SPP 1365:  The Regulatory and Functional Network of Ubiquitin Family Proteins

• Subject Area: Biology
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 43455480

Ubiquitin (Ub) has classically been associated with protein degradation via the 26S proteasome.
However, in the past decade various non-proteolytic functions of Ub have been elucidated.
Additionally, the discovery and investigation of Ub family proteins (UbF) such as SUMO, NEDD8, FAT10 or ISG15, the majority of which do not primarily function as signals for proteasomal degradation, have provided important new insights in our understanding of cellular key processes, such as signal transduction, DNA repair, transcriptional regulation or protein trafficking.
The coordinated investigation of the regulatory and functional network of UbF proteins is the major aim of the Priority Programme. The participants will delineate the interplay and interconnection of UbF pathways as a novel regulatory principle for many important biological processes. The ultimate goal is to provide an integrated view of the UbF network, major aims are:
(1) define the regulatory functions of UbF modifications,
(2) identify and characterise novel UbF binding modules,
(3) identify the cellular machineries for UbF conjugation and deconjugation and
(4) elucidate the regulatory network characterised by the interplay and overlap of functions of different UbF members.
To ensure maximal synergy, the Priority Programme aims to focus on regulatory functions of - and crosstalk between - UbF proteins. Therefore, typical studies on polyubiquitin-mediated protein degradation by the 26S proteasome were intentionally excluded. Synergistic effects of the network will be obtained due to the fact:
(1) There is already a strong expertise on important aspects of the biochemistry and cell biology of several UbF proteins, which is represented in the Priority Programme. This expertise is a unique advantage in tackling the challenge of investigating the network functions of the UbF proteins and will be mutually made available to all participants of the Priority Programme.
(2) Several model organisms including fungi, plants and mammalian systems will be employed in order to use the most suitable system for the respective experimental questions regarding specific UbF proteins.
(3) Available genomic information and comparative bioinformatic analyses are an excellent source for predictions of UbF pathway proteins, which now need to be tested in biochemical and biological systems.

• DFG Programme: Priority Programmes
• International Connection: France

Projects

• Analysis of the ISG15 conjugation and deconjugation system in vivo (Applicant Knobeloch, Klaus-Peter )
• Biochemical and functional characterization of ubiquitin-like proteines ISG15 and FAT10 in human dendritic cells. (Applicant Kloetzel, Peter Michael )
• Consequences of ubiquitin E2 enzyme (E2-25K) sumoylation (Applicant Pichler, Ph.D., Andrea )
• Elucidating the function of the deubiquitinating enzyme AMSH3 in cellular trafficking in Arabidopsis thaliana (Applicant Isono, Erika )
• Function of the Ubiquitin-Like Protein Hub1 (Applicant Jentsch, Stefan )
• Function of the UBZ-containing ATPase Wrnip1 in DNA replication and damage response (Applicant Dikic, Ivan )
• Functional characterization of ubiquitin-like modifier ISG15 in murine enterovirus myocarditis (Applicant Beling, Antje )
• Functional consequences of NFATc1 sumoylation on lymphocyte activation, differentiation and tolerance (Applicant Berberich-Siebelt, Friederike )
• Functions of regulatory ubiquitin and ubiquitin-like modifications for NF-kB signalling in T cells (Applicant Krappmann, Ph.D., Daniel )
• Identification and characterization of NEDD8-modified proteins and deneddylases of the filamentous fungs Aspergillus nidulans (Applicant Braus, Gerhard H. )
• Identification and characterization of NEDD8-modified proteins from plants (Applicant Schwechheimer, Claus )
• Koordinationsantrag (Applicant Dubiel, Wolfgang )
• Mechanism and function of protein modifiaction with mixed SUMO1-Ubiquitin chains (Applicant Melchior, Frauke )
• Mechanistic insight into A/B toxin cell entry via ubiquitin-mediated receptor endocytosis (Applicant Schmitt, Manfred Josef )
• Nedd8/COP9 signalosome-dependent control of IkBs and RelA (Applicant Naumann, Michael )
• NEDD8: Mechanisms of conjugation and identification of binding partners (Applicant Scheffner, Martin )
• Proteomic characterization of ubiquitin-dependent processes in the secretory pathway (Applicant Sommer, Thomas )
• Regulation of mitotic spindle positioning trough SUMO and ubiquitin modifications (Applicant Liakopoulos, Ph.D., Dimitris )
• Regulatory functions of the SUMO system in ribosome biogenesis and mitosis (Applicant Müller, Stefan )
• Role of deubiquitinating enzymes (DUBs) in Protein trafficking (Applicant Kölling, Ralf )
• Role of Neddylation in the Adult Central Nervous System: Mechanisms underlying its effects on neurotransmission, synaptic plasticity and behaviours (Applicant Refojo, Damian )
• SUMO-SIM interactions and their role in substrate recognition and autoregulation of SUMO-dependent ubiquitin ligases (Applicant Dohmen, Jürgen )
• The biological function of the COP9 signalosome-mediated deneddylation and deubiquitination (Applicant Dubiel, Wolfgang )
• The functional significance of SUMOylierung in biological timing (Applicant Weber, Frank )
• The role of diSUMO-like DSUL and targets for female gametogenesis and early embryogenesis in maize (Applicant Dresselhaus, Thomas )
• The role of Nedd4 family E3 ubiquitin ligases in the regulation of neuronal cell surface receptors (Applicant Kawabe, Hiroshi )
• The role of the ubiquitin-like protein FAT10 in thymic selection (Applicant Groettrup, Marcus )
• Unconventional ubiquitin chains as regulators of plant development (Applicant Bachmair, Andreas )
• VCP/p97-governed sorting of mono-ubiquitinated proteins in the endocytic pathway (Applicant Meyer, Hemmo )

• Spokesperson: Professor Dr. Wolfgang Dubiel