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dc.contributor.authorRekab, Aishaen
dc.date.accessioned2019-07-26T21:05:21Z
dc.date.available2019-07-26T21:05:21Z
dc.identifier.urihttp://hdl.handle.net/1974/26439
dc.description.abstractPheochromocytomas (PCC) are highly heritable neoplasms of the adrenal gland, carrying germline mutations in approximately 40% of cases. PCC susceptibility genes have been subdivided into two clusters: hypoxia-related genes, and kinase-signalling genes, which include the RET receptor tyrosine kinase and Transmembrane protein 127 (TMEM127). RET is an established oncogene that causes aberrant activation of PI3K-AKT and MAPK-ERK signalling in various neuroendocrine cancers. Both wildtype (WT) RET and TMEM127 localize to multiple subcellular compartments including the Golgi apparatus, early endosomes and lysosomes. TMEM127 has been suggested to play a role in endosomal transition, however the function of TMEM127 has yet to be elucidated. In this study we evaluated the relationship between the RET receptor tyrosine kinase and TMEM127. We have identified a potential role of TMEM127 in RET protein maturation and transport to the plasma membrane. We were able to rule out a relationship between RET and TMEM127 at the transcriptional level, and at the level of RET protein folding. We also observed a relationship with TMEM127 mutants and total RET protein expression, which may correlate with TMEM127 mutant diffuse localization. Overall, the findings presented here suggest a novel interplay between RET and TMEM127 that may lead to a more thorough understanding of aberrant protein trafficking in human neoplasms and contribute to our overall understanding of the molecular mechanisms of PCC susceptibility genes.en
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectRETen
dc.subjectTMEM127en
dc.subjectPheochromocytomaen
dc.subjectIntracellular traffickingen
dc.titleEvaluating the relationship between the RET receptor tyrosine kinase and TMEM127en
dc.typethesisen
dc.description.degreeM.Sc.en
dc.contributor.supervisorMulligan, Loisen
dc.contributor.departmentPathology and Molecular Medicineen
dc.embargo.termsWe would like to restrict this thesis as the Mulligan lab is continuing work on this project, with plans to publish this work.en
dc.embargo.liftdate2024-07-26T09:39:43Z
dc.embargo.liftdate2024-07-26T19:26:33Z
dc.degree.grantorQueen's University at Kingstonen


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