The conserved Metazoan protein β-catenin has important functions in both Wnt signalling and Cadherin-mediated adhesion. Tight regulation of β-catenin levels and location within cells is vital for the correct control of homeostasis, differentiation, morphogenesis and cell migration in developing and adult Metazoa. Misregulation of β- catenin leads to cells with altered proliferative and migratory properties and can lead to cancer. The Metazoan proteins BCL9 and Pygopus are important for the regulation of β- catenin and show different requirements in different organisms. β-catenin binds to BCL9, which binds to Pygopus. These interactions are thought to be involved in activation of Wnt signalling-dependent transcription, localisation of β-catenin and cross-talk between Wnt signalling and Cadherin-mediated adhesion. This thesis describes experiments using the frog Xenopus laevis to characterise the activities of carnosate, a small molecule inhibitor of the β-catenin-BCL9 interaction, and to assess its potential value as a drug for cancer therapy. More generally this thesis describes experiments undertaken towards a better understanding of how β-catenin links Wnt signalling and Cadherin-mediated adhesion and what role BCL9 and Pygopus play in this regard.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:531887 |
| Date | January 2010 |
| Creators | Monaghan, John |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158564 |
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