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell. 2003;11:1457-66 pubmed
    ..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. Lesma E, Grande V, Ancona S, Carelli S, Di Giulio A, Gorio A. Anti-EGFR antibody efficiently and specifically inhibits human TSC2-/- smooth muscle cell proliferation. Possible treatment options for TSC and LAM. PLoS ONE. 2008;3:e3558 pubmed publisher
    ..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...
  28. Neuman N, Henske E. Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis. EMBO Mol Med. 2011;3:189-200 pubmed publisher
    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)...
  29. Plank T, Yeung R, Henske E. Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Cancer Res. 1998;58:4766-70 pubmed
    ..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 ..
  30. Jones A, Shyamsundar M, Thomas M, Maynard J, Idziaszczyk S, Tomkins S, et al. Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. Am J Hum Genet. 1999;64:1305-15 pubmed
    ..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 ..
  31. York B, Lou D, Noonan D. Tuberin nuclear localization can be regulated by phosphorylation of its carboxyl terminus. Mol Cancer Res. 2006;4:885-97 pubmed
    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...
  32. Au K, Williams A, Roach E, Batchelor L, Sparagana S, Delgado M, et al. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. 2007;9:88-100 pubmed
    ..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...
  33. Carelli S, Lesma E, Paratore S, Grande V, Zadra G, Bosari S, et al. Survivin expression in tuberous sclerosis complex cells. Mol Med. 2007;13:166-77 pubmed
    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...
  34. Inoki K, Li Y, Zhu T, Wu J, Guan K. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002;4:648-57 pubmed
    ..Mutation in either the TSC1 or TSC2 tumour suppressor gene is responsible for both the familial and sporadic forms of this disease...
  35. Tee A, Fingar D, Manning B, Kwiatkowski D, Cantley L, Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A. 2002;99:13571-6 pubmed
    ..that occurs upon mutation of either the TSC1 or TSC2 genes, which encode the protein products hamartin and tuberin, respectively...
  36. Li Y, Inoki K, Yeung R, Guan K. Regulation of TSC2 by 14-3-3 binding. J Biol Chem. 2002;277:44593-6 pubmed
    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...
  37. Karbowniczek M, Cash T, Cheung M, Robertson G, Astrinidis A, Henske E. Regulation of B-Raf kinase activity by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent. J Biol Chem. 2004;279:29930-7 pubmed
    ..The products of the TSC1 and TSC2 genes, hamartin and tuberin, respectively, heterodimerize and inhibit the mammalian target of rapamycin (mTOR)...
  38. Liu M, Cai S, Espejo A, Bedford M, Walker C. 14-3-3 interacts with the tumor suppressor tuberin at Akt phosphorylation site(s). Cancer Res. 2002;62:6475-80 pubmed
    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...
  39. Han S, Santos T, Puga A, Roy J, Thiele E, McCollin M, et al. Phosphorylation of tuberin as a novel mechanism for somatic inactivation of the tuberous sclerosis complex proteins in brain lesions. Cancer Res. 2004;64:812-6 pubmed
    ..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 ..
  40. Zhang H, Cicchetti G, Onda H, Koon H, Asrican K, Bajraszewski N, et al. Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J Clin Invest. 2003;112:1223-33 pubmed
    Tuberous sclerosis (TSC) is a familial tumor syndrome due to mutations in TSC1 or TSC2, in which progression to malignancy is rare...
  41. Li Y, Inoki K, Vacratsis P, Guan K. The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 gene product, and enhances its interaction with 14-3-3. J Biol Chem. 2003;278:13663-71 pubmed
    ..TSC1 and TSC2 (also known as hamartin and tuberin, respectively) form a functional complex and negatively regulate cell growth by inhibiting protein synthesis...
  42. Au K, Ward C, Northrup H. Tuberous sclerosis complex: disease modifiers and treatments. Curr Opin Pediatr. 2008;20:628-33 pubmed publisher
    ..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...
  43. Lee P, Tsang S, Moses M, Trayes Gibson Z, Hsiao L, Jensen R, et al. Rapamycin-insensitive up-regulation of MMP2 and other genes in tuberous sclerosis complex 2-deficient lymphangioleiomyomatosis-like cells. Am J Respir Cell Mol Biol. 2010;42:227-34 pubmed publisher
    ..The objective of this study was to investigate how tuberous sclerosis complex (TSC) 1 or TSC2 deficiency alters MMP expression and regulation...
  44. Dibble C, Elis W, Menon S, Qin W, Klekota J, Asara J, et al. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell. 2012;47:535-46 pubmed publisher
    The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex, which limits cell growth in response to poor growth conditions...
  45. Ozcan U, Ozcan L, Yilmaz E, Düvel K, Sahin M, Manning B, et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell. 2008;29:541-51 pubmed publisher
    ..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,..
  46. . Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993;75:1305-15 pubmed
    ..The 5.5 kb TSC2 transcript is widely expressed, and its protein product, tuberin, has a region of homology to the GTPase-activating protein GAP3.
  47. Lesma E, Grande V, Carelli S, Brancaccio D, Canevini M, Alfano R, et al. 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. Am J Pathol. 2005;167:1093-103 pubmed
    Tuberous sclerosis complex (TSC) is a tumor suppressor gene disorder characterized by mutations in the TSC1 or TSC2 genes...
  48. Niida Y, Lawrence Smith N, Banwell A, Hammer E, Lewis J, Beauchamp R, et al. Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis. Hum Mutat. 1999;14:412-22 pubmed
    ..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...
  49. Nellist M, van Slegtenhorst M, Goedbloed M, van den Ouweland A, Halley D, van der Sluijs P. Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin. J Biol Chem. 1999;274:35647-52 pubmed
    ..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...
  50. Lou D, Griffith N, Noonan D. The tuberous sclerosis 2 gene product can localize to nuclei in a phosphorylation-dependent manner. Mol Cell Biol Res Commun. 2001;4:374-80 pubmed
    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...
  51. York B, Lou D, Panettieri R, Krymskaya V, Vanaman T, Noonan D. Cross-talk between tuberin, calmodulin, and estrogen signaling pathways. FASEB J. 2005;19:1202-4 pubmed
    ..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 ..
  52. Nellist M, Verhaaf B, Goedbloed M, Reuser A, van den Ouweland A, Halley D. TSC2 missense mutations inhibit tuberin phosphorylation and prevent formation of the tuberin-hamartin complex. Hum Mol Genet. 2001;10:2889-98 pubmed
    ..TSC1 and TSC2 encode two large novel proteins called hamartin and tuberin, respectively...
  53. Manning B, Tee A, Logsdon M, Blenis J, Cantley L. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell. 2002;10:151-62 pubmed
    ..This approach identifies the tuberous sclerosis complex-2 gene product, tuberin, as a potential target of Akt/PKB...
  54. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004;18:1926-45 pubmed
    ..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. ..
  55. Wienecke R, Konig A, DeClue J. Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity. J Biol Chem. 1995;270:16409-14 pubmed
    ..The putative TSC2 product (tuberin) contains a region of limited homology to the catalytic domain of Rap1GAP...
  56. Cai S, Tee A, Short J, Bergeron J, Kim J, Shen J, et al. Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning. J Cell Biol. 2006;173:279-89 pubmed
    Loss of tuberin, the product of TSC2 gene, increases mammalian target of rapamycin (mTOR) signaling, promoting cell growth and tumor development...
  57. Chakraborty S, Mohiyuddin S, Gopinath K, Kumar A. Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma. BMC Cancer. 2008;8:163 pubmed publisher
    ..We therefore investigated the role of the tumor suppressor genes, TSC1 and TSC2, and other members of this pathway in tumorigenesis of OSCC...
  58. Mak B, Takemaru K, Kenerson H, Moon R, Yeung R. The tuberin-hamartin complex negatively regulates beta-catenin signaling activity. J Biol Chem. 2003;278:5947-51 pubmed
    ..Their protein products, hamartin and tuberin, respectively, form a functional complex that affects cell growth, differentiation, and proliferation...
  59. Castro A, Rebhun J, Clark G, Quilliam L. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem. 2003;278:32493-6 pubmed
    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...
  60. Ballif B, Roux P, Gerber S, Mackeigan J, Blenis J, Gygi S. Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors. Proc Natl Acad Sci U S A. 2005;102:667-72 pubmed
    ..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 ..
  61. Ma L, Chen Z, Erdjument Bromage H, Tempst P, Pandolfi P. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell. 2005;121:179-93 pubmed
    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)...
  62. Rosner M, Freilinger A, Hanneder M, Fujita N, Lubec G, Tsuruo T, et al. p27Kip1 localization depends on the tumor suppressor protein tuberin. Hum Mol Genet. 2007;16:1541-56 pubmed
    ..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...
  63. Rok P, Kasprzyk Obara J, Domańska Pakieła D, Jozwiak S. Clinical symptoms of tuberous sclerosis complex in patients with an identical TSC2 mutation. Med Sci Monit. 2005;11:CR230-234 pubmed
    ..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...
  64. Kozlowski P, Roberts P, Dabora S, Franz D, Bissler J, Northrup H, et al. Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Hum Genet. 2007;121:389-400 pubmed
    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...
  65. Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006;126:955-68 pubmed
    Mutation in the TSC2 tumor suppressor causes tuberous sclerosis complex, a disease characterized by hamartoma formation in multiple tissues...
  66. Clements D, Mayer R, Johnson S. 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. Am J Physiol Lung Cell Mol Physiol. 2007;292:L258-66 pubmed
    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...