Role of eEF1A in the Nuclear Export of the VHL Tumour Suppressor Protein

Abstract

The ability of proteins to engage in nuclear-cytoplasmic shuttling is required for their proper function. The nuclear export of the von Hippel Lindau (VHL) tumour suppressor protein is necessary for the proteasomal degradation of the hypoxia inducible factor alpha (HIFα). Studies have identified that the nuclear export of VHL and other proteins encoding a Transcription-Dependent Nuclear Export Motif (TD-NEM) is independent of the classical CRM1 nuclear export pathway but requires ongoing transcription. Furthermore, the eukaryotic elongation factor 1 alpha (eEF1A) was identified as a mandatory component of the TD-NEM-mediated nuclear export machinery. In this study, we have uncovered the ability of eEF1A to mediate the nuclear export of proteins by accessing the nuclear compartment in its inactive, GDP-bound form. Although previously thought of as a strictly cytoplasmic protein, work conducted in this thesis has shown that eEF1A is a nuclear-cytoplasmic shuttling protein and this ability is required for the effective export of proteins encoding a TD-NEM.