Elucidating the regulation and dynamics of [beta]-O-N-acetyl-D-glucosamine (O-GlcNAc) during signal transduction

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dc.contributor.advisorMagnus, Philip D.en
dc.contributor.advisorMahal, Lara K.en
dc.contributor.committeeMemberIverson, Brenten
dc.contributor.committeeMemberRoux, Stanleyen
dc.contributor.committeeMemberAppling, Deanen
dc.contributor.committeeMemberLiu, Hung-Wenen
dc.creatorCarrillo Millán, Luz Damarisen
dc.date.accessioned2011-01-26T17:05:40Zen
dc.date.accessioned2011-01-26T17:05:55Zen
dc.date.accessioned2017-05-11T22:21:07Z
dc.date.available2011-01-26T17:05:40Zen
dc.date.available2011-01-26T17:05:55Zen
dc.date.available2017-05-11T22:21:07Z
dc.date.issued2010-05en
dc.date.submittedMay 2010en
dc.date.updated2011-01-26T17:05:55Zen
dc.descriptiontexten
dc.description.abstractThe ability of cells to respond to their microenvironment is controlled by a complex communication system. Cell signaling utilizes a series of post-translational events to regulate and coordinate cellular activities. Although phosphorylation is thought to be the key regulator of these events, recent findings implicate the O-GlcNAc modification as an additional control mechanism. Modulation of signal transduction requires compartmentalization of the kinases and phosphatases. Based on the evidence of subcellular localization of OGT isoforms, the diversity of O-GlcNAcylated proteins upon stimulation, and its role during insulin signaling, it can be hypothesized that O-GlcNAc is involved and regulates signal transduction in a compartmentalized manner. To investigate the spatio-temporal dynamics of O-GlcNAc in cell signaling, we have generated a series of genetically encoded O-GlcNAc reporters based on fluorescence resonance energy transfer (FRET). These reporters and localized variants have allowed compartment specific visualization of O-GlcNAc activity in the nucleus, cytoplasm and plasma membrane. Herein we describe these reporters and their use to examine O-GlcNAc dynamics in signaling using serum stimulation and environmentally relevant concentrations of arsenite. Acute exposure to arsenite through drinking water has become an environmental health concern worldwide. Our results imply a complex regulation of O-GlcNAc on a fast timescale that is tied to more canonical kinase pathways.en
dc.description.departmentChemistry and Biochemistryen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2010-05-1405en
dc.language.isoengen
dc.subjectO-GlcNAcen
dc.subjectFRET sensoren
dc.subjectCell signalingen
dc.subjectNuclear proteinsen
dc.subjectCytoplasmic proteinsen
dc.subjectArseniteen
dc.titleElucidating the regulation and dynamics of [beta]-O-N-acetyl-D-glucosamine (O-GlcNAc) during signal transductionen
dc.type.genrethesisen

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