The functional interplay between the COP9 signalosome-mediated deneddylation and the cullin-RING ubiquitination

Posttranslational modification of target proteins by members of the ubiquitin (Ub) protein family (UbF) such as Nedd8, SUMO, Ub etc. is a common regulatory principle in eukaryotic cells. A major aim of the DFG priority program SPP1365 on the UbF network is to delineate the interconnection of different UbF pathways and to elucidate the role of the regulatory network comprised of several UbF modifications in essential cellular functions. In the current project we will investigate the interplay between cullin modification by Nedd8 and ubiquitination of proteins. In particular, we will characterize the role of the COP9 signalosome (CSN) as a major deconjugating enzyme complex in eukaryotic cells removing Nedd8 from cullins. We will study the impact of phorphorylation and of protein interactions on the CSN-mediated deneddylation in vitro and in mammalian cells. Using the Crystallography module of the SPP1365 we will analyze CSN sub-complex structures to understand the mechanism of the CSN deneddylating activity. By using the Mouse genetics module of the SPP1365 we will establish a transgenic mouse model defective in CSN-mediated deneddylation to study its impact on mouse development and organ functions.
Head of Project:

Univ. Prof. Dr. Wolfgang Dubiel
Charité - Universitätsmedizin Berlin
Department of General, Visceral, Vascular and Thoracic Surgery CCM
Tel. 450-522305
Fax 450-522928
Additional Head of Project:

Additional Member of Project:

Tilo Schmaler, Ronny Hannss
Begin/End of Project:

06/2008 - 12/2010
Funded by:

Deutsche Forschungsgemeinschaft e.V.