Objectif Protein serine/threonine phosphatases (PSTPs) are considered undruggable although they are involved in the most prominent post-translational modifications. This is mainly due to an apparent lack of substrate specificity. One important PSTP is protein phosphatase-1 (PP1), a ubiquitous PSTP that is predicted to catalyze about 1/3rd of Ser and Thr dephosphorylations in eukaryotic cells, counteracting hundreds of kinases. PP1 has broad substrate specificity but is restrained in vivo by numerous PP1-interacting proteins functioning for example as substrate-targeting proteins and forming specific holoenzymes with PP1. PP1 holoenzymes play a role in many different diseases such as cancer (counteracting oncogenic kinases), diabetes (insulin release), Alzheimer’s (dephosphorylation of Tau protein) and HIV (viral translation). Currently, there are no chemical modulators available that target PP1 selectively, except that we recently developed the first compound that selectively activates PP1 in intact cells, leading to rapid dephosphorylation of PP1 substrates. The activator does not act on the most closely related protein phosphatase-2A. This proposal aims to generate and apply tools for the investigation of PP1, in part based on our previously developed activator. The tools include selective, photo- and enzymatically releasable chemical inhibitors and activators and semisynthetic proteins, and they will be applied to study PP1–substrate interactions and help identify the correlating interacting proteins. The proposed research will provide long-sought selective chemical tools to study PP1 by applying new concepts of activator and inhibitor design using peptide and small molecule chemistry to an enzyme class that is difficult to be targeted chemically. This research program will contribute to a much more detailed understanding of PP1 biology, and will open doors to investigate PP1 and its holoenzymes as drug targets. Champ scientifique medical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesclinical medicineendocrinologydiabetesmedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes 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) Thème(s) ERC-SG-PE5 - ERC Starting Grant - Materials and Synthesis Appel à propositions ERC-2013-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil ALBERT-LUDWIGS-UNIVERSITAET FREIBURG Contribution de l’UE € 488 332,76 Adresse FAHNENBERGPLATZ 79098 Freiburg Allemagne Voir sur la carte Région Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Type d’activité Higher or Secondary Education Establishments Chercheur principal Maja Banks-Köhn (Prof.) Contact administratif Christian Jäger (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire ALBERT-LUDWIGS-UNIVERSITAET FREIBURG Allemagne Contribution de l’UE € 488 332,76 Adresse FAHNENBERGPLATZ 79098 Freiburg Voir sur la carte Région Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Type d’activité Higher or Secondary Education Establishments Chercheur principal Maja Banks-Köhn (Prof.) Contact administratif Christian Jäger (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée EUROPEAN MOLECULAR BIOLOGY LABORATORY Allemagne Contribution de l’UE € 676 183,24 Adresse Meyerhofstrasse 1 69117 Heidelberg Voir sur la carte Région Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Type d’activité Research Organisations Contact administratif Virginia Otón García (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée