Search results for "Mechanistic Target of Rapamycin Complex 1"

showing 6 items of 16 documents

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

2014

// Nicole M. Davis 1 , Melissa Sokolosky 1 , Kristin Stadelman 1 , Stephen L. Abrams 1 , Massimo Libra 2 , Saverio Candido 2 , Ferdinando Nicoletti 2 , Jerry Polesel 3 , Roberta Maestro 4 , Antonino D’Assoro 5 , Lyudmyla Drobot 6 , Dariusz Rakus 7 , Agnieszka Gizak 7 , Piotr Laidler 8 , Joanna Dulinska-Litewka 8 , Joerg Basecke 9 , Sanja Mijatovic 10 , Danijela Maksimovic-Ivanic 10 , Giuseppe Montalto 11,12 , Melchiorre Cervello 12 , Timothy L. Fitzgerald 13 , Zoya N. Demidenko 14 , Alberto M. Martelli 15 , Lucio Cocco 15 , Linda S. Steelman 1 and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858 USA 2 …

Oncologymedicine.medical_specialtytherapy resistanceClass I Phosphatidylinositol 3-Kinasesmedicine.medical_treatmentBreast NeoplasmsReviewBiologyMechanistic Target of Rapamycin Complex 1PI3KMetastasisTargeted therapyPhosphatidylinositol 3-KinasesBreast cancerTARGETED THERAPYInternal medicinemedicinePTENHumansTargeted Therapy Therapy Resistance Mutations PI3K mTOR rapamycinskin and connective tissue diseasesProtein kinase BneoplasmsPI3K/AKT/mTOR pathwayRoswell Park Cancer InstituterapamycinTOR Serine-Threonine KinasesMTORPTEN PhosphohydrolaseCancerTargeted TherapyTherapy Resistancemedicine.diseaseTargeted Therapy; Therapy Resistance; Mutations; PI3K; mTOR; rapamycin3. Good healthErbB ReceptorsGene Expression Regulation NeoplasticOncologyMultiprotein ComplexesCancer researchbiology.proteinFemaleReceptor Epidermal Growth FactormutationRAPAMYCINProto-Oncogene Proteins c-aktMutationsSignal Transduction
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Promoter architecture and transcriptional regulation of Abf1-dependent ribosomal protein genes inSaccharomyces cerevisiae

2016

In Saccharomyces cerevisiae, ribosomal protein gene (RPG) promoters display binding sites for either Rap1 or Abf1 transcription factors. Unlike Rap1-associated promoters, the small cohort of Abf1-dependent RPGs (Abf1-RPGs) has not been extensively investigated. We show that RPL3, RPL4B, RPP1A, RPS22B and RPS28A/B share a common promoter architecture, with an Abf1 site upstream of a conserved element matching the sequence recognized by Fhl1, a transcription factor which together with Ifh1 orchestrates Rap1-associated RPG regulation. Abf1 and Fhl1 promoter association was confirmed by ChIP and/or gel retardation assays. Mutational analysis revealed a more severe requirement of Abf1 than Fhl1 …

Ribosomal Proteins0301 basic medicineSaccharomyces cerevisiae ProteinsTranscription GeneticTelomere-Binding ProteinsRibosome biogenesisSaccharomyces cerevisiaeMechanistic Target of Rapamycin Complex 1Biology03 medical and health sciencesRibosomal proteinTranscription (biology)Gene Expression Regulation FungalGeneticsTranscriptional regulationBinding sitePromoter Regions GeneticTranscription factorGeneGeneticsBinding SitesTOR Serine-Threonine KinasesGene regulation Chromatin and EpigeneticsForkhead Transcription FactorsPromoterDNA-Binding Proteins030104 developmental biologyMultiprotein ComplexesTrans-ActivatorsTranscription FactorsNucleic Acids Research
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In human endothelial cells rapamycin causes mTORC2 inhibition and impairs cell viability and function.

2008

Aim Drug-eluting stents are widely used to prevent restenosis but are associated with late endothelial damage. To understand the basis for this effect, we have studied the consequences of a prolonged incubation with rapamycin on the viability and functions of endothelial cells. Methods and results Human umbilical vein or aorta endothelial cells were exposed to rapamycin in the absence or in the presence of tumour necrosis factor α (TNFα). After a 24 h-incubation, rapamycin (100 nM) caused a significant cell loss associated with the increase of both apoptosis and necrosis, as quantified by propidium iodide staining, caspase 3 activity, and lactate dehydrogenase release. Rapamycin also impair…

Time FactorsPhysiologyApoptosismTORC1Polymerase Chain Reactionchemistry.chemical_compoundCell MovementStress FibersMicroscopy ConfocalCaspase 3TOR Serine-Threonine KinasesNitric Oxide Synthase Type IIIRibosomal Protein S6 Kinases 70-kDaUp-RegulationEndothelial stem cellmedicine.anatomical_structureBiochemistryCardiology and Cardiovascular MedicineE-SelectinEndotheliumNitric Oxide Synthase Type IIICell SurvivalBlotting WesternEnzyme-Linked Immunosorbent AssayBiologyMechanistic Target of Rapamycin Complex 1Nitric OxideTacrolimusNecrosisTheophyllinePhysiology (medical)medicineHumansImmunoprecipitationViability assayPropidium iodideProtein kinase BAdaptor Proteins Signal TransducingSirolimusDose-Response Relationship DrugL-Lactate DehydrogenaseTumor Necrosis Factor-alphaEndothelial CellsProteinsCardiovascular AgentsRegulatory-Associated Protein of mTORMolecular biologyRapamycin-Insensitive Companion of mTOR ProteinchemistryMultiprotein ComplexesTOR Serine-Threonine KinasesCarrier ProteinsProtein KinasesTranscription FactorsCardiovascular research
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mTOR Driven Gene Transcription Is Required for Cholesterol Production in Neurons of the Developing Cerebral Cortex

2021

AbstractDysregulated mammalian target of rapamycin (mTOR) activity is associated with various neurodevelopmental disorders ranging from idiopathic autism spectrum disorders to syndromes caused by single gene defects. This suggests that maintaining mTOR activity levels in a physiological range is essential for brain development and functioning. Upon activation, mTOR regulates a variety of cellular processes such as cell growth, autophagy and metabolism. On a molecular level, however, the consequences of mTOR activation in the brain are not well understood.Low levels of cholesterol are associated with a wide variety of neurodevelopmental disorders. We here describe numerous genes of the stero…

Transcription GeneticQH301-705.5Primary Cell CulturemTORC1Mechanistic Target of Rapamycin Complex 1BiologySREBPCatalysisArticleInorganic ChemistryMiceAutophagyTranscriptional regulationmedicineAnimalsPhysical and Theoretical ChemistryBiology (General)Molecular BiologyTranscription factorQD1-999mTORC1SpectroscopyPI3K/AKT/mTOR pathwayCerebral CortexNeuronsSterol Regulatory Element Binding ProteinsCell growthTOR Serine-Threonine KinasesOrganic Chemistrycholesterol ; NF-Y ; neurogenesis ; mTOR ; mTORC1 ; SP1 ; SREBPAutophagyGene Expression Regulation DevelopmentalcholesterolGeneral MedicineComputer Science ApplicationsSterol regulatory element-binding proteinCell biologySP1Chemistryneurogenesismedicine.anatomical_structureCCAAT-Binding FactorCerebral cortexmTORNF-YProtein KinasesSignal TransductionInternational Journal of Molecular Sciences
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The deubiquitinase USP11 is a versatile and conserved regulator of autophagy

2021

Autophagy is a major cellular quality control system responsible for the degradation of proteins and organelles in response to stress and damage to maintain homeostasis. Ubiquitination of autophagy-related proteins or regulatory components is important for the precise control of autophagy pathways. Here, we show that the deubiquitinase ubiquitin-specific protease 11 (USP11) restricts autophagy and that KO of USP11 in mammalian cells results in elevated autophagic flux. We also demonstrate that depletion of the USP11 homolog H34C03.2 in Caenorhabditis elegans triggers hyperactivation of autophagy and protects the animals against human amyloid-β peptide 42 aggregation-induced paralysis. USP11…

autophagyhAβ42 human amyloid-β protein 1 to 42Lipid kinase activityPI(3)P phosphatidylinositol-3-phosphatemTORC1BiochemistryCell LineGene Knockout Techniqueschemistry.chemical_compoundubiquitinAnimalsHumansULK1 unc-51-like autophagy activating kinase 1WIPI WD-repeat domain phosphoinositide-interacting proteinPI3KC3-C1Caenorhabditis elegansCaenorhabditis elegans ProteinsmTORC1Molecular BiologyMechanistic target of rapamycinUSP11 ubiquitin-specific protease 11proteostasisAmyloid beta-PeptidesS6K S6 kinasebiologyPhosphatidylinositol 3-phosphateAutophagyDUB deubiquitinaseLFQ label-free quantificationIP immunoprecipitationNHT nonhuman targetingPI3KC3-C1 class III phosphatidylinositol 3-kinase complex ICell BiologyACN acetonitrileAβ amyloid-βNRBF2 nuclear receptor-binding factor 2Peptide FragmentsCell biologydeubiquitinase (DUB)ProteostasischemistryProteotoxicitymTORC1 mechanistic target of rapamycin complex 1biology.proteinAutophagy-Related Protein-1 HomologBSA bovine serum albuminThiolester HydrolasesResearch ArticleJournal of Biological Chemistry
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MTOR inhibitor-based combination therapies for pancreatic cancer

2018

Background: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. Methods: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pha…

therapeutic resistance0301 basic medicineCancer ResearchCell SurvivalMAP Kinase Signaling Systempancreatic cancerAntineoplastic AgentsContext (language use)Mechanistic Target of Rapamycin Complex 2mTORC1Mechanistic Target of Rapamycin Complex 1BiologymTORC2BortezomibMice03 medical and health sciencesCell Line TumorPancreatic cancermedicineAnimalsHumansExtracellular Signal-Regulated MAP KinasesMechanistic target of rapamycinPI3K/AKT/mTOR pathwayBenzoxazolesKinaseMTORTOR Serine-Threonine Kinasesmedicine.diseaseddc:3. Good healthPancreatic NeoplasmsPyrimidines030104 developmental biologyOncologybiology.proteinCancer researchCamptothecinTOR Serine-Threonine KinasesPhosphatidylinositol 3-KinaseTranslational TherapeuticsProto-Oncogene Proteins c-aktBiologieCarcinoma Pancreatic Ductal
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