Koordinationsantrag

在过去的3年中，DFG的资助使得德国在泛素家族（UbF）蛋白（如Ub本身和Ub样（Ubl）蛋白Nedd 8、SUMO、FAT 10、ISG 15等）的翻译后修饰方面的研究工作得到了实质性的加强。特别是，在该项目过去的资助期间，对构成所谓UbF网络的不同UbF蛋白之间相互作用的研究受到了越来越多的关注。很明显，例如Ub，Nedd 8和SUMO途径不是分开的，并且给定蛋白质上的这些翻译后修饰不是相互排斥的。相反，在从细胞周期控制、DNA修复、发育到信号转导的基本细胞过程中存在许多串扰的例子（最近的综述见[1-9]）。项目成员的成就（见附录：由个人参与者或项目参与者之间合作产生的选定出版物）对该领域的发展做出了重大贡献。Groettrup实验室[10]对泛素和FAT 10的双特异性缀合酶的鉴定或Dohmen/Praefcke实验室[11]对SUMO依赖性泛素化的研究很好地证实了UbF修饰系统的相互作用。自噬途径与泛素系统的相互连接，作为UbF网络中的新调控层出现，也被项目成员的出版物所涵盖[12，13]。Marcus Groettrup编辑的一本书的出版强调了项目成员的共同活动，也可能有助于提高该计划的国际知名度[7]。这本书，题为“共轭和解共轭的泛素家族修饰剂”，突出了最近的发展，在UbF领域和包含的贡献，由成员的项目：伊万Dikic，沃尔夫冈Dubiel，丹尼尔Krappmann，马丁Scheffner，斯特凡Jentsch，斯特凡穆勒，Gerrit Praefcke，Jürgen Dohmen，克劳斯-彼得Knobeloch和马库斯Groettrup。 未来申请期的主要目标仍然是协调研究UbF蛋白的调控和功能网络，如SUMO，Nedd 8，FAT 10和ISG 15。该项目的主要重点将是阐明UbF途径之间的相互作用和相互联系。该项目的最终目标是提供UbF网络的综合视图。为此，UbF网络优先计划旨在： (1)鉴定新UbF修饰蛋白， (2)定义这些修饰的调节功能， (3)鉴定和表征新UbF结合模块， (4)鉴定用于UbF缀合和解缀合的细胞机制，以及 (5)阐明调控网络的特点是不同的UbF成员的功能的相互作用和重叠。 根据第一个申请期的协同效应，项目成员之间开展了新的合作，将通过项目提供资金予以支持。

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.