Koordinationsantrag

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In the past 3 years, funding by the DFG has allowed to substantially strengthen research efforts in Germany with regard to posttranslational modifications by ubiquitin family (UbF) proteins such as Ub itself and the Ub-like (Ubl) proteins Nedd8, SUMO, FAT10, ISG15, etc.. In particular, investigations on the interplay between different UbF proteins constituting the so-called UbF network have gained increasing attention during the past funding period of the project. It became clear that for example Ub, Nedd8 and SUMO pathways are not separated and that these posttranslational modifications on a given protein are not mutually exclusive. On the contrary, many examples exist for their cross-talk in essential cellular processes ranging from cell cycle control, DNA repair, development to signal transduction (for recent reviews see [1-9]). Accomplishments by members of the project (see Appendix: Selected publications generated by individual participants or in collaboration between participants of the project) significantly contributed to the development of the field. The identification of a bispecific conjugating enzyme for ubiquitin and FAT10 by the Groettrup laboratory [10] or work on SUMO-dependent ubiquitination by the Dohmen/Praefcke laboratories [11] nicely exemplifies the interplay of UbF modification systems. The interconnection of the autophagy pathway with the ubiquitin system, which emerged as a new regulatory layer in the UbF network, was also covered by publications from the project members [12, 13]. Publication of a book edited by Marcus Groettrup underlines the common activities of the project members and may also help to increase the international visibility of this program [7]. This book, entitled “Conjugation and Deconjugation of Ubiquitin Family Modifiers”, highlights recent developments in the UbF field and contained contributions by members of the project: Ivan Dikic, Wolfgang Dubiel, Daniel Krappmann, Martin Scheffner, Stefan Jentsch, Stefan Müller, Gerrit Praefcke, Jürgen Dohmen, Klaus-Peter Knobeloch und Marcus Groettrup. The major aim of the coming application period continues to be the coordinated investigation of the regulatory and functional network of UbF proteins such as SUMO, Nedd8, FAT10 and ISG15. The main focus of the project will be on the elucidation of the interplay and interconnection between UbF pathways. The ultimate goal of the project is to provide an integrated view of the UbF network. To this end, the UbF network priority program aims to: (1) identify novel UbF-modified proteins, (2) define the regulatory functions of these modifications, (3) identify and characterize novel UbF binding modules, (4) identify the cellular machineries for UbF conjugation and deconjugation, and (5) elucidate the regulatory network characterized by the interplay and overlap of functions of different UbF members. Based on synergic effects in the first application period new collaborations between members of the project have been developed that shall be supported by funding through the project.