Regulation der Proteindegradation durch kanonische Wnt Signalgebung; Erforschung von Kreuzungspunkten verschiedener Signalkaskaden und ihre Auswirkung auf die Embryonalentwicklung und Pathogenese im Menschen durch Nutzung des Modellorganismus Xenopus laev

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Integration of diverse signaling pathways can potentially explain how the embryonic body plan is regulated and how human diseases are caused. The major signaling pathways involved are the bone morphogenic protein (Bmp), the Wnt, the MAPK and the Hedgehog networks. The duration of Bmp signals establishing the axis of early Xenopus embryos have been recently discovered to be increased by Wnt signaling at the stage of the transcription factor Smad1. Unpublished findings in the host lab indicate that Wnt signals lead to a translocation of cellular GSK3 to the pericentrosomal region, a proteolytic center of the cell. Furthermore, canonical Wnt signals in cultured cells and Drosophila embryos increase the level of total polyubiquitinylated proteins. The working hypothesis is that Wnt signaling is a general inhibitor of protein catabolism. I propose: I) to identify which proteins are blocked for degradation by Wnt signaling using proteomic analyses and His-tagged ubiquitin, II) to study the modulation of the proteasome system by Wnt signals in Xenopus embryo, III) to investigate the impact of Wnt signaling on asymmetrical protein segregation and cell division. From these studies I hope to contribute to how signaling cascades influence their functions in human disease or embryogenesis.