{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/27682"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/27682","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Regulation of C-RAF stability by the RanBPM/CTLH complex","abstract":"RanBPM is an evolutionarily conserved multi-domain protein that has been implicated in the regulation of several cellular process, including protein stability, cell migration, gene transcription, and apoptosis. RanBPM is identified as a key member of the CTLH complex, an orthologous complex to a yeast E3 ubiquitin ligase complex, the exact function of which remains unknown. Previously, our laboratory identified RanBPM as an inhibitor of the ERK1/2 pathway through the modulation of C-RAF protein levels. This study shows that RanBPM-mediated degradation of C-RAF occurs through the proteasome and the entire CRA domain of RanBPM is necessary for direct interaction with C-RAF and for effective downregulation of C-RAF in human cells. Finally, the CTLH complex member RMND5A regulates endogenous C-RAF protein levels further implicating the CTLH complex in RanBPM-mediated regulation of C-RAF stability. This study provides further insight into the function of RanBPM and the CTLH complex, and their regulation of C-RAF.","abstract_html":"RanBPM is an evolutionarily conserved multi-domain protein that has been implicated in the regulation of several cellular process, including protein stability, cell migration, gene transcription, and apoptosis. RanBPM is identified as a key member of the CTLH complex, an orthologous complex to a yeast E3 ubiquitin ligase complex, the exact function of which remains unknown. Previously, our laboratory identified RanBPM as an inhibitor of the ERK1/2 pathway through the modulation of C-RAF protein levels. This study shows that RanBPM-mediated degradation of C-RAF occurs through the proteasome and the entire CRA domain of RanBPM is necessary for direct interaction with C-RAF and for effective downregulation of C-RAF in human cells. Finally, the CTLH complex member RMND5A regulates endogenous C-RAF protein levels further implicating the CTLH complex in RanBPM-mediated regulation of C-RAF stability. This study provides further insight into the function of RanBPM and the CTLH complex, and their regulation of C-RAF.","abstract_has_math":false,"creators":["McTavish, Christina J"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Schild-Poulter, Caroline"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-09-25","date_published":"2017-09-25","updated_at":"2026-07-27T21:56:14Z","subjects":["RanBPM","C-RAF","ERK1/2 pathway","CTLH complex","protein stability","RMND5A"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/27682","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Schild-Poulter, Caroline"]},{"key":"dc:creator","label":"Author","values":["McTavish, Christina J"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T15:31:39Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T15:31:39Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-09-25"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["RanBPM","C-RAF","ERK1/2 pathway","CTLH complex","protein stability","RMND5A"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/27682"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["RanBPM is an evolutionarily conserved multi-domain protein that has been implicated in the regulation of several cellular process, including protein stability, cell migration, gene transcription, and apoptosis. RanBPM is identified as a key member of the CTLH complex, an orthologous complex to a yeast E3 ubiquitin ligase complex, the exact function of which remains unknown. Previously, our laboratory identified RanBPM as an inhibitor of the ERK1/2 pathway through the modulation of C-RAF protein levels. This study shows that RanBPM-mediated degradation of C-RAF occurs through the proteasome and the entire CRA domain of RanBPM is necessary for direct interaction with C-RAF and for effective downregulation of C-RAF in human cells. Finally, the CTLH complex member RMND5A regulates endogenous C-RAF protein levels further implicating the CTLH complex in RanBPM-mediated regulation of C-RAF stability. This study provides further insight into the function of RanBPM and the CTLH complex, and their regulation of C-RAF."]},{"key":"dc:title","label":"Title","values":["Regulation of C-RAF stability by the RanBPM/CTLH complex"]}]}],"canonical_facts":{"dc:contributor.advisor":["Schild-Poulter, Caroline"],"dc:creator":["McTavish, Christina J"],"dc:date.accessioned":["2025-07-10T15:31:39Z"],"dc:date.available":["2025-07-10T15:31:39Z"],"dc:date.issued":["2017-09-25"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["RanBPM is an evolutionarily conserved multi-domain protein that has been implicated in the regulation of several cellular process, including protein stability, cell migration, gene transcription, and apoptosis. RanBPM is identified as a key member of the CTLH complex, an orthologous complex to a yeast E3 ubiquitin ligase complex, the exact function of which remains unknown. Previously, our laboratory identified RanBPM as an inhibitor of the ERK1/2 pathway through the modulation of C-RAF protein levels. This study shows that RanBPM-mediated degradation of C-RAF occurs through the proteasome and the entire CRA domain of RanBPM is necessary for direct interaction with C-RAF and for effective downregulation of C-RAF in human cells. Finally, the CTLH complex member RMND5A regulates endogenous C-RAF protein levels further implicating the CTLH complex in RanBPM-mediated regulation of C-RAF stability. This study provides further insight into the function of RanBPM and the CTLH complex, and their regulation of C-RAF."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/27682"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["RanBPM","C-RAF","ERK1/2 pathway","CTLH complex","protein stability","RMND5A"],"dc:title":["Regulation of C-RAF stability by the RanBPM/CTLH complex"],"dc:type":["thesis"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:14Z"}