Role of SCF-type ubiquitin ligases in NF-κB driven lymphomagenesis
Prof. Dr. med. Florian Bassermann
Technical University of Munich
School of Medicine
Department of Hematology and Oncology(link is external)
TranslaTUM(link is external)
Project Summary
Activation of NF-κB is strongly regulated by signaling cascades that depend on protein phosphorylation and degradative and non-degradative functions of the ubiquitin system. We identified the orphan F-Box protein FBXO21 as a prime candidate for the long-sought p50 ubiquitin ligase, and found overexpression of FBXO21 in human B cell malignancies. This project will mechanistically dissect the FBXO21-p50 axis in the context of lymphoma development and maintenance. In parallel, we will explore the overall role of F-box family ubiquitin ligases and their counter players, the deubiquitylases, in NF-κB control and cancer-linked aberrations thereof using functional genetic screens and proteomic approaches.
Immunomodulatory drugs, including the Contergan derivatives lenalidomide and pomalidomide, have significantly improved the therapy of hematologic malignancies such as multiple myeloma. Researchers at the Technical University of Munich (TUM) have now further decoded the mode of action in this class of medications.
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