Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian hippo signalling pathway
Abstract
The Salvador/Warts/Hippo (Hippo) pathway defines a novel signalling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer development in mammals. The Hippo pathway was initially utilised in D. melanogaster, where the Expanded protein acts in the Hippo signalling cascade to control organ size. Willin is the proposed
human orthologue of Expanded and the aim of this thesis is to investigate
whether willin can activate the mammalian Hippo signalling pathway. Ectopic willin expression causes an increase in phosphorylation of the core Hippo signalling pathway components MST1/2, LATS1 and YAP, an effect which can be antagonised by ezrin. In MCF10A cells, willin over-expression
antagonises a YAP-induced epithelial-to-mesenchymal transition via the N-
terminal FERM (Four-point-one Ezrin Radixin Moesin) domain of willin. Preliminary results show that willin is expressed within the sciatic nerve of rat and mice, and within the neuromast cells in the zebrafish; suggesting that willin and the Hippo pathway may play a vital role in the developmental regulation within the peripheral nervous system. To conclude, willin influences
Hippo signalling activity by activating the core Hippo pathway kinase cassette
in mammalian cells.
Type
Thesis, PhD Doctor of Philosophy
Rights
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