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Projekt
Functions of regulatory ubiquitin and ubiquitin-like modifications for NF-kB signalling in T cells
Antragsteller
Professor Dr. Daniel Krappmann, Ph.D.
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2008 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 71411373
Assembly and disassembly of ubiquitin chains to cellular target proteins is involved in the regulation of many steps in T cell activation. We could previously show that K63-linked ubiquitination of Malt1 promotes the recruitment of IB kinases (IKKs) to the high molecular weight Carma1-Bcl10-Malt1 (CBM) complex, which is a key regulator of T cells activation. We have discovered that TRAF6- catalyzed ubiquitination and A20-mediated deubiquitination of Malt1 balances IKK/NF-B signaling in T cells. In addition, association of Malt1 with the COP9 signalosome – a cellular deneddylating complex – is required for optimal T cell activation and Malt1 is also prone to NEDD8 modifications. Within this project, we will investigate the mechanisms and cellular consequences of Malt1 neddylation. Specifically, we will address the question whether NEDD8 and ubiquitin modifications in Malt1 serve opposing functions that together help to coordinate T cell responses. Further, we will perform a siRNA screen to identify novel deubiquitinating enzymes (DUBs) that are involved in T cell activation. The aim is to obtain a comprehensive map of DUBs regulating T cell activation and to characterize their point of action. In addition, we will elucidate positive or negative functions of specific candidate DUBs for T cell biology.
DFG-Verfahren
Schwerpunktprogramme
