Doktorské studium

Studijní obor Biomolekulární chemie

Název práce: Axin scaffoldosome: development of specific inhibitors of individual protein-protein interactions


Předběžné zadání:
Final Description Axin is a multi-domain tumor suppressor protein that functions as a scaffold for at least four different signaling pathways: the Wnt, the transforming growth factor b (TGF-b), the c-Jun NH2-terminal/stress-activated protein kinase (JNK), and the p53. These pathways are involved in regulation of variety of fundamental processes such as cell proliferation, differentiation, apoptosis, or morphogenesis, for example. Dysregulation of these pathways has been implicated in a large variety of cancers. Given the lack of detailed topological and chronological information on binding events between Axin and signaling cascade-specific proteins, it remain unresolved how the recruitment and positioning of more than 40 different Axin binding partners are coordinated to pass signal along specific signaling cascade. Current understanding of the function of individual signaling cascades is based mostly on overexpression studies and one of the main reasons, why even after decades of intensive research we do not understand how the signal via Axin is redirected and transduced in different directions, is the lack of basic structural information and definition of direct binding surfaces with other proteins. In the proposed project we aim to address this issues using unique combination of various cell biological, biochemical and biophysical approaches. General aim of the proposed project is to dissect the Axin interactosome to enable functionally characterize the role of binding of individual proteins to Axin for signal transduction and to allow systematic search for specific inhibitors of individual protein-protein interactions that could serve as tools for therapeutic intervention of aberrant signaling.
vedoucí:Mgr. Lukáš Trantírek, Ph.D. učo 8725

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