Gene interactions and pathways from curated databases and text-mining

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Pathways - manually collected, often from reviews:

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

  • STRING interaction: TSC1 — MTOR (interaction, mapped from grid)
  • STRING interaction: MTOR — TSC1 (interaction, mapped from grid)

Text-mined interactions from Literome

Inoki et al., Nat Cell Biol 2002 (Tuberous Sclerosis) : These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR)
Inoki et al., Genes Dev 2003 : These functions of TSC1/TSC2 are likely mediated by mTOR
Brugarolas et al., Genes Dev 2004 (Anoxia) : Here we show that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the hypoxia-inducible gene REDD1/RTP801
Henske et al., Pediatr Nephrol 2005 (Angiomyolipoma...) : Recently, the TSC1/TSC2 protein complex was shown to inhibit the kinase mTOR ( mammalian target of rapamycin )
Mak et al., Am J Pathol 2005 (Angiomyolipoma...) : Besides the negative regulatory role of the TSC1/TSC2 proteins on mTOR , we have reported an effect on beta-catenin signaling at the level of the degradation complex in vitro
Astrinidis et al., Hum Mol Genet 2006 : Hamartin and tuberin, the products of TSC1 and TSC2, respectively, form heterodimers and inhibit the mammalian target of rapamycin
Jozwiak et al., J Neurooncol 2006 (Brain Neoplasms...) : The importance of these proteins is confirmed by their ubiquitous character and by the fact that TSC1/TSC2 complex is involved in the regulation of the activity of mTOR , a master controller of protein translation
Kaur et al., J Biol Chem 2007 : Interestingly, the induction of expression of ISG15 and CXCL10 proteins by IFNs was also strongly enhanced in cells lacking expression of the tuberin ( TSC2 ( -/- ) ) or hamartin ( TSC1 ( -/- ) ) genes, consistent with the known negative regulatory effect of the TSC1-TSC2 complex on mTOR activation
Pelletier et al., Cancer Res 2007 : Consistent with this finding, genetic ablation of Tsc1 , a major upstream inhibitor of mTOR , resulted in nucleophosmin protein induction through increased translation of existing nucleophosmin mRNAs
Lee et al., EMBO J 2007 (Hamartoma...) : Thus, loss of TSC1 or TSC2, the negative regulators of mTOR , results in dramatic accumulation of p53 and apoptosis in response to stress conditions
Jozwiak et al., Lancet Oncol 2008 (Tuberous Sclerosis) : Tumours in which loss of heterozygosity is rare, such as subependymal giant-cell astrocytoma, might all share a common feature that mimics loss of heterozygosity either by inactivation of the TSC complex or by direct activation of mammalian target of rapamycin (mTOR) or its downstream targets
Moorman et al., Cell Host Microbe 2008 (Cytomegalovirus Infections) : TSC1/2 integrates stress signals and regulates the mammalian target of rapamycin complex 1 ( mTORC1 ), a protein complex that responds to stress by limiting protein synthesis and cell growth
Huang et al., Mol Cell Biol 2008 : The TSC1-TSC2 complex is required for proper activation of mTOR complex 2 ... However, how mTORC2 is regulated and whether the TSC1-TSC2 complex is involved are unknown ... Our data also suggest that the TSC1-TSC2 complex positively regulates mTORC2 in a manner independent of its GTPase activating protein activity toward Rheb ... These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation ... These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2 , which through different mechanisms promotes Akt activation
Lu et al., Clin Cancer Res 2008 (Endometrial Neoplasms...) : Loss of tuberous sclerosis complex-2 function and activation of mammalian target of rapamycin signaling in endometrial carcinoma
Dan et al., J Immunol 2008 : mTOR is negatively controlled by the tuberous sclerosis complex 1/2 (TSC1/2) , and activation of Akt induces phosphorylation of TSC2, which blocks the repressive TSC1/2 activity
Buller et al., Am J Physiol Cell Physiol 2008 : Since GSK-3 can inhibit mammalian target of rapamycin (mTOR) signaling via phosphorylation of the tuberous sclerosis complex subunit 2 ( TSC2 ) tumor suppressor, we investigated whether chronic GSK-3 effects on glucose uptake and GLUT1 expression depended on TSC2 phosphorylation and TSC inhibition of mTOR
Yu et al., Mol Cancer Ther 2008 : Overexpression of constitutively activated Akt or disruption of TSC1-TSC2 complex by small interfering RNA or gene knockout only partially restored curcumin mediated inhibition of mTOR and downstream signaling, indicating that they are not the primary effectors of curcumin mediated inhibition of Akt/mTOR signaling
Coevoets et al., Eur J Hum Genet 2009 (Tuberous Sclerosis) : We have developed a straightforward, semiautomated in-cell western ( ICW ) assay to investigate the effects of amino acid changes on the TSC1-TSC2 dependent inhibition of mTOR activity
Pollizzi et al., Molecular cancer 2009 (Disease Models, Animal...) : Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1 and suppression of AKT
Zhang et al., PloS one 2009 : Loss of function of the TSC1-TSC2 complex results in constitutive mTORC1 signaling and, through mTORC1 dependent feedback mechanisms and loss of mTORC2 activity, leads to a concomitant block of Akt signaling to its other downstream targets
Huang et al., Cancer Res 2009 (Angiomyolipoma...) : We also show that the TSC1-TSC2 complex can directly stimulate the in vitro kinase activity of mTORC2
Matthew et al., Cell cycle (Georgetown, Tex.) 2009 (Disease Models, Animal...) : Tuberous sclerosis complex 1 (TSC1) inhibits mammalian target of rapamycin (mTOR) , a central promotor of cell growth and proliferation
Vega-Rubin-de-Celis et al., Biochemistry 2010 : REDD1 induced-mTORC1 inhibition requires the TSC1/TSC2 complex , and REDD1 has been proposed to act by directly binding to and sequestering 14-3-3 proteins away from TSC2 leading to TSC2 dependent inhibition of mTORC1
Linehan et al., Nat Rev Urol 2010 (Carcinoma, Renal Cell...) : TSC1-TSC2 is downstream of AMPK and negatively regulates mTOR in response to cellular energy deficit
Yoshida et al., Nat Med 2010 (Pulmonary Emphysema) : Rtp801 ( also known as Redd1, and encoded by Ddit4 ), a stress related protein triggered by adverse environmental conditions, inhibits mammalian target of rapamycin (mTOR) by stabilizing the TSC1-TSC2 inhibitory complex and enhances oxidative stress dependent cell death
Kladney et al., Cancer Res 2010 (Prostatic Intraepithelial Neoplasia...) : Here, we engineered constitutive mTORC1 activation in prostate epithelium by a conditional genetic deletion of tuberous sclerosis complex 1 (Tsc1) , a potent negative regulator of mTORC1 signaling
Zeng et al., Hum Mol Genet 2011 (Disease Models, Animal...) : These findings provide novel evidence in mouse models that Tsc2 mutations intrinsically cause a more severe neurological phenotype than Tsc1 mutations and suggest that the difference in phenotype may be related to the degree to which Tsc1 and Tsc2 inactivation causes abnormal mTOR activation
Sun et al., Proc Natl Acad Sci U S A 2011 (Neoplasms) : PKM2 level was augmented in mouse kidney tumors due to deficiency of tuberous sclerosis complex 2 and consequent mTOR activation , and was reduced in human cancer cells by mTOR suppression
Wolff et al., Mol Cell Biol 2011 (Anoxia) : We previously reported that mTORC1 regulation by hypoxia involves Redd1 and the Tsc1/Tsc2 complex
Tomasoni et al., Biochem Soc Trans 2011 (Tuberous Sclerosis) : In the present paper, we review recent evidence highlighting the notion that the TSC1/2 complex simultaneously controls mTOR dependent and mTOR independent signals critical for the balancing of cell proliferation and cell death
Wu et al., J Immunol 2011 (Lymphopenia) : 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 cellularity, especially within the CD8 subset
Yang et al., Nat Immunol 2011 : Therefore, Tsc1 dependent control of mTOR is crucial in actively maintaining the quiescence of naive T cells to facilitate adaptive immune function
Yoshida et al., J Biol Chem 2011 : Taken together, our results suggest that the TSC complex plays an important role in redox-sensitive mTORC1 regulation and argues for the activation of mTORC1 in places other than the lysosome upon inhibition of the TSC complex
O'Brien et al., Eur J Immunol 2011 : The TSC1/TSC2 complex has been shown to inhibit mTORC1 signaling in cell line models ... Overall, our results demonstrate that TSC1 differentially regulates mTORC1 and mTORC2 activity, promotes T-cell survival, and is critical for normal mitochondrial homeostasis in T cells ... Overall, our results demonstrate that TSC1 differentially regulates mTORC1 and mTORC2 activity, promotes T-cell survival, and is critical for normal mitochondrial homeostasis in T cells
Zhang et al., PloS one 2012 : However, the role of TSC1 , a critical negative regulator of mTOR , in peripheral T cell homeostasis remains elusive
O'Brien et al., Arch Immunol Ther Exp (Warsz) 2012 (MAP Kinase Signaling System) : Furthermore, we highlight the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling
Tsai et al., Nature 2012 (Tuberous Sclerosis) : Tuberous 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
Tanwar et al., PLoS Genet 2012 (Adenoma...) : Deletion of the genes for Tuberous Sclerosis 1 (Tsc1) or Tsc2, regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1 deleted stroma contributes to the phenotype
Iyer et al., Science 2012 (Neoplasm Metastasis...) : Among the somatic mutations was a loss-of-function mutation in TSC1 ( tuberous sclerosis complex 1 ), a regulator of mTOR pathway activation
Zhang et al., Breast Cancer Res Treat 2012 (Breast Neoplasms) : Disruption of mTOR-Raptor complex and activation of AMPK/TSC signaling may contribute to inhibitory effects of NDGA against mTORC1
Kenerson et al., Gastroenterology 2013 (Carcinoma, Hepatocellular...) : In livers of albumin (Alb)-Cre mice, we selectively deleted tuberous sclerosis (Tsc)1 , a negative regulator of Ras homolog enriched in brain and mTORC1 , along with Phosphatase and tensin homolog (Pten), a negative regulator of PI3K
Guo et al., Mol Cancer Res 2013 : Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1
Melnik et al., Exp Dermatol 2013 : Suppression of TNFa signalling by tetracyclines, erythromycin and other macrolides may attenuate IKKß-TSC1 mediated mTORC1 activation