Regulation of tail-anchored ubiquitin conjugating enzymes that are localised to the endoplasmic reticulum

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dc.check.date10000-01-01
dc.check.embargoformatBoth hard copy thesis and e-thesisen
dc.check.entireThesisEntire Thesis Restricted
dc.check.infoIndefiniteen
dc.check.opt-outYesen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorFleming, John V (Eoin)en
dc.contributor.authorLam, Shuet-Yin
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2016-09-28T08:31:27Z
dc.date.issued2016
dc.date.submitted2016
dc.description.abstractThe vast majority of secreted and membrane proteins are translated and folded at the endoplasmic reticulum (ER), where a sophisticated quality control mechanism ensures that only correctly folded proteins exit the ER and traffic to their final destinations. On the other hand, proteins that persistently misfold are eliminated through a process known as ER associated degradation (ERAD). This involves retrotranslocation of the misfolded protein through the ER membrane, and ubiquitination in advance of degradation by cytosolic proteasomes. The process of ERAD is best described in yeast where ubiquitin conjugating enzymes Ubc6p and Ubc7p function with a limited number of E3 ubiquitin ligases to ubiquitinate misfolded proteins. Interestingly, although the mechanistic principles of ERAD have been conserved through evolution, there is increasing evidence that homologues of the yeast enzymes have gained divergent roles and novel regulatory functions in higher eukaryotes, meaning that the process in humans is more complex and involves a larger repertoire of participating proteins. Two homologues of Ubc6p have been described in humans, and have been named as Ubc6 (UBE2J2) and Ubc6e (UBE2J1). However, little work has been done on these enzymes and thus our main objective of this study was to progress the functional characterisation of these ERAD E2 conjugating enzymes. Our studies included a detailed analysis of conditions whereby these proteins are stabilised and degraded. We’ve also explored the different molecular signalling pathways that induced changes on their steady state protein levels. Furthermore, Ubc6e has a phosphorylatable serine residue at position 184. Thus, our studies also involved delineating the signalling kinases that phosphorylate Ubc6e and examining its function in ERAD. Our studies confirm that the E2 Ubc enzymes are regulated posttranslationally and may have important implications in the regulation of ERAD.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLam, S-Y. 2016. Regulation of tail-anchored ubiquitin conjugating enzymes that are localised to the endoplasmic reticulum. PhD Thesis, University College Cork.en
dc.identifier.urihttps://hdl.handle.net/10468/3123
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2016, Shuet-Yin Lam.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectMitogen-activated protein kinaseen
dc.subjectER stressen
dc.subjectUnfolded protein responseen
dc.subjectEndoplasmic reticulum associated degradationen
dc.subjectUbiquitin conjugating enzymeen
dc.thesis.opt-outtrue
dc.titleRegulation of tail-anchored ubiquitin conjugating enzymes that are localised to the endoplasmic reticulumen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoral Degree (Structured)en
dc.type.qualificationnamePhD Scholars Programme in Cancer Biologyen
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