Modulation of Transcription Factor Activity by Mono-Ubiquitin

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dc.contributor.advisorKodadek, Thomas J.en
dc.creatorArcher, Chase Tanneren
dc.date.accessioned2010-07-12T17:32:07Z
dc.date.available2010-07-12T17:32:07Z
dc.date.issued2008-09-12
dc.description.abstractThe Ubiquitin-Proteasome Pathway plays both proteolytic and non-proteolytic roles in the regulation of transcription. We recently reported that the ATPases of the 26S proteasome can destabilize activator-DNA complexes in a non-proteolytic manner that requires direct interactions between the Rpt4 and 6 subunits with the activation domain of the activator. Remarkably, mono-ubiquitylation of the activator blocks this repressive activity. In this study, we probe the mechanism of this protective effect. Using novel label transfer and chemical cross-linking techniques, we show that ubiquitin contacts the ATPase complex directly, apparently via Rpn1 and/or Rpt1, and that this interaction results in the dissociation of the activation domain-ATPase complex via an allosteric process. We also provide in vivo evidence demonstrating the importance of monoubiquitylation in inhibition of activator-DNA destabilization. A model is proposed in which activator mono-ubiquitylation serves to limit the lifetime of the activator-ATPase complex interaction and thus the ability of the ATPases to unfold the activator and dissociate the protein-DNA complex.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc297228246
dc.identifier.urihttps://hdl.handle.net/2152.5/310
dc.language.isoenen
dc.subjectUbiquitinen
dc.subjectProteolysisen
dc.subjectTranscription Factorsen
dc.titleModulation of Transcription Factor Activity by Mono-Ubiquitinen
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2009-09-12
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineBiological Chemistryen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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