Regulation of C-RAF stability by the RanBPM/CTLH complex

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.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Biochemistry

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2017

Author dc:creator

• McTavish, Christina J

Advisor dc:contributor.advisor

• Schild-Poulter, Caroline

• RanBPM
• C-RAF
• ERK1/2 pathway
• CTLH complex
• protein stability
• RMND5A

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/27682

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/27682