Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor

Caroline Schild-Poulter

Abstract

RanBPM/RanBP9 is a multi-domain nucleocytoplasmic protein which has been linked to numerous cellular processes including cell adhesion, migration, transcription and apoptosis. Although RanBPM is a member of the mammalian CTLH complex, the counterpart of a conserved yeast E3 ubiquitin ligase complex, its exact function remains unknown. Previous work in our laboratory has shown that RanBPM inhibits the ERK pathway by interacting with the kinase c-Raf and downregulating c-Raf levels. Here, we show that the N-terminus, LisH/CTLH and CRA domains of RanBPM are required for downregulation of c-Raf and that RanBPM interacts directly with c-Raf through its CRA domain. We also provide evidence that MAEA, another CTLH complex member, associates with c-Raf. Therefore, we propose a mechanism by which RanBPM downregulates c-Raf in a CTLH complex-dependent manner. This work contributes to our knowledge of the function of RanBPM and clarifies the relationship between RanBPM and c-Raf, two important proteins in oncogenesis.

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