The project is carried out in close collaboration with Dr. Mireia Duñach (Universitat Autònoma de Barcelona). Our group has focused to the study of E-caderin-associated proteins, such as β-catenin and p120-catenin, and their dual role as regulators of transcription and modulators of E-cadherin function. In recent years, our work has focussed on p120-catenin which, in addition to binding with and stabilise E-cadherin, has other functions as it controls the activity of the Rho family of GTPases and the Kaiso transcription factor. Our results have indicated that p120-catenin plays an additional role in the Wnt signaling, a pathway that induces β-catenin transcriptional activity. p120-catenin/E-cadherin complex is bound to the LRP5/6 Wnt co-receptor and is necessary for the very early responses to Wnt, such as the activation of CK1e. Furthermore, the separation of the p120-catenin from the complex, which takes place later, is required for the full stabilisation of β-catenin and also p120-catenin to facilitate the transit of β-catenin to the nucleus and eliminate the inhibition caused by Kaiso on the transcriptional activity of the β-catenin/TCF-4 complex. A current model of our vision of this pathway is found in Figure 1.
The three latest publications on this topic are:
Figure 1: Fast and late regulation of the activity of GSK3 on β-catenin and the stability of this protein. For more information, Vinyoles et al (2014).