dc.contributor.author | McPhee, Michael Jordan | |
dc.date.accessioned | 2019-11-28T16:49:59Z | |
dc.date.available | 2019-11-28T16:49:59Z | |
dc.date.issued | 2019-11-28T16:49:59Z | |
dc.identifier.uri | http://hdl.handle.net/10222/76711 | |
dc.description.abstract | CTP:phosphocholine cytidylyltransferase alpha (CCTα) catalyzes the rate-limiting step of PC synthesis via the CDP-choline pathway. This study investigated CCTα regulation by phosphorylation using phospho-specific antibodies raised against p-S315/S319 and
p-Y359/S362. Both antibodies detected endogenous CCTα and CCTβ in human cells, but Y359/S362 did not detect overexpressed CCTα or CCTβ. Oleate/BSA treatments induced dephosphorylation of CCTα at S315/S319 but not Y359/S362 in multiple human and rat cell lines. This correlated with translocation of CCTα to the inner nuclear membrane (INM) and decreased nuclear p-S315/S319 signal. Choline depletion of H-ras-transformed rat intestinal epithelial cells (IEC-ras) also induced dephosphorylation of S315/S319. This study is the first to use phospho-specific antibodies for CCTα to monitor dephosphorylation in response to enzyme activation. The mechanism of CCTα promoting IEC-ras survival was also investigated, suggesting that autophagy, PERK-eIF2α-ATF4-CHOP, and Keap1-Nrf2 pathways are not induced by inhibiting PC synthesis in IEC-ras. How CCTα promotes malignancy remains unknown. | en_US |
dc.language.iso | en | en_US |
dc.subject | phosphatidylcholine | en_US |
dc.subject | CTP:phosphocholine cytidylyltransferase alpha | en_US |
dc.subject | phosphorylation | en_US |
dc.subject | enzyme regulation | en_US |
dc.subject | intestinal epithelial cells | en_US |
dc.subject | ras-transformation | en_US |
dc.subject | phospho-regulation | en_US |
dc.title | AN INVESTIGATION OF PHOSPHO-REGULATION AND THE ROLE CTP:PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE α IN PROMOTING RAS-INDUCED MALIGNANT TRANSFORMATION OF INTESTINAL EPITHELIAL CELLS | en_US |
dc.date.defence | 2018-08-14 | |
dc.contributor.department | Department of Biochemistry & Molecular Biology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | n/a | en_US |
dc.contributor.graduate-coordinator | Jan Rainey | en_US |
dc.contributor.thesis-reader | Roy Duncan | en_US |
dc.contributor.thesis-reader | Aarnoud C. van der Spoel | en_US |
dc.contributor.thesis-reader | Kirill V. Rosen | en_US |
dc.contributor.thesis-supervisor | Neale D. Ridgway | en_US |
dc.contributor.ethics-approval | Not Applicable | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |