grant
Mechanism and Significance of HMG Co-A Synthase 1 Degradation
Organization SLOAN-KETTERING INST CAN RESEARCHLocation NEW YORK, UNITED STATESPosted 7 May 2024Deadline 31 Mar 2029
NIHUS FederalResearch GrantFY202520S Catalytic Proteasome20S Core Proteasome20S Proteasome20S Proteosome21+ years old3-hydroxy-3-methylglutaryl-CoA3-hydroxy-3-methylglutaryl-coenzyme AAPF-1ATP-Dependent Proteolysis Factor 1Acetyl CoAAcetyl Coenzyme AAdultAdult HumanAmino AcidsAnti-Cancer AgentsAntineoplastic AgentsAntineoplastic DrugsAntineoplasticsAssayAttentionBioassayBiochemicalBiologicalBiological AssayBloodBlood Reticuloendothelial SystemC-terminalCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCancer DrugCancersCas nuclease technologyCell BodyCell Communication and SignalingCell Growth in NumberCell LineCell MultiplicationCell ProliferationCell SignalingCell membraneCellLineCellsCellular ExpansionCellular GrowthCellular ProliferationCholesterolClinicClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyComplexCytoplasmic MembraneCytosolDataDehydrogenasesDrug TherapyE3 LigaseE3 Ubiquitin LigaseER-associated degradation PathwayERADEndoplasmic Reticulum Degradation PathwayEnzyme GeneEnzymesEpidemiologic ResearchEpidemiologic StudiesEpidemiological StudiesEpidemiology ResearchFeedbackGatekeepingGene TranscriptionGenetic TranscriptionGrantHMG-20HMG-CoAHigh Mobility Protein 20HourHydroxylasesIn VitroIntermediary MetabolismInterruptionIntracellular Communication and SignalingKryptosterolL-ProlineLanosterolLimesMacropainMacroxyproteinaseMalignant CellMalignant NeoplasmsMalignant TumorMembraneMetabolicMetabolic ProcessesMetabolismMiceMice MammalsMixed Function OxidasesMixed Function OxygenasesModelingMolecularMonooxygenasesMulticatalytic ProteinaseMurineMusNeoplastic Disease Chemotherapeutic AgentsNutrientNutrient DepletionNutrient availabilityOxidoreductaseOxidoreductase GenePathway interactionsPharmacological TreatmentPharmacotherapyPhysiologicPhysiologicalPhysiologyPlasma MembraneProductionProlineProsomeProteasomeProteasome Endopeptidase ComplexProtein CleavageProteinsProteolysisProteomicsProteosomePublic HealthRNA ExpressionReductasesRegulationRegulatory PathwayReportingResearchRoleS-acetate Coenzyme ASignal TransductionSignal Transduction SystemsSignalingSqualeneStarvationSterolsStimulusStrains Cell LinesStressSystemTailTranscriptionTranslation ProcessTumor CellTumor-Specific Treatment AgentsUbiquitinUbiquitin Protein LigaseUbiquitin-Protein Ligase ComplexesUbiquitin-Protein Ligase E3Xenograft Modeladulthoodagedaminoacidanti-canceranti-cancer drugbiologicbiological signal transductioncancer cellcell growthcultured cell linedrug interventiondrug treatmentenvironmental changeenzyme pathwayepidemiologic investigationepidemiology studygatekeeperhydroxymethylglutaryl-CoAisoprenoidmTOR inhibitionmalignancymembrane biogenesismembrane structuremetabolism measurementmetabolomicsmetabonomicsmevalonatemulticatalytic endopeptidase complexneoplasm/cancerneoplastic cellnovelpathwaypharmaceutical interventionpharmacologicpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticsplasmalemmaprenylationreconstitutereconstitutionresponsesocial rolesterol homeostasistherapeutic targettoolubiquitin-protein ligaseuptakexenograft transplant modelxenotransplant model
Description preview
Abstract
The mevalonate pathway enzymes produce precursors of sterols and isoprenoids, essential metabolites for cell
signaling and membrane biogenesis. As such, cells employ complex transcriptional, translational, and post-
translational processes to regulate mevalonate production. Specifically, the ubiquitin proteasome system (UPS)
tightly…
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