2021
The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress
Phoomak C, Cui W, Hayman TJ, Yu SH, Zhao P, Wells L, Steet R, Contessa JN. The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress. Science Advances 2021, 7: eabc6364. PMID: 33523898, PMCID: PMC7810369, DOI: 10.1126/sciadv.abc6364.Peer-Reviewed Original ResearchTranslocon-associated proteinN-glycosylationER stressER glycoprotein quality controlTranslocon-associated protein complexEndoplasmic reticulum (ER) homeostasisAberrant N-glycosylationGlycoprotein quality controlER chaperone BiPFluorescence-based strategyProtein complexesPosttranslational modificationsChaperone BiPTRAP complexGlycosylation defectsConditions of stressRegulatory roleTranscriptional signatureIndividual cellsDownstream ERProtein levelsSubunitsSSR3GlycosylationCells
2019
Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing
Klaver E, Zhao P, May M, Flanagan-Steet H, Freeze HH, Gilmore R, Wells L, Contessa J, Steet R. Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing. Disease Models & Mechanisms 2019, 12: dmm039602. PMID: 31101650, PMCID: PMC6602306, DOI: 10.1242/dmm.039602.Peer-Reviewed Original ResearchConceptsNull cellsReceptor processingEndoplasmic reticulum localizationGlycan site occupancyInsulin-like growth factor 1 receptorReceptor tyrosine kinasesGrowth factor 1 receptorFactor 1 receptorCell surface glycoproteinMutant cellsNGI-1Catalytic subunitReceptor kinaseGlycosylation statusReduced abundanceTyrosine kinaseGlycan occupancyTyrosine receptor kinaseSurface localizationInsulin receptorAbnormal glycosylationProteolytic processingFunctional consequencesCell surfaceGlycosylation
2018
Editing N-Glycan Site Occupancy with Small-Molecule Oligosaccharyltransferase Inhibitors
Rinis N, Golden JE, Marceau CD, Carette JE, Van Zandt MC, Gilmore R, Contessa JN. Editing N-Glycan Site Occupancy with Small-Molecule Oligosaccharyltransferase Inhibitors. Cell Chemical Biology 2018, 25: 1231-1241.e4. PMID: 30078634, PMCID: PMC6337728, DOI: 10.1016/j.chembiol.2018.07.005.Peer-Reviewed Original ResearchConceptsNGI-1Cellular unfolded protein responseMultisubunit enzyme complexN-glycan site occupancyUnfolded protein responseSubset of glycoproteinsSubunit-specific inhibitorsSecretory pathwayCatalytic subunitProtein responseEnzyme complexTarget proteinsOligosaccharyltransferasePharmacologic inhibitionGlycosylationProteinCell modelBiological effectsInhibitorsStructure-activity relationshipsSTT3BSTT3APharmacological approachesSubunitsSite occupancy