Tsc1

Summary

Gene Symbol: Tsc1
Description: tuberous sclerosis 1
Alias: hamartin, tuberous sclerosis 1 protein homolog
Species: mouse
Products:     Tsc1

Top Publications

  1. Chen C, Liu Y, Liu R, Ikenoue T, Guan K, Liu Y, et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med. 2008;205:2397-408 pubmed publisher
    ..We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs)...
  2. Patursky Polischuk I, Stolovich Rain M, Hausner Hanochi M, Kasir J, Cybulski N, Avruch J, et al. The TSC-mTOR pathway mediates translational activation of TOP mRNAs by insulin largely in a raptor- or rictor-independent manner. Mol Cell Biol. 2009;29:640-9 pubmed publisher
    ..This translational activation involves the tuberous sclerosis complex (TSC), as the knockout of TSC1 or TSC2 rescues TOP mRNAs from translational repression in mitotically arrested cells...
  3. Gan B, Sahin E, Jiang S, Sanchez Aguilera A, Scott K, Chin L, et al. mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. Proc Natl Acad Sci U S A. 2008;105:19384-9 pubmed publisher
    The Tuberous Sclerosis Complex component, TSC1, functions as a tumor suppressor via its regulation of diverse cellular processes, particularly cell growth...
  4. Cornu M, Oppliger W, Albert V, Robitaille A, Trapani F, Quagliata L, et al. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21. Proc Natl Acad Sci U S A. 2014;111:11592-9 pubmed publisher
    ..of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1)...
  5. Yecies J, Zhang H, Menon S, Liu S, Yecies D, Lipovsky A, et al. Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Cell Metab. 2011;14:21-32 pubmed publisher
    ..the role of mTORC1 in the regulation of SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1 (LTsc1KO), which results in insulin-independent activation of mTORC1...
  6. 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...
  7. Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008;28:5422-32 pubmed publisher
    Tuberous sclerosis (TSC) is a hamartoma syndrome attributable to mutations in either TSC1 or TSC2 in which brain involvement causes epilepsy, mental retardation, and autism. We have reported recently (Meikle et al...
  8. Miloslavski R, Cohen E, Avraham A, Iluz Y, Hayouka Z, Kasir J, et al. Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner. J Mol Cell Biol. 2014;6:255-66 pubmed publisher
    ..This mode of regulation involves TSC and Rheb, as knockout of TSC1 or TSC2 or overexpression of Rheb rescued TOP mRNA translation in oxygen-deprived cells...
  9. Meikle L, Talos D, Onda H, Pollizzi K, Rotenberg A, Sahin M, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci. 2007;27:5546-58 pubmed
    Tuberous sclerosis (TSC) is a hamartoma syndrome caused by mutations in TSC1 or TSC2 in which cerebral cortical tubers and seizures are major clinical issues...

More Information

Publications66

  1. Knight Z, Tan K, Birsoy K, Schmidt S, Garrison J, Wysocki R, et al. Molecular profiling of activated neurons by phosphorylated ribosome capture. Cell. 2012;151:1126-37 pubmed publisher
    ..These studies identify elements of the neural circuit that controls food intake and illustrate how the activity-dependent capture of cell-type-specific transcripts can elucidate the functional organization of a complex tissue. ..
  2. Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, Kwiatkowski D, et al. Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Nat Med. 2008;14:843-8 pubmed publisher
    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...
  3. Zeng L, Rensing N, Zhang B, Gutmann D, Gambello M, Wong M. Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex. Hum Mol Genet. 2011;20:445-54 pubmed publisher
    ..Two genes, TSC1 and TSC2, encoding the proteins hamartin and tuberin, respectively, have been identified as causing TSC...
  4. Goorden S, van Woerden G, van der Weerd L, Cheadle J, Elgersma Y. Cognitive deficits in Tsc1+/- mice in the absence of cerebral lesions and seizures. Ann Neurol. 2007;62:648-55 pubmed
    ..Here, we reinvestigated the relation among cerebral lesions, epilepsy, and cognitive function using Tsc1+/- mice...
  5. Erbayat Altay E, Zeng L, Xu L, Gutmann D, Wong M. The natural history and treatment of epilepsy in a murine model of tuberous sclerosis. Epilepsia. 2007;48:1470-6 pubmed
    ..We previously described a novel model of TSC, due to conditional inactivation of the Tsc1 gene in glia (Tsc1(GFAP)CKO mice), in which mice develop epilepsy and premature death...
  6. Sathaliyawala T, O Gorman W, Greter M, Bogunovic M, Konjufca V, Hou Z, et al. Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. Immunity. 2010;33:597-606 pubmed publisher
    ..Thus, PI3K-mTOR signaling downstream of Flt3L controls DC development, and its restriction by Pten ensures optimal DC pool size and subset composition. ..
  7. Sato A, Kasai S, Kobayashi T, Takamatsu Y, Hino O, Ikeda K, et al. Rapamycin reverses impaired social interaction in mouse models of tuberous sclerosis complex. Nat Commun. 2012;3:1292 pubmed publisher
    ..accompany autism spectrum disorder, such as tuberous sclerosis complex caused by haploinsufficiency of the TSC1 and TSC2 genes...
  8. Sengupta S, Peterson T, Laplante M, Oh S, Sabatini D. mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature. 2010;468:1100-4 pubmed publisher
    ..Here we show that mTORC1 controls ketogenesis in mice in response to fasting. We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a ..
  9. O Brien T, Gorentla B, Xie D, Srivatsan S, McLeod I, He Y, et al. Regulation of T-cell survival and mitochondrial homeostasis by TSC1. Eur J Immunol. 2011;41:3361-70 pubmed publisher
    ..However, the importance of mTOR regulation in T cells has yet to be explored. The TSC1/TSC2 complex has been shown to inhibit mTORC1 signaling in cell line models...
  10. Carson R, Van Nielen D, Winzenburger P, Ess K. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiol Dis. 2012;45:369-80 pubmed publisher
    ..Here we address abnormal brain development in TSC by inactivating the mouse Tsc1 gene in embryonic neural progenitor cells...
  11. Zeng L, Xu L, Gutmann D, Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol. 2008;63:444-53 pubmed publisher
    ..Mice with conditional inactivation of the Tsc1 gene primarily in glia (Tsc1(GFAP)CKO mice) develop glial proliferation, progressive epilepsy, and premature death...
  12. Kobayashi T, Minowa O, Sugitani Y, Takai S, Mitani H, Kobayashi E, et al. A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice. Proc Natl Acad Sci U S A. 2001;98:8762-7 pubmed
    ..is characterized by the development of hamartomas in various organs and is caused by a germ-line mutation in either TSC1 or TSC2 tumor suppressor genes...
  13. Bilanges B, Argonza Barrett R, Kolesnichenko M, Skinner C, Nair M, Chen M, et al. Tuberous sclerosis complex proteins 1 and 2 control serum-dependent translation in a TOP-dependent and -independent manner. Mol Cell Biol. 2007;27:5746-64 pubmed
    The tuberous sclerosis complex (TSC) proteins TSC1 and TSC2 regulate protein translation by inhibiting the serine/threonine kinase mTORC1 (for mammalian target of rapamycin complex 1)...
  14. Bateup H, Takasaki K, Saulnier J, Denefrio C, Sabatini B. Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. J Neurosci. 2011;31:8862-9 pubmed publisher
    The autism spectrum disorder tuberous sclerosis complex (TSC) is caused by mutations in the Tsc1 or Tsc2 genes, whose protein products form a heterodimeric complex that negatively regulates mammalian target of rapamycin-dependent protein ..
  15. Yang K, Neale G, Green D, He W, Chi H. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nat Immunol. 2011;12:888-97 pubmed publisher
    The mechanisms that regulate T cell quiescence are poorly understood. We report that the tumor suppressor Tsc1 established a quiescence program in naive T cells by controlling cell size, cell cycle entry and responses to stimulation of ..
  16. Zhou J, Brugarolas J, Parada L. Loss of Tsc1, but not Pten, in renal tubular cells causes polycystic kidney disease by activating mTORC1. Hum Mol Genet. 2009;18:4428-41 pubmed publisher
    Tuberous sclerosis complex (TSC) is a genetic disorder linked to mutations of either the TSC1 or TSC2 gene, which encode proteins that form a complex to negatively regulate mammalian target of rapamycin complex 1 (mTORC1)...
  17. Kwiatkowski D, Zhang H, Bandura J, Heiberger K, Glogauer M, El Hashemite N, et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet. 2002;11:525-34 pubmed
    ..with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin. Hyperphosphorylation of S6 is also seen in kidney tumors in the heterozygote mice, suggesting that inhibition of ..
  18. Pan H, O Brien T, Wright G, Yang J, Shin J, Wright K, et al. Critical role of the tumor suppressor tuberous sclerosis complex 1 in dendritic cell activation of CD4 T cells by promoting MHC class II expression via IRF4 and CIITA. J Immunol. 2013;191:699-707 pubmed publisher
    ..We report in this article that the tumor suppressor tuberous sclerosis complex 1 (TSC1) is a critical regulator of DC function for both innate and adaptive immunity...
  19. Tsai P, Hull C, Chu Y, Greene Colozzi E, Sadowski A, Leech J, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012;488:647-51 pubmed publisher
    ..sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling...
  20. Liang M, Ma J, Chen L, Kozlowski P, Qin W, Li D, et al. TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity. Oncogene. 2010;29:1588-97 pubmed publisher
    Germline TSC1 or TSC2 mutations cause tuberous sclerosis complex (TSC), a hamartoma syndrome with lung involvement...
  21. Feliciano D, Quon J, Su T, Taylor M, Bordey A. Postnatal neurogenesis generates heterotopias, olfactory micronodules and cortical infiltration following single-cell Tsc1 deletion. Hum Mol Genet. 2012;21:799-810 pubmed publisher
    ..associated brain lesions are thought to arise from abnormal embryonic neurogenesis due to inherited mutations in Tsc1 or Tsc2...
  22. Castets P, Lin S, Rion N, Di Fulvio S, Romanino K, Guridi M, et al. Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy. Cell Metab. 2013;17:731-44 pubmed publisher
    ..We show that TSC1-deficient mice (TSCmKO), characterized by sustained activation of mTORC1, develop a late-onset myopathy related to ..
  23. Banerjee S, Crouse N, Emnett R, Gianino S, Gutmann D. Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner. Proc Natl Acad Sci U S A. 2011;108:15996-6001 pubmed publisher
    ..First, we show that Nf1 or Pten inactivation, but not Tsc1 loss or Rheb overexpression, increases astrocyte cell growth in vitro...
  24. Goto J, Talos D, Klein P, Qin W, Chekaluk Y, Anderl S, et al. Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex. Proc Natl Acad Sci U S A. 2011;108:E1070-9 pubmed publisher
    ..Here, we report that mosaic induction of Tsc1 loss in neural progenitor cells in Tsc1(cc) Nestin-rtTA(+) TetOp-cre(+) embryos by doxycycline leads to multiple ..
  25. Robitaille A, Christen S, Shimobayashi M, Cornu M, Fava L, Moes S, et al. Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis. Science. 2013;339:1320-3 pubmed publisher
    ..Thus, mTORC1 also stimulates the synthesis of nucleotides to control cell proliferation. ..
  26. Adhikari D, Zheng W, Shen Y, Gorre N, Hamalainen T, Cooney A, et al. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet. 2010;19:397-410 pubmed publisher
    ..Here we provide genetic evidence to show that the tumor suppressor tuberous sclerosis complex 1 (Tsc1), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the ..
  27. Zhou J, Blundell J, Ogawa S, Kwon C, Zhang W, Sinton C, et al. Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. J Neurosci. 2009;29:1773-83 pubmed publisher
  28. Uhlmann E, Wong M, Baldwin R, Bajenaru M, Onda H, Kwiatkowski D, et al. Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann Neurol. 2002;52:285-96 pubmed
    ..central nervous system abnormalities in mice, we generated two independent lines of astrocyte-specific Tsc1 conditional knockout mice by using the Cre-LoxP system...
  29. Zhou J, Shrikhande G, Xu J, McKay R, Burns D, Johnson J, et al. Tsc1 mutant neural stem/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle. Genes Dev. 2011;25:1595-600 pubmed publisher
    ..However, this hypothesis has not been tested empirically. Here, we report that loss of Tsc1 in mouse subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) results in formation of SEN- and SEGA-like ..
  30. Choi Y, Di Nardo A, Kramvis I, Meikle L, Kwiatkowski D, Sahin M, et al. Tuberous sclerosis complex proteins control axon formation. Genes Dev. 2008;22:2485-95 pubmed publisher
    Axon formation is fundamental for brain development and function. TSC1 and TSC2 are two genes, mutations in which cause tuberous sclerosis complex (TSC), a disease characterized by tumor predisposition and neurological abnormalities ..
  31. Feliciano D, Su T, Lopez J, Platel J, Bordey A. Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice. J Clin Invest. 2011;121:1596-607 pubmed publisher
    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by mutations in Tsc1 or Tsc2 that lead to mammalian target of rapamycin (mTOR) hyperactivity...
  32. Tanaka Y, Park J, Tanwar P, Kaneko Tarui T, Mittal S, Lee H, et al. Deletion of tuberous sclerosis 1 in somatic cells of the murine reproductive tract causes female infertility. Endocrinology. 2012;153:404-16 pubmed publisher
    ..kinase activity of which is kept in an inactive state by a tumor suppressor dimer containing tuberous sclerosis 1 (TSC1) and TSC2...
  33. 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...
  34. Meikle L, McMullen J, Sherwood M, Lader A, Walker V, Chan J, et al. A mouse model of cardiac rhabdomyoma generated by loss of Tsc1 in ventricular myocytes. Hum Mol Genet. 2005;14:429-35 pubmed
    Tuberous sclerosis is a hamartoma syndrome due to mutations in TSC1 or TSC2 in which cardiac rhabdomyomas are seen in approximately 60% of patients...
  35. Wu Q, Liu Y, Chen C, Ikenoue T, Qiao Y, Li C, et al. The tuberous sclerosis complex-mammalian target of rapamycin pathway maintains the quiescence and survival of naive T cells. J Immunol. 2011;187:1106-12 pubmed publisher
    ..In this study, we report that T cell-specific deletion of Tsc1, a negative regulator of mammalian target of rapamycin, resulted in both spontaneous losses of quiescence and ..
  36. Malhowski A, Hira H, Bashiruddin S, Warburton R, Goto J, Robert B, et al. Smooth muscle protein-22-mediated deletion of Tsc1 results in cardiac hypertrophy that is mTORC1-mediated and reversed by rapamycin. Hum Mol Genet. 2011;20:1290-305 pubmed publisher
    ..size and growth, is observed with inactivating mutations of either of the tuberous sclerosis complex (TSC) genes, Tsc1 and Tsc2. Tsc1 and Tsc2 are highly expressed in cardiovascular tissue but their functional role there is unknown...
  37. Way S, McKenna J, Mietzsch U, Reith R, Wu H, Gambello M. Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse. Hum Mol Genet. 2009;18:1252-65 pubmed publisher
  38. Di Nardo A, Kramvis I, Cho N, Sadowski A, Meikle L, Kwiatkowski D, et al. Tuberous sclerosis complex activity is required to control neuronal stress responses in an mTOR-dependent manner. J Neurosci. 2009;29:5926-37 pubmed publisher
    Tuberous sclerosis complex (TSC) is a neurogenetic disorder caused by loss-of-function mutations in either the TSC1 or TSC2 genes and frequently results in prominent CNS manifestations, including epilepsy, mental retardation, and autism ..
  39. Kenerson H, Yeh M, Yeung R. Tuberous sclerosis complex-1 deficiency attenuates diet-induced hepatic lipid accumulation. PLoS ONE. 2011;6:e18075 pubmed publisher
    ..Here, we generated mice with hepatocyte-specific deletion of Tsc1 to study the effects of constitutive mTORC1 activation in the liver...
  40. Wilson C, Idziaszczyk S, Parry L, Guy C, Griffiths D, Lazda E, et al. A mouse model of tuberous sclerosis 1 showing background specific early post-natal mortality and metastatic renal cell carcinoma. Hum Mol Genet. 2005;14:1839-50 pubmed
    ..We detected loss of the wild-type Tsc1 allele and elevated levels of p-mTOR and p-S6 in lesions from Tsc1+/- mice. This new murine model of hamartin deficiency exhibits a more severe phenotype than existing models.
  41. Hernandez O, Way S, McKenna J, Gambello M. Generation of a conditional disruption of the Tsc2 gene. Genesis. 2007;45:101-6 pubmed
    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 gene. Patients afflicted with TSC develop tumors in various organ systems, but cerebral pathology is particularly severe...
  42. Tavazoie S, Alvarez V, Ridenour D, Kwiatkowski D, Sabatini B. Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci. 2005;8:1727-34 pubmed
    Mutations in the TSC1 or TSC2 tumor suppressor genes lead to tuberous sclerosis complex (TSC), a dominant hamartomatous disorder that often presents with mental retardation, epilepsy and autism...
  43. Pan H, O Brien T, Zhang P, Zhong X. The role of tuberous sclerosis complex 1 in regulating innate immunity. J Immunol. 2012;188:3658-66 pubmed publisher
    ..The tuberous sclerosis complex 1 (TSC1) is a tumor suppressor that inhibits the mammalian target of rapamycin (mTOR)...
  44. Wilson C, Bonnet C, Guy C, Idziaszczyk S, Colley J, Humphreys V, et al. Tsc1 haploinsufficiency without mammalian target of rapamycin activation is sufficient for renal cyst formation in Tsc1+/- mice. Cancer Res. 2006;66:7934-8 pubmed
    Tuberous sclerosis complex (TSC) is caused by mutations in either the TSC1 or TSC2 gene...
  45. Zhang L, Zhang H, Li L, Xiao Y, Rao E, Miao Z, et al. TSC1/2 signaling complex is essential for peripheral naïve CD8+ T cell survival and homeostasis in mice. PLoS ONE. 2012;7:e30592 pubmed publisher
    The PI3K-Akt-mTOR pathway plays crucial roles in regulating both innate and adaptive immunity. However, the role of TSC1, a critical negative regulator of mTOR, in peripheral T cell homeostasis remains elusive...
  46. Ghosh S, Tergaonkar V, Rothlin C, Correa R, Bottero V, Bist P, et al. Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kappaB activation and cell survival. Cancer Cell. 2006;10:215-26 pubmed
    The TSC1-TSC2 complex has recently been implicated in cell survival responses...
  47. Anderl S, Freeland M, Kwiatkowski D, Goto J. Therapeutic value of prenatal rapamycin treatment in a mouse brain model of tuberous sclerosis complex. Hum Mol Genet. 2011;20:4597-604 pubmed publisher
    ..In this Tsc1(cc) Nes-cre(+) mouse model, recombination and loss of Tsc1 in neural progenitor cells leads to brain enlargement, ..
  48. Gan B, Lim C, Chu G, Hua S, Ding Z, Collins M, et al. FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell. 2010;18:472-84 pubmed publisher
    mTORC1 is a validated therapeutic target for renal cell carcinoma (RCC). Here, analysis of Tsc1-deficient (mTORC1 hyperactivation) mice uncovered a FoxO-dependent negative feedback circuit constraining mTORC1-mediated renal tumorigenesis...
  49. 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...
  50. Lamb R, Roy C, Diefenbach T, Vinters H, Johnson M, Jay D, et al. The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho. Nat Cell Biol. 2000;2:281-7 pubmed
    ..b>Hamartin, the protein encoded by TSC1, contains a coiled-coil domain and is expressed in most adult tissues, although its ..
  51. Bateup H, Johnson C, Denefrio C, Saulnier J, Kornacker K, Sabatini B. Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis. Neuron. 2013;78:510-22 pubmed publisher
    ..In Tsc1 KO neurons, weakened inhibition caused by deregulated mTOR alters the balance of excitatory and inhibitory synaptic ..
  52. 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...
  53. CHEVERE TORRES I, Kaphzan H, Bhattacharya A, Kang A, Maki J, Gambello M, et al. Metabotropic glutamate receptor-dependent long-term depression is impaired due to elevated ERK signaling in the ?RG mouse model of tuberous sclerosis complex. Neurobiol Dis. 2012;45:1101-10 pubmed publisher
    ..These mice express a dominant/negative TSC2 that binds to TSC1, but has a deletion and substitution mutation in its GAP-domain, resulting in inactivation of the complex...
  54. Xu L, Zeng L, Wong M. Impaired astrocytic gap junction coupling and potassium buffering in a mouse model of tuberous sclerosis complex. Neurobiol Dis. 2009;34:291-9 pubmed
    ..Here, we report that knock-out mice with Tsc1 gene inactivation in glia (Tsc1(GFAP)CKO mice) exhibit decreased expression of the astrocytic connexin protein, ..
  55. Harrington L, Findlay G, Gray A, Tolkacheva T, Wigfield S, Rebholz H, et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol. 2004;166:213-23 pubmed
    ..The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K ..
  56. Brugarolas J, Lei K, Hurley R, Manning B, Reiling J, Hafen E, et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 2004;18:2893-904 pubmed
    ..Here we show that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the hypoxia-inducible gene REDD1/RTP801...
  57. Zeng L, Ouyang Y, Gazit V, Cirrito J, Jansen L, Ess K, et al. Abnormal glutamate homeostasis and impaired synaptic plasticity and learning in a mouse model of tuberous sclerosis complex. Neurobiol Dis. 2007;28:184-96 pubmed
    Mice with inactivation of the Tuberous sclerosis complex-1 (Tsc1) gene in glia (Tsc1 GFAP CKO mice) have deficient astrocyte glutamate transporters and develop seizures, suggesting that abnormal glutamate homeostasis contributes to ..