Koordinationsantrag

在过去的3年里，在DFG的资助下，德国大大加强了对泛素家族（UbF）蛋白（如Ub本身和Ub样（Ubl）蛋白Nedd8、SUMO、FAT10、ISG15等）翻译后修饰的研究。特别是对构成所谓UbF网络的不同UbF蛋白之间相互作用的研究，在项目过去的资助期间得到了越来越多的关注。很明显，例如Ub， Nedd8和SUMO途径并不是分开的，并且给定蛋白质上的这些翻译后修饰并不是相互排斥的。相反，在细胞周期控制、DNA修复、发育和信号转导等基本细胞过程中，它们的串音存在许多例子（最近的综述见[1-9]）。项目成员的成就（见附录：项目参与者个人或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FAT10双特异性偶联酶的鉴定或Dohmen/Praefcke实验室[11]对sumo依赖性泛素化的研究很好地说明了UbF修饰系统的相互作用。自噬通路与泛素系统的相互连接，作为UbF网络中一个新的调控层，也被项目成员的出版物所覆盖[12,13]。由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b[7]的国际知名度。这本名为“泛素家族修饰词的共轭和解共轭”的书，突出了泛素领域的最新发展，并包含了该项目成员的贡献：Ivan Dikic， Wolfgang Dubiel, Daniel krapmann, Martin Scheffner, Stefan Jentsch, Stefan m<e:1> ller, Gerrit Praefcke, j<s:1> rgen Dohmen， Klaus-Peter Knobeloch和Marcus Groettrup。即将到来的申请期的主要目的仍然是协调研究UbF蛋白如SUMO、Nedd8、FAT10和ISG15的调控和功能网络。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网络的集成视图。为此，UbF网络优先项目旨在：(1)鉴定新的UbF修饰蛋白，(2)定义这些修饰的调控功能，(3)鉴定和表征新的UbF结合模块，(4)鉴定UbF偶联和解偶联的细胞机制，(5)阐明以不同UbF成员功能相互作用和重叠为特征的调控网络。基于首个申请期的协同效应，项目成员之间将发展新的合作关系，并由项目资助。

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.