Objective Ubiquitin (Ub) is a small modifier that labels proteins in a highly specific manner. Like phosphorylation, modification of proteins by Ub is prevalent in the majority of cellular processes. An increasing number of distinct functions have been assigned to different types of ubiquitin modifications (monoUb and different Lys-linked chains). Moreover, aberrations in the ubiquitin system underlie many disease states, including cancer, inflammatory, immune and metabolic disorders as well as neurodegeneration. The most recently described physiological ubiquitin modification is the linear ubiquitin chain, in which ubiquitin monomers are conjugated via Met-Gly linkages. We have found that linear ubiquitin chains bind specifically to the NEMO adaptor molecule, an event critical for the proper regulation of NF-ºB signaling (Rahighi, 2009). Here we propose to use a multidisciplinary strategy to study the role of linear ubiquitination in the NF-ºB pathway, autophagy, apoptosis and DNA repair and how these changes can impact on disease states such as inflammation and cancer development. Scientific objectives are: " Characterize the components of linear ubiquitination: E3 ligases, specific substrates and domains recognizing linear ubiquitin chains " Elucidate the in vivo role of linear ubiquitination in the regulation of the NF-ºB pathway, apoptosis and DNA repair. " Reveal the molecular basis for the connections between linear ubiquitination and selective autophagy " Identify elements in the linear ubiquitin network as potential drug targets " Generate transgenic mouse models of inflammatory diseases and cancer " Develop system and computational biology approaches to assess the global role of linear ubiquitination in cellular proteome Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-ID1 - ERC Advanced Grant Interdisciplinary Panel Call for proposal ERC-2009-AdG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN EU contribution € 2 440 560,00 Address THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main Germany See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Ivan Dikic (Prof.) Administrative Contact Kristina Wege (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Germany EU contribution € 2 440 560,00 Address THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Ivan Dikic (Prof.) Administrative Contact Kristina Wege (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
