2018
Ganetespib limits ciliation and cystogenesis in autosomal‐dominant polycystic kidney disease (ADPKD)
Nikonova AS, Deneka AY, Kiseleva AA, Korobeynikov V, Gaponova A, Serebriiskii IG, Kopp MC, Hensley HH, Seeger‐Nukpezah T, Somlo S, Proia DA, Golemis EA. Ganetespib limits ciliation and cystogenesis in autosomal‐dominant polycystic kidney disease (ADPKD). The FASEB Journal 2018, 32: 2735-2746. PMID: 29401581, PMCID: PMC5901382, DOI: 10.1096/fj.201700909r.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseEnd-stage renal diseaseLoss of Pkd1Conditional mouse modelHeat shock protein-90 clientsRenal diseaseKidney enlargementClinical Hsp90 inhibitorsRenal cystsAmeliorated symptomsMouse modelNew biologic activityCiliary lossCystic growthDiseaseBiologic activityGlycolysis inhibitorGanetespibADPKD pathogenesisVivo lossHsp90 inhibitorsHsp90 inhibitionRenal cilia
2015
Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity
Fedeles SV, So JS, Shrikhande A, Lee SH, Gallagher AR, Barkauskas CE, Somlo S, Lee AH. Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity. Journal Of Clinical Investigation 2015, 125: 1955-1967. PMID: 25844898, PMCID: PMC4463201, DOI: 10.1172/jci78863.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDisease Models, AnimalDNA HelicasesDNA-Binding ProteinsEndoribonucleasesFemaleGlucosidasesIntracellular Signaling Peptides and ProteinsKidneyMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMolecular ChaperonesPolycystic Kidney, Autosomal DominantPolycystic Kidney, Autosomal RecessiveProtein Serine-Threonine KinasesProtein Structure, TertiaryReceptors, G-Protein-CoupledRecombinant Fusion ProteinsRegulatory Factor X Transcription FactorsRNA SplicingRNA, Small InterferingRNA-Binding ProteinsTranscription FactorsTransfectionTRPP Cation ChannelsUnfolded Protein ResponseX-Box Binding Protein 1ConceptsG protein-coupled receptor proteolysis siteCyst formationPolycystic liver diseaseGPS cleavagePolycystin-1IRE1α-XBP1 branchMurine genetic modelsPolycystic kidney phenotypeLiver diseasePolycystic diseaseCystic diseaseDisease manifestationsMurine modelDisease severityKidney phenotypeXBP1 activationUnfolded protein response pathwayDiseaseXBP1 overexpressionPC1 functionsProtein response pathwayEnforced expressionMiceXBP1Activation of XBP1
2014
N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*
Hofherr A, Wagner C, Fedeles S, Somlo S, Köttgen M. N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*. Journal Of Biological Chemistry 2014, 289: 14854-14867. PMID: 24719335, PMCID: PMC4031537, DOI: 10.1074/jbc.m114.562264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAsparagineBinding SitesBlotting, WesternCell LineCells, CulturedGlucosidasesGlycosylationHEK293 CellsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsLysosomesMass SpectrometryMiceMice, KnockoutMicroscopy, FluorescenceMutationPolycystic Kidney, Autosomal DominantProtein Serine-Threonine KinasesProteolysisPyruvate Dehydrogenase Acetyl-Transferring KinaseConceptsGlucosidase IINon-catalytic β-subunitsProtein expressionFirst extracellular loopAutosomal dominant polycystic liver diseaseEfficient biogenesisGenetic interactionsMembrane proteinsBiochemical approachesN-glycosylationGenetic approachesTRPP2Glycosylation sitesBiological roleLysosomal degradationΒ-subunitChemical inhibitionBiogenesisExtracellular loopNonselective cation channelsIon channelsBiological importanceGlycosylationCation channelsProtein levels