Abstract
RASSF7 is part of a novel group of proteins, the N-terminal RAS association domain family, which has been recently described as a distinct and evolutionary conserved group of Ras association domain containing members. The biological function of these members is still unclear, but at least some of these proteins may play a role in oncogenesis.The aim of this project was to understand the role of mammalian RASSF7, which is up-regulated in a variety of cancers but whose direct contribution to tumour progression has still to be proved. RASSF7 was found to be an integral centrosomal component which is broadly expressed during mouse embryogenesis and in adult tissues. It is also expressed in every human cell line tested so far. Knockdown of RASSF7 severely impairs cell growth in H1792 and HeLa cells and causes major mitotic defects in HeLa cells. In fact, RASSF7 depletion compromises spindle formation and choromosomal congression in these cells. Furthermore Aurora B, which plays a fundamental role in the maintenance of genome integrity, is not activated in the knockdowns. Finally microtubule re-growth assays show that RASSF7 is a key regulator of microtubule dynamics.
Overall, the data presented in this thesis provide the first functional analysis of human RASSF7, indicating that this protein has a key role in regulating microtubules during mitosis, and suggest that the misregulation of RASSF7 in cancer cells might promote genomic instability.
| Date of Award | 1 Feb 2011 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Andrew Chalmers (Supervisor) & Andrew Ward (Supervisor) |
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