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Degree

Master of Science

Program

Biochemistry

Supervisor

Schild-Poulter, Caroline

Abstract

RanBPM is a highly conserved protein that has been shown to impact numerous cellular processes including migration, proliferation, and apoptosis. RanBPM exists in a multi-protein complex called the CTLH complex, which functions as an E3 ubiquitin ligase. A putative member of the CTLH complex, WDR26, has been implicated in the Wnt pathway through regulating β-catenin protein levels. This study investigated whether β-catenin regulation is performed by the CTLH complex. WDR26 was confirmed as part of the CTLH complex, and this complex is interacting with Axin1. CTLH members RanBPM and RMND5A both regulate beta-catenin levels in a proteasome dependent manner. Additionally, this regulation affected downstream expression of β-catenin target genes. Together these results have revealed a potential target of the CTLH complex and suggests a novel mechanism that regulates Wnt signalling. This study has revealed new insights into the CTLH complex functioning as a novel tumour suppressor.

Summary for Lay Audience

RanBPM is a highly conserved protein that has been shown to impact numerous cellular processes including migration, proliferation, and apoptosis. RanBPM exists in a multi-protein complex called the CTLH complex, which functions as an E3 ubiquitin ligase. A putative member of the CTLH complex, WDR26, has been implicated in the Wnt pathway through regulating β-catenin protein levels. This study investigated whether β-catenin regulation is performed by the CTLH complex. WDR26 was confirmed as part of the CTLH complex, and this complex is interacting with Axin1. CTLH members RanBPM and RMND5A both regulate beta-catenin levels in a proteasome dependent manner. Additionally, this regulation affected downstream expression of β-catenin target genes. Together these results have revealed a potential target of the CTLH complex and suggests a novel mechanism that regulates Wnt signalling. This study has revealed new insights into the CTLH complex functioning as a novel tumour suppressor.

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