The regulation of protein degradation at the endoplasmic reticulum

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dc.availability.bitstreamembargoed
dc.check.date2032-05-30
dc.contributor.advisorFleming, John V (Eoin)en
dc.contributor.authorO'Nualláin, Fearghal
dc.date.accessioned2022-01-31T13:31:06Z
dc.date.available2022-01-31T13:31:06Z
dc.date.issued2021-06-28
dc.date.submitted2021-06-28
dc.description.abstractThe majority of membrane and secretory protein synthesis in the cell occurs in the endoplasmic reticulum (ER) where proteins reach their native energy stable folded state and are subsequently transported to their functional location. Aberrations in this process whereby a protein cannot reach its intended location or cannot fold correctly often result in accumulation of that protein in the ER lumen. This is toxic to the cell and ER stress is induced in an effort to remove the misbehaving protein to avoid cellular stress and damage. Chaperones can be recruited to assist protein folding but if this is unsuccessful then the protein is marked for degradation via endoplasmic reticulum associated degradation (ERAD). Ubc6 (UBE2J2 in humans) is an E2 ubiquitin conjugating enzyme which catalyses the attachment of ubiquitin to target proteins which marks them for degradation. However, the specific set of substrates which Ubc6 acts upon and the mechanism for its regulation is yet to be understood. In this study, we construct a protein-protein interaction network (PPIN) of Ubc6 to better understand where this protein fits into its environment and to help elucidate what substrates it mediates degradation for. Here, we demonstrate how Ubc6 has the ability to mediate degradation for both a plasma membrane resident protein E-cadherin and also an ER trapped protein HFE C282 (HFE-M). We also show the increased expression of Ubc6 by MAPK signalling through phorbol-12-myristate 13-acetate (PMA) incubation and constitutive BRaf signalling (V600E). Whether this increased expression results in higher Ubc6 stability and/or increased substrate degradation remains to be seen.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Nualláin, F. 2021. The regulation of protein degradation at the endoplasmic reticulum. MSc Thesis, University College Cork.en
dc.identifier.endpage68en
dc.identifier.urihttps://hdl.handle.net/10468/12507
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2021, Fearghal O'Nuallain.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectERADen
dc.subjectUbc6en
dc.subjectBRAF V600Een
dc.subjectUBE2J2en
dc.subjectUbiquitinen
dc.subjectE-cadherinen
dc.subjectHFE C282Yen
dc.subjectProtein degradationen
dc.titleThe regulation of protein degradation at the endoplasmic reticulumen
dc.typeMasters thesis (Research)en
dc.type.qualificationlevelMastersen
dc.type.qualificationnameMSc - Master of Scienceen
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