Detailseite
Projekt
Nedd8/COP9 signalosome-dependent control of IkBs and RelA
Antragsteller
Professor Dr. Michael Naumann
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2008 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 72025323
Activation and control of the ubiquitous transcription factor nuclear factor kappa B (NF-κB) involves complex signal transduction processes. Our recent results have shown that the multiprotein complex COP9 signalosome (CSN) exerts certain functions in the control of the NF-κB activity in tumour necrosis factor receptor (TNFR) and T-cell receptor (TCR)-stimulated cells. The CSN possesses an intrinsic metalloprotease activity, which allows the removal of the Ubiquitin-like (Ubl) protein NEDD8 (deneddylation) from Cullin-RING ubiquitin-ligases (CRLs). Further, the CSN associates with deubiquitinylases (DUBs), which regulate the activity of CRLs and there substrate molecules. To date, the CSN-dependent processes, which control the NF-κB transcription factor RelA, and the Ubl- as well as DUB-dependent mechanisms in the control of the NF-κB system are incompletely understood. In the research proposal we plan to address the following topics in TNFR-induced cells i) analysis of the impact of the CSN, Ubiquitin and Ubls on RelA regulation, ii) identification of regulatory NF-κB factors, which are targeted by Ubls and iii) characterisation of the regulatory functions of DUBs in the NF-κB system and performance of a DUB-specific siRNA screen comprising all known human DUBs. Taken together, the proposed project could reveal novel insights into CSN-, Ubiquitin-, Ubl- and DUB-dependent regulatory functions in the NF-κB system.
DFG-Verfahren
Schwerpunktprogramme
