2021
MMAB promotes negative feedback control of cholesterol homeostasis
Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando C. MMAB promotes negative feedback control of cholesterol homeostasis. Nature Communications 2021, 12: 6448. PMID: 34750386, PMCID: PMC8575900, DOI: 10.1038/s41467-021-26787-7.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAnimalsCell Line, TumorCholesterolCholesterol, LDLFeedback, PhysiologicalGene Expression ProfilingHeLa CellsHep G2 CellsHomeostasisHumansHydroxymethylglutaryl CoA ReductasesLiverMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticReceptors, LDLRNA InterferenceSterol Regulatory Element Binding Protein 2ConceptsCholesterol biosynthesisCholesterol homeostasisMouse hepatic cell lineIntegrative genomic strategyIntricate regulatory networkMaster transcriptional regulatorCellular cholesterol levelsHMGCR activityLDL-cholesterol uptakeCholesterol levelsHuman hepatic cellsSterol contentGenomic strategiesTranscriptional regulatorsRegulatory networksIntracellular cholesterol levelsGene expressionUnexpected roleHepatic cell linesBiosynthesisMMABIntracellular levelsCell linesHomeostasisExpression of SREBP2
2015
Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake
Haskins JW, Zhang S, Means RE, Kelleher JK, Cline GW, Canfrán-Duque A, Suárez Y, Stern DF. Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. Science Signaling 2015, 8: ra111. PMID: 26535009, PMCID: PMC4666504, DOI: 10.1126/scisignal.aac5124.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCholesterolFemaleHumansHydroxymethylglutaryl CoA ReductasesLipoproteins, LDLMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNeuregulin-1Proto-Oncogene Proteins c-aktReceptor, ErbB-4Receptors, LDLSterol Regulatory Element Binding Protein 2TOR Serine-Threonine KinasesConceptsIntracellular domainEGFR family membersLow-density lipoprotein uptakeCholesterol biosynthesisSREBP target genesRapamycin complex 1ErbB4 intracellular domainSite-1 proteaseCholesterol biosynthesis genesSoluble intracellular domainCholesterol biosynthetic pathwayActivation of ErbB4Mammary epithelial cellsInhibition of AktSterol regulatory elementBiosynthesis genesLipoprotein uptakeRegulatory elementsBiosynthetic pathwayTarget genesDevelopmental processesMetabolic remodelingMature formNeuregulin-1Cellular membranes
2005
Lovastatin-induced PC-12 cell differentiation is associated with RhoA/RhoA kinase pathway inactivation
Fernández-Hernando C, Suárez Y, Lasunción MA. Lovastatin-induced PC-12 cell differentiation is associated with RhoA/RhoA kinase pathway inactivation. Molecular And Cellular Neuroscience 2005, 29: 591-602. PMID: 15951198, DOI: 10.1016/j.mcn.2005.04.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCholesterolDiterpenesEnzyme ActivationEnzyme InhibitorsHydroxymethylglutaryl-CoA Reductase InhibitorsIntracellular Signaling Peptides and ProteinsLovastatinNeuritesPC12 CellsPhosphorylationProtein PrenylationProtein Serine-Threonine KinasesRatsRhoA GTP-Binding ProteinRho-Associated KinasesSterolsTerpenesConceptsNeurite outgrowthNon-sterol mevalonate derivativesPC-12 cell differentiationCellular lipid compositionNon-sterol isoprenoidsEffects of geranylgeraniolBiosynthetic pathwayProtein prenylationRole of cholesterolCofilin phosphorylationRhoA signalingMevalonate derivativesA ReductaseRhoA activationCell differentiationCoenzyme A (HMG-CoA) reductaseLovastatin inhibitsPC-12 cellsCholesterol biosynthesisPathway inactivationRhoA kinaseLipid compositionOutgrowthGeranylgeraniolInhibitionSterol stringency of proliferation and cell cycle progression in human cells
Suárez Y, Fernández C, Ledo B, Martín M, Gómez-Coronado D, Lasunción MA. Sterol stringency of proliferation and cell cycle progression in human cells. Biochimica Et Biophysica Acta 2005, 1734: 203-213. PMID: 15904877, DOI: 10.1016/j.bbalip.2005.02.003.Peer-Reviewed Original ResearchConceptsCell cycle progressionCycle progressionG2/M phaseMammalian cellsCell proliferationCell growthM phaseRegulator of proliferationSterol response elementCholesterol-free mediumPlasma membraneCell cycleResponse elementIsoprenoid derivativesStructural roleHuman cellsCholesterol biosynthesisSKF 104976Sterol analoguesDifferent sterolsHuman leukemiaCell processesCholesterol analoguesHL-60Concentration-dependent manner
2002
Inhibition of cholesterol biosynthesis by Δ22-unsaturated phytosterols via competitive inhibition of sterol Δ24-reductase in mammalian cells
FERNÁNDEZ C, SUÁREZ Y, FERRUELO AJ, GÓMEZ-CORONADO D, LASUNCIÓN MA. Inhibition of cholesterol biosynthesis by Δ22-unsaturated phytosterols via competitive inhibition of sterol Δ24-reductase in mammalian cells. Biochemical Journal 2002, 366: 109-119. PMID: 12162789, PMCID: PMC1222779, DOI: 10.1042/bj20011777.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveCaco-2 CellsCholesterolChromatography, High Pressure LiquidDose-Response Relationship, DrugHL-60 CellsHumansHypolipidemic AgentsKineticsMacrophagesMaleMiceMicrosomes, LiverModels, ChemicalOxidoreductasesPhytosterolsRatsRats, Sprague-DawleyStigmasterolTime FactorsTumor Cells, CulturedConceptsCholesterol biosynthesisCholesterol-lowering actionCholesterol-lowering agentsEffective hypocholesterolaemic agentHL-60 human cell linesRat liver microsomesIntestinal absorptionDietary phytosterolsLiver microsomesHypocholesterolaemic agentsLow intracellular concentrationsCaco-2Inhibition of sterolIncorporation of radioactivityHuman cell linesCell linesInhibitionSaturated side chainIntracellular concentrationCholesterolRelevant concentrationsRadioactivity incorporationPresent studyStrong inhibitionCompetitive inhibition
2001
Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives
Martı́nez-Botas J, Ferruelo A, Suárez Y, Fernández C, Gómez-Coronado D, Lasunción M. Dose-dependent effects of lovastatin on cell cycle progression. Distinct requirement of cholesterol and non-sterol mevalonate derivatives. Biochimica Et Biophysica Acta 2001, 1532: 185-194. PMID: 11470239, DOI: 10.1016/s1388-1981(01)00125-1.Peer-Reviewed Original ResearchConceptsCell proliferationLow-density lipoprotein cholesterolCell cycle progressionDose-dependent effectCell cycle distributionCell cycleCycle progressionLipoprotein cholesterolConcentrations of lovastatinCholesterol supplyCycle distributionCholesterolLovastatinHuman cell linesCell linesCholesterol biosynthesisCholesterol-free mediumNormal cell cyclingM phaseProgressionProliferationPresent studyHL-60Mevalonate derivativesCell cycling