TSC2 Deficiency Increases PTEN via HIF1α [PDF]
Journal of Biological Chemistry, 2009 Substantial evidence suggests roles of TSC2 and PTEN in the development of cancer predisposition syndromes. Loss of TSC2 results in benign tumors, neurological disorders, and angiomyolipomas. We found that PTEN mRNA and protein levels are elevated in Tsc2(-/-) mouse embryo fibroblasts with concomitant reduction in Akt phosphorylation. Reconstitution of
Lenin, Mahimainathan +9 more
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Akt phosphorylates both Tsc1 and Tsc2 in Drosophila, but neither phosphorylation is required for normal animal growth. [PDF]
PLoS ONE, 2009 Akt, an essential component of the insulin pathway, is a potent inducer of tissue growth. One of Akt's phosphorylation targets is Tsc2, an inhibitor of the anabolic kinase TOR. This could account for part of Akt's growth promoting activity.
Sibylle Schleich, Aurelio A Teleman
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Class III PI3K regulates organismal glucose homeostasis by providing negative feedback on hepatic insulin signalling. [PDF]
, 2015 Defective hepatic insulin receptor (IR) signalling is a pathogenic manifestation of metabolic disorders including obesity and diabetes. The endo/lysosomal trafficking system may coordinate insulin action and nutrient homeostasis by endocytosis of IR and ...
Burnol, Anne-Françoise +7 more
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eLife, 2017 Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud ...
Peter J Klover +14 more
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Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy. [PDF]
, 2016 Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II ...
Falchook, Gerald S. +17 more
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Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options. [PDF]
, 2014 Seizures are clinically significant manifestations associated with 79%-90% of patients with tuberous sclerosis complex. Often occurring within the first year of life in the form of infantile spasms, seizures interfere with neuropsychiatric, social, and ...
Fallah, Aria, Wang, Shelly
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The Methylation of the TSC2 Promoter Underlies the Abnormal Growth of TSC2 Angiomyolipoma-Derived Smooth Muscle Cells [PDF]
The American Journal of Pathology, 2009 Tuberous sclerosis complex (TSC) is an autosomal-dominant disease that is caused by mutations in either the TSC1 or TSC2 gene. 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. The cells bear a
E. Lesma +8 more
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Biological aspects of mTOR in leukemia [PDF]
, 2018 The mammalian target of rapamycin (mTOR) is a central processor of intra-and extracellular signals, regulating many fundamental cellular processes such as metabolism, growth, proliferation, and survival.
Bianchi, Mp +5 more
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GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling [PDF]
, 2015 The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell ...
Alan Prescott +60 more
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Carboxy terminal tail of polycystin-1 regulates localization of TSC2 to repress mTOR. [PDF]
PLoS ONE, 2010 Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited renal disorder caused by defects in the PKD1 or PKD2 genes. ADPKD is associated with significant morbidity, and is a major underlying cause of end-stage renal failure (ESRF ...
Ruhee Dere +3 more
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