Abstract
RASSF7 protein localises to the centrosome and plays a key role in mitosis. Its expression is also increased in a range of tumour types. However, little is known about the molecular basis of RASSF7’s function and it is not clear if it acts as an oncogene in the cancers where its levels are elevated. This thesis carries out the first analysis of the domains of rassf7, focusing on which of them are responsible for its localisation.Constructs were generated to allow the expression of a series of truncated versions of rassf7 and the localisation of these proteins were analysed. This was carried out in Xenopus embryos and my data shows that the coiled-coil domain of rassf7 is required and sufficient to direct its centrosomal localisation. Surprisingly, removal of the extreme C-terminus of the protein caused rassf7 to accumulate at the centrosome and drive centrosome and mitotic defects, and ultimately cell death. Interestingly, analysis of a database of tumour sequences identified a mutation in RASSF7, which would cause a similar C-terminal truncation of the protein. Based on my data, this truncated protein might drive centrosomal defects and we propose the hypothesis that truncated RASSF7 could act as an oncogene in a small subset of tumours with such mutations. Finally, studies in Xenopus showed the first evidence that RASSF7 can localise at the tight junctions. The coiled-coil domain was found to be required for driving the tight junctional localisation of rassf7. This data suggests a new function for rassf7 at the junctions that will be an interesting avenue for future work.
| Date of Award | 17 Jun 2015 |
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| Original language | English |
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| Supervisor | Andrew Chalmers (Supervisor) & Paul Whitley (Supervisor) |