2024
PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals
Wang S, Di Y, Yang Y, Salovska B, Li W, Hu L, Yin J, Shao W, Zhou D, Cheng J, Liu D, Yang H, Liu Y. PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals. Cell Reports Methods 2024, 4: 100859. PMID: 39255793, PMCID: PMC11440062, DOI: 10.1016/j.crmeth.2024.100859.Peer-Reviewed Original ResearchConceptsP-siteSurrounding amino acid sequenceKinase-substrate networkQuantitative phosphoproteomic analysisFunctional enrichment analysisPhosphoproteomic resultsKinase motifsComparative phosphoproteomicsPTM sitesPhosphorylation eventsPhosphoproteomic analysisProteomic analysisEnrichment analysisMammalian speciesSpeciesEvolutionary anglePhosphoproteomeMotifEnvironmental factorsNon-human speciesPTMProteomicsKinaseMammalsProteinTargeting TREX1 induces innate immune response in drug-resistant Small Cell Lung Cancer
Murayama T, Mahadevan N, Meador C, Ivanova E, Pan Y, Knelson E, Tani T, Nakayama J, Ma X, Thai T, Hung Y, Kim W, Watanabe H, Cai K, Hata A, Paweletz C, Barbie D, Cañadas I. Targeting TREX1 induces innate immune response in drug-resistant Small Cell Lung Cancer. Cancer Research Communications 2024, 4: 2399-2414. PMID: 39177280, PMCID: PMC11391691, DOI: 10.1158/2767-9764.crc-24-0360.Peer-Reviewed Original ResearchConceptsSmall-cell lung cancerPatient-derived xenograftsCells to chemotherapyLung cancerInnate immune responseImmune responseSmall cell lung cancerHuman SCLC tumorsSurvival of resistant cellsResponse to chemotherapyCell lung cancerEfficacy of chemotherapyRepair exonuclease 1Postchemotherapy samplesAntitumor immunitySCLC tumorsCold tumorsAvailable therapiesChromatin immunoprecipitation sequencingTransposase-accessible chromatinInduce immunogenicityChemotherapyResistant cellsTherapeutic strategiesTREX1 expressionSubunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes
Jann J, Hergott C, Winkler M, Liu Y, Braun B, Charles A, Copson K, Barua S, Meggendorfer M, Nadarajah N, Shimony S, Winer E, Wadleigh M, Stone R, DeAngelo D, Garcia J, Haferlach T, Lindsley R, Luskin M, Stahl M, Tothova Z. Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes. Leukemia 2024, 38: 1992-2002. PMID: 39033241, PMCID: PMC11347381, DOI: 10.1038/s41375-024-02347-y.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaDana-Farber Cancer InstituteMyelodysplastic neoplasmsCohesin complex componentSubunit specificityAssociated with secondary AMLCohesin complexDe novo acute myeloid leukemiaSecondary acute myeloid leukemiaComplex mutationsCohesinGenetic driversGenetic characteristicsSTAG2 mutationsCo-occurrenceSubunit mutationsMutationsMyeloid malignanciesPrognostic significanceAdverse prognosisPrognostic classificationMyeloid leukemiaClinical characteristicsDana-FarberOntogenyLymphocyte Phosphatase-Associated Phosphoprotein (LPAP) as a CD45 Protein Stability Regulator
Kruglova N, Mazurov D, Filatov A. Lymphocyte Phosphatase-Associated Phosphoprotein (LPAP) as a CD45 Protein Stability Regulator. Biochemistry (Moscow) 2024, 89: 912-922. PMID: 38880651, DOI: 10.1134/s0006297924050110.Peer-Reviewed Original ResearchConceptsLymphocyte phosphatase-associated phosphoproteinExpression level of CD45Protein stability regulationSurface expression of CD45Expression of CD45Levels of CD45Binding partnersPhosphatase CD45Lymphoid cellsLymphocyte activationCD45 proteinSurface expressionCD45Biochemical evidenceK562 cellsStability regulationLymphocytesPhosphoproteinNetwork-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis
Rosenberger G, Li W, Turunen M, He J, Subramaniam P, Pampou S, Griffin A, Karan C, Kerwin P, Murray D, Honig B, Liu Y, Califano A. Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis. Nature Communications 2024, 15: 3909. PMID: 38724493, PMCID: PMC11082183, DOI: 10.1038/s41467-024-47957-3.Peer-Reviewed Original ResearchConceptsMechanism of cell responseResistance mechanismsSignaling pathway responsesDrug resistance mechanismsEnzyme/substrate interactionsAdaptive resistance mechanismsNetwork rewiringPhosphorylation stateSignaling pathway activationDrug perturbationsProteomic technologiesSignaling crosstalkPathway responsesInhibitor designPathway activationCancer drug resistance mechanismsCell adaptive responsesAdaptive responsePhosphatase activityNetwork-based methodologyRewiringTherapeutic efficacyPhosphoproteome coverageCell responsesControl medium
2023
“Double‐hit” ineffective erythropoiesis—concurrent β‐thalassemia with α‐gene triplication and myelodysplastic syndrome with SF3B1 mutation
Chen P, Gorshein E, Tormey C, Siddon A, Perincheri S. “Double‐hit” ineffective erythropoiesis—concurrent β‐thalassemia with α‐gene triplication and myelodysplastic syndrome with SF3B1 mutation. American Journal Of Hematology 2023, 98: 984-988. PMID: 36688500, DOI: 10.1002/ajh.26856.Peer-Reviewed Educational MaterialsAn atlas of substrate specificities for the human serine/threonine kinome
Johnson J, Yaron T, Huntsman E, Kerelsky A, Song J, Regev A, Lin T, Liberatore K, Cizin D, Cohen B, Vasan N, Ma Y, Krismer K, Robles J, van de Kooij B, van Vlimmeren A, Andrée-Busch N, Käufer N, Dorovkov M, Ryazanov A, Takagi Y, Kastenhuber E, Goncalves M, Hopkins B, Elemento O, Taatjes D, Maucuer A, Yamashita A, Degterev A, Uduman M, Lu J, Landry S, Zhang B, Cossentino I, Linding R, Blenis J, Hornbeck P, Turk B, Yaffe M, Cantley L. An atlas of substrate specificities for the human serine/threonine kinome. Nature 2023, 613: 759-766. PMID: 36631611, PMCID: PMC9876800, DOI: 10.1038/s41586-022-05575-3.Peer-Reviewed Original ResearchConceptsSer/ThrHuman Ser/ThrSubstrate specificityPhosphorylation eventsProtein serine/threonine kinaseWidespread post-translational modificationSerine/threonine kinasePutative protein kinaseSubstrate sequence specificityIntrinsic substrate specificityPost-translational modificationsThreonine phosphorylationGenetic perturbationsThreonine kinasePhosphorylation sitesHuman genomeProtein phosphorylationProtein kinaseSequence specificityBiological pathwaysHuman diseasesNegative selectivityKinaseUnexpected insightsKinome
2022
Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations
Choudhary GS, Pellagatti A, Agianian B, Smith MA, Bhagat TD, Gordon-Mitchell S, Sahu S, Pandey S, Shah N, Aluri S, Aggarwal R, Aminov S, Schwartz L, Steeples V, Booher RN, Ramachandra M, Samson M, Carbajal M, Pradhan K, Bowman TV, Pillai MM, Will B, Wickrema A, Shastri A, Bradley RK, Martell RE, Steidl UG, Gavathiotis E, Boultwood J, Starczynowski DT, Verma A. Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations. ELife 2022, 11: e78136. PMID: 36040792, PMCID: PMC9427103, DOI: 10.7554/elife.78136.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeNF-kB activationLymphoma SocietyMDS/acute myeloid leukemiaNational InstitutePathogenesis of MDSInterleukin-1 receptor-associated kinase 4Expression of IRAK4Inflammatory-immune pathwaysInflammatory cytokine productionSpecific oncogenic pathwaysCareer development grantsHealth research trainingCritical downstream mediatorCytokine productionMyeloid leukemiaPreclinical modelsNew York State DepartmentXenograft modelImmune pathwaysNF-kB.MDS samplesTRAF6 activationLeukemic growthTargeting the EIF2AK1 signaling pathway rescues red blood cell production in SF3B1-mutant myelodysplastic syndromes with ringed sideroblasts
Adema V, Ma F, Kanagal-Shamanna R, Thongon N, Montalban-Bravo G, Yang H, Peslak SA, Wang F, Acha P, Sole F, Lockyer P, Cassari M, Maciejewski JP, Visconte V, Ganan-Gomez I, Song Y, Bueso-Ramos C, Pellegrini M, Tan TM, Bejar R, Carew JS, Halene S, Santini V, Al-Atrash G, Clise-Dwyer K, Garcia-Manero G, Blobel GA, Colla S. Targeting the EIF2AK1 signaling pathway rescues red blood cell production in SF3B1-mutant myelodysplastic syndromes with ringed sideroblasts. Blood Cancer Discovery 2022, 3: 554-567. PMID: 35926182, PMCID: PMC9894566, DOI: 10.1158/2643-3230.bcd-21-0220.Peer-Reviewed Original ResearchMeSH KeywordsAgedeIF-2 KinaseErythroid Precursor CellsHumansMyelodysplastic SyndromesPhosphoproteinsRNA Splicing FactorsSignal TransductionConceptsMyelodysplastic syndromeRed blood cell productionSF3B1-mutant myelodysplastic syndromesMDS-RSRinged sideroblastsBlood cell productionSF3B1 mutationsDevelopment of therapiesCell productionRed blood cellsRed blood cell maturationHematologic responseSignificant anemiaTransfusion dependencyIron overloadMDS subtypesElderly populationSide effectsBone marrowCell maturationIssue featurePatientsBlood cellsErythroid precursorsBlood cell maturationInterferon activated gene 204 protects against bone loss in experimental periodontitis
Swanson KV, Girnary M, Alves T, Ting JP, Divaris K, Beck J, Pucinelli CM, da Silva RAB, Uyan D, Wilson JE, Seaman WT, Webster‐Cyriaque J, Vias N, Jiao Y, Cantley L, Marlier A, Arnold RR, Marchesan JT. Interferon activated gene 204 protects against bone loss in experimental periodontitis. The Journal Of Periodontology 2022, 93: 1366-1377. PMID: 35404474, PMCID: PMC9489626, DOI: 10.1002/jper.21-0668.Peer-Reviewed Original ResearchConceptsBone lossHuman endothelial cellsOsteoclast numberPeriodontal pathogensRecent human genetic association studiesHigher alveolar bone lossEndothelial cellsPeriodontal disease biomarkersAlveolar bone lossNeutrophils/macrophagesInterferon gamma-inducible protein 16Inflammatory cell traffickingInducible protein 16Periodontitis developmentChemokine responsesExperimental periodontitisInflammatory infiltrationPeriodontal destructionMarrow sourcesGingival tissuesMelanoma 2Periodontal tissuesLigature modelChimeric miceAlveolar boneSugar, Fat, and YAP: A Recipe for Vascular Stiffness
Mani A, Hwa J, Martin KA. Sugar, Fat, and YAP: A Recipe for Vascular Stiffness. Circulation Research 2022, 130: 868-870. PMID: 35298300, PMCID: PMC9112226, DOI: 10.1161/circresaha.122.320880.Peer-Reviewed Original ResearchSex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine
Saland SK, Wilczak K, Voss E, Lam TT, Kabbaj M. Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine. Scientific Reports 2022, 12: 1820. PMID: 35110693, PMCID: PMC8810966, DOI: 10.1038/s41598-022-05937-x.Peer-Reviewed Original ResearchConceptsLow-dose ketamineFemale ratsMale ratsTherapeutic effectIntact adult male ratsNMDA receptor antagonist ketamineAcute low doseKetamine's therapeutic effectsRapid antidepressant actionsAdult male ratsKetamine-induced changesRapid actionAntidepressant actionAntidepressant ketamineHormonal milieuHormone-dependent modulationHormonal statusLow doseKetamineBrain regionsRatsSynaptic signalingPathway activationBi-directional effectsCritical modulatorRecognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules
Stravalaci M, Pagani I, Paraboschi E, Pedotti M, Doni A, Scavello F, Mapelli S, Sironi M, Perucchini C, Varani L, Matkovic M, Cavalli A, Cesana D, Gallina P, Pedemonte N, Capurro V, Clementi N, Mancini N, Invernizzi P, Bayarri-Olmos R, Garred P, Rappuoli R, Duga S, Bottazzi B, Uguccioni M, Asselta R, Vicenzi E, Mantovani A, Garlanda C. Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules. Nature Immunology 2022, 23: 275-286. PMID: 35102342, DOI: 10.1038/s41590-021-01114-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsC-Reactive ProteinCase-Control StudiesChlorocebus aethiopsComplement ActivationCoronavirus Nucleocapsid ProteinsCOVID-19FemaleGlycosylationHEK293 CellsHost-Pathogen InteractionsHumansImmunity, HumoralMaleMannose-Binding LectinPhosphoproteinsPolymorphism, GeneticProtein BindingReceptors, Pattern RecognitionSARS-CoV-2Serum Amyloid P-ComponentSignal TransductionSpike Glycoprotein, CoronavirusVero CellsConceptsFluid phase pattern recognition moleculesPattern recognition moleculesHumoral fluid phase pattern recognition moleculesMannose-binding lectinSARS-CoV-2Pentraxin 3Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Spike proteinDisease severity biomarkersSyndrome coronavirus 2Coronavirus disease 2019Long pentraxin 3Antibody-like functionsVariants of concernRecognition moleculesHumoral armSeverity biomarkersCoronavirus 2Disease 2019Innate immunityDisease severityComplement activationTranslational implications
2021
MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells
Jeong J, Shin JH, Li W, Hong JY, Lim J, Hwang JY, Chung JJ, Yan Q, Liu Y, Choi J, Wysolmerski J. MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells. Cell Reports 2021, 37: 110160. PMID: 34965434, PMCID: PMC8762588, DOI: 10.1016/j.celrep.2021.110160.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBreast NeoplasmsCell ProliferationCytoskeletal ProteinsDrug Resistance, NeoplasmEndocytosisFemaleHumansMembrane MicrodomainsMyelin and Lymphocyte-Associated Proteolipid ProteinsPhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2Sodium-Hydrogen ExchangersTrastuzumabTumor Cells, CulturedConceptsLipid raft formationBreast cancer cellsLipid raftsLipid raft resident proteinsCancer cellsRaft formationRaft-resident proteinsProximity ligation assayProtein complexesMembrane protrusionsProtein interactionsPlasma membraneLigation assayMAL2Membrane stabilityStructural organizationPotential therapeutic targetPhysical interactionMembrane retentionProteinRaftsTherapeutic targetCellsIntracellular calcium concentrationLow intracellular calcium concentrationModulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs)
Chen PH, Hu Z, An E, Okeke I, Zheng S, Luo X, Gong A, Jaime-Figueroa S, Crews CM. Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs). ACS Chemical Biology 2021, 16: 2808-2815. PMID: 34780684, PMCID: PMC10437008, DOI: 10.1021/acschembio.1c00693.Peer-Reviewed Original ResearchConceptsSer/Thr phosphataseChemical biology approachPP2A holoenzymeProtein dephosphorylationBiology approachProtein substratesTranscriptional activationProtein phosphorylationCatalytic subunitCell biologyReporter geneProtein activityRetinoblastoma proteinOff-target effectsCritical proteinsDephosphorylationTernary complexPhosphorylationKinase inhibitorsFOXO3aPROTACsProteinChimerasPhosphataseDrug resistanceDyrk1b promotes autophagy during skeletal muscle differentiation by upregulating 4e-bp1
Bhat N, Narayanan A, Fathzadeh M, Shah K, Dianatpour M, Abou Ziki MD, Mani A. Dyrk1b promotes autophagy during skeletal muscle differentiation by upregulating 4e-bp1. Cellular Signalling 2021, 90: 110186. PMID: 34752933, PMCID: PMC8712395, DOI: 10.1016/j.cellsig.2021.110186.Peer-Reviewed Original ResearchConceptsSkeletal muscle differentiationMuscle differentiationC2C12 cellsHuman skeletal muscle developmentSkeletal muscle developmentGlobal gene networksPost-transcriptional targetEmbryonic lethalGene networksZebrafish embryosMyofiber differentiationOverexpression approachesMuscle developmentCRISPR/DYRK1BRare gainDownstream targetsTranslational inhibitorKey regulatorUntargeted proteomicsFunction mutationsAutophagic fluxEnhances AutophagyDifferentiationAutophagySymptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination
Marshall M, Ferguson ID, Lewis P, Jaggi P, Gagliardo C, Collins JS, Shaughnessy R, Caron R, Fuss C, Corbin KJE, Emuren L, Faherty E, Hall EK, Di Pentima C, Oster ME, Paintsil E, Siddiqui S, Timchak DM, Guzman-Cottrill JA. Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination. Pediatrics 2021, 148: e2021052478. PMID: 34088762, DOI: 10.1542/peds.2021-052478.Peer-Reviewed Original ResearchConceptsPfizer-BioNTech COVID-19 vaccinationCOVID-19 vaccinationAcute myocarditisClinical courseLate gadolinium enhancement (LGE) characteristicsPolymerase chain reaction test resultsTranscription polymerase chain reaction (RT-PCR) test resultsVaccine Adverse Event Reporting SystemCoronavirus disease 2019 (COVID-19) vaccinationAcute COVID-19Multisystem inflammatory syndromeAdverse Event Reporting SystemImportant adverse eventsTime of presentationNonsteroidal antiinflammatory drugsHealthy male adolescentsGadolinium enhancement characteristicsEvent Reporting SystemReaction test resultsChest painElevated troponinInflammatory syndromeIntravenous immunoglobulinAdverse eventsSecond doseData-independent acquisition-based proteome and phosphoproteome profiling across six melanoma cell lines reveals determinants of proteotypes
Gao E, Li W, Wu C, Shao W, Di Y, Liu Y. Data-independent acquisition-based proteome and phosphoproteome profiling across six melanoma cell lines reveals determinants of proteotypes. Molecular Omics 2021, 17: 413-425. PMID: 33728422, PMCID: PMC8205956, DOI: 10.1039/d0mo00188k.Peer-Reviewed Original ResearchSPLUNC1: a novel marker of cystic fibrosis exacerbations
Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. SPLUNC1: a novel marker of cystic fibrosis exacerbations. European Respiratory Journal 2021, 58: 2000507. PMID: 33958427, PMCID: PMC8571118, DOI: 10.1183/13993003.00507-2020.Peer-Reviewed Original ResearchConceptsAcute pulmonary exacerbationsSPLUNC1 levelsCystic fibrosisClinical outcomesCF participantsLong-term disease controlNasal epithelium clone 1Cystic fibrosis exacerbationsHigher AE riskLung function declineCytokines interleukin-1βTumor necrosis factorAE riskClinical worseningPulmonary exacerbationsStable patientsLung functionAirway clearanceFunction declineSputum collectionAcute inflammationInflammatory cytokinesMicrobiology findingsCF careClinical managementEpigenomic Profiles of African-American Transthyretin Val122Ile Carriers Reveals Putatively Dysregulated Amyloid Mechanisms
Pathak GA, Wendt FR, De Lillo A, Nunez YZ, Goswami A, De Angelis F, Fuciarelli M, Kranzler HR, Gelernter J, Polimanti R. Epigenomic Profiles of African-American Transthyretin Val122Ile Carriers Reveals Putatively Dysregulated Amyloid Mechanisms. Circulation Genomic And Precision Medicine 2021, 14: e003011. PMID: 33428857, PMCID: PMC7887108, DOI: 10.1161/circgen.120.003011.Peer-Reviewed Original ResearchAmyloidosisATP Binding Cassette Transporter 1Black or African AmericanDNA MethylationEpigenomicsGene Regulatory NetworksGenome-Wide Association StudyHeart DiseasesHumansKv1.6 Potassium ChannelPhosphoproteinsPolymorphism, Single NucleotidePrealbuminQuantitative Trait LociUbiquitin-Conjugating Enzymes
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