Featured Publications
Nascent alt-protein chemoproteomics reveals a pre-60S assembly checkpoint inhibitor
Cao X, Khitun A, Harold CM, Bryant CJ, Zheng SJ, Baserga SJ, Slavoff SA. Nascent alt-protein chemoproteomics reveals a pre-60S assembly checkpoint inhibitor. Nature Chemical Biology 2022, 18: 643-651. PMID: 35393574, PMCID: PMC9423127, DOI: 10.1038/s41589-022-01003-9.Peer-Reviewed Original ResearchConceptsRibosomal subunitDNA damage stressImportant cellular rolesGlobal protein synthesisN-terminal extensionCellular rolesCanonical proteinsHuman cellsProtein synthesisAlternative proteinsCell proliferationChemoproteomicsDamage stressSubunitsProteinAssemblyInhibitorsHypothesis generationMicroproteinsCytoplasmProliferationCellsExportDepletionAlt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24
Cao X, Khitun A, Luo Y, Na Z, Phoodokmai T, Sappakhaw K, Olatunji E, Uttamapinant C, Slavoff SA. Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24. Nature Communications 2021, 12: 508. PMID: 33479206, PMCID: PMC7820019, DOI: 10.1038/s41467-020-20841-6.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceBase SequenceBiological TransportCell MembraneDown-RegulationEndoplasmic ReticulumHEK293 CellsHumansMembrane ProteinsMutationPhosphatidylinositol 3-KinasesPhosphatidylinositol 4,5-DiphosphateProtein BindingProto-Oncogene Proteins c-aktRibosomal ProteinsSignal TransductionTOR Serine-Threonine KinasesConceptsPI3K-AktEndoplasmic reticulumMTOR signalingHuman gene functionAlternative open reading framesOpen reading framePI3K signalingDifferent molecular mechanismsCanonical proteinsGene functionCell sizeReading framePrecursor phosphatidylinositolPlasma membraneTMEM24Upstream regulatorMolecular mechanismsPhosphoserine residuesK signalingPoint mutationsSignalingPhosphatidylinositolProteinReticulumRPL36
2021
Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates
Na Z, Luo Y, Cui DS, Khitun A, Smelyansky S, Loria JP, Slavoff SA. Phosphorylation of a Human Microprotein Promotes Dissociation of Biomolecular Condensates. Journal Of The American Chemical Society 2021, 143: 12675-12687. PMID: 34346674, PMCID: PMC8564862, DOI: 10.1021/jacs.1c05386.Peer-Reviewed Original ResearchConceptsMembraneless organellesSmall open reading framesP-body dynamicsLiquid-liquid phase separationOpen reading frameGrowth factor signalingPresence of RNAEvolutionary conservationP-bodiesCellular processesCell divisionReading frameProteogenomic identificationFactor signalingMacromolecular complexesBiomolecular condensatesSecondary structureAmino acidsCell growthMicroproteinsPhosphorylationCell proliferationOrganellesBiophysical processesProliferation
2020
Discovery of cellular substrates of human RNA-decapping enzyme DCP2 using a stapled bicyclic peptide inhibitor
Luo Y, Schofield JA, Na Z, Hann T, Simon MD, Slavoff SA. Discovery of cellular substrates of human RNA-decapping enzyme DCP2 using a stapled bicyclic peptide inhibitor. Cell Chemical Biology 2020, 28: 463-474.e7. PMID: 33357462, PMCID: PMC8052284, DOI: 10.1016/j.chembiol.2020.12.003.Peer-Reviewed Original ResearchConceptsRNA decayEnzyme DCP2P-bodiesDCP2Genetic approachesRNA substratesBicyclic peptide inhibitorsHuman RNAExpression changesCellular substratesPhage display selectionSelective chemical inhibitorsChemical inhibitorsHuman cellsGenetic ablationBicyclic peptide ligandsPeptide inhibitorCP21Display selectionPeptide ligandsHigh affinityRegulomeTranscriptionInhibitorsPowerful toolThe NBDY Microprotein Regulates Cellular RNA Decapping
Na Z, Luo Y, Schofield JA, Smelyansky S, Khitun A, Muthukumar S, Valkov E, Simon MD, Slavoff SA. The NBDY Microprotein Regulates Cellular RNA Decapping. Biochemistry 2020, 59: 4131-4142. PMID: 33059440, PMCID: PMC7682656, DOI: 10.1021/acs.biochem.0c00672.Peer-Reviewed Original ResearchConceptsP-bodiesNonsense-mediated decay factorsKO cellsSmall open reading framesCytoplasmic ribonucleoprotein granulesOpen reading frameSubstrate transcriptsCellular transcriptomeRibonucleoprotein granulesTarget transcriptsRNA stabilityKnockout cellsUTR lengthReading frameGlobal profilingProteogenomic identificationMacromolecular complexesHuman RNACellular RNACytoplasmic RNAGene stabilityAmino acidsCell growthMicroproteinsTranscriptsComparative Proteomic Profiling of Unannotated Microproteins and Alternative Proteins in Human Cell Lines
Cao X, Khitun A, Na Z, Dumitrescu DG, Kubica M, Olatunji E, Slavoff SA. Comparative Proteomic Profiling of Unannotated Microproteins and Alternative Proteins in Human Cell Lines. Journal Of Proteome Research 2020, 19: 3418-3426. PMID: 32449352, PMCID: PMC7429271, DOI: 10.1021/acs.jproteome.0c00254.Peer-Reviewed Original ResearchConceptsRibosome profilingHuman cell linesQuantitative mass spectrometry-based proteomicsCell linesMass spectrometry-based proteomicsLabel-free quantitative proteomicsComplex human proteomeLabel-free comparative proteomicsAlternative open reading framesStress-dependent expressionSpectrometry-based proteomicsTissue-specific expressionOpen reading frameComparative proteomic profilingUnannotated ORFsComparative proteomicsUnannotated proteinsMammalian cellsHuman proteomeQuantitative proteomicsDifferential translationReading frameProteomic profilingHuman leukemia cell linesRegulated expressionGlobal Profiling of Cellular Substrates of Human Dcp2
Luo Y, Schofield J, Simon MD, Slavoff SA. Global Profiling of Cellular Substrates of Human Dcp2. Biochemistry 2020, 59: 4176-4188. PMID: 32365300, PMCID: PMC7641959, DOI: 10.1021/acs.biochem.0c00069.Peer-Reviewed Original ResearchConceptsDecapping enzymeFirst committed stepCellular transcriptsP-bodiesRNA decayCommitted stepHuman transcriptomeMammalian cellsMolecular marksKnockout cellsGlobal profilingConsensus sequenceCellular substratesDCP2Human cellsTranscriptsEnzymeEnzyme substrateCellsDistinct subsetsTranscriptomeAdditive effectEnrichmentRNACytoplasm
2019
Proteomic Detection and Validation of Translated Small Open Reading Frames
Khitun A, Slavoff SA. Proteomic Detection and Validation of Translated Small Open Reading Frames. Current Protocols In Chemical Biology 2019, 11: e77. PMID: 31750990, PMCID: PMC6878975, DOI: 10.1002/cpch.77.Peer-Reviewed Original ResearchConceptsSiRNA-based silencingSmall open reading framesNon-AUG start codonsOpen reading frameStandard proteomic methodsSpecific transcript isoformsCultured human cellsUnique tryptic peptidesGenomic lociShorter proteinTranscript isoformsProtein databaseProteomic methodsNovel regulatorReading frameProteomic detectionStart codonFunctional characterizationMass spectrometry-based detectionComplete annotationSmall proteinsHuman cellsTryptic peptidesProtein extractionSmORFs
2016
A human microprotein that interacts with the mRNA decapping complex
D'Lima NG, Ma J, Winkler L, Chu Q, Loh KH, Corpuz EO, Budnik BA, Lykke-Andersen J, Saghatelian A, Slavoff SA. A human microprotein that interacts with the mRNA decapping complex. Nature Chemical Biology 2016, 13: 174-180. PMID: 27918561, PMCID: PMC5247292, DOI: 10.1038/nchembio.2249.Peer-Reviewed Original Research
2014
A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining*
Slavoff SA, Heo J, Budnik BA, Hanakahi LA, Saghatelian A. A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining*. Journal Of Biological Chemistry 2014, 289: 10950-10957. PMID: 24610814, PMCID: PMC4036235, DOI: 10.1074/jbc.c113.533968.Peer-Reviewed Original ResearchDiscovery of Human sORF-Encoded Polypeptides (SEPs) in Cell Lines and Tissue
Ma J, Ward CC, Jungreis I, Slavoff SA, Schwaid AG, Neveu J, Budnik BA, Kellis M, Saghatelian A. Discovery of Human sORF-Encoded Polypeptides (SEPs) in Cell Lines and Tissue. Journal Of Proteome Research 2014, 13: 1757-1765. PMID: 24490786, PMCID: PMC3993966, DOI: 10.1021/pr401280w.Peer-Reviewed Original ResearchConceptsShort open reading framesNon-AUG start codonsOpen reading frameCell linesHuman genomeMammalian cellsReading frameStart codonAdditional cell linesPolypeptide productsMolecular biologyUbiquitous classK562 cellsGenomeProteomeHuman SEPsPolypeptideHuman tissuesNew SEPCellsCodonDiscoveryBiologyTissueLines
2013
Chemoproteomic Discovery of Cysteine-Containing Human Short Open Reading Frames
Schwaid AG, Shannon DA, Ma J, Slavoff SA, Levin JZ, Weerapana E, Saghatelian A. Chemoproteomic Discovery of Cysteine-Containing Human Short Open Reading Frames. Journal Of The American Chemical Society 2013, 135: 16750-16753. PMID: 24152191, PMCID: PMC3868496, DOI: 10.1021/ja406606j.Peer-Reviewed Original ResearchConceptsShort open reading framesOpen reading frameReading frameProtein-coding genesProtein-coding potentialGene-finding algorithmsAffinity-based approachRibosome profilingNew genesHuman proteomeMass spectrometry technologyEndogenous RNASpectrometry technologyLabeling approachGenesHuman SEPsPotential importanceInvaluable insightsExperimental approachGenomeProteomeDiscoveryRNABiologyPolypeptide
2012
Peptidomic discovery of short open reading frame–encoded peptides in human cells
Slavoff SA, Mitchell AJ, Schwaid AG, Cabili MN, Ma J, Levin JZ, Karger AD, Budnik BA, Rinn JL, Saghatelian A. Peptidomic discovery of short open reading frame–encoded peptides in human cells. Nature Chemical Biology 2012, 9: 59-64. PMID: 23160002, PMCID: PMC3625679, DOI: 10.1038/nchembio.1120.Peer-Reviewed Original ResearchDiscovering ligand-receptor interactions
Slavoff SA, Saghatelian A. Discovering ligand-receptor interactions. Nature Biotechnology 2012, 30: 959-961. PMID: 23051814, DOI: 10.1038/nbt.2373.Peer-Reviewed Original Research
2011
Imaging Protein–Protein Interactions inside Living Cells via Interaction-Dependent Fluorophore Ligation
Slavoff SA, Liu DS, Cohen JD, Ting AY. Imaging Protein–Protein Interactions inside Living Cells via Interaction-Dependent Fluorophore Ligation. Journal Of The American Chemical Society 2011, 133: 19769-19776. PMID: 22098454, PMCID: PMC3547671, DOI: 10.1021/ja206435e.Peer-Reviewed Original Research