Obiettivo The ubiquitin editing protein A20, a novel 90kDa zinc-finger protein has an universal anti-inflammatory activity by inhibiting NF-kappaB activation. In endothelial cells, the induction of A20 by inflammatory stimuli renders cells resistant to apoptosis. However, A20 can have pro-apoptotic activities in other cell types. We will focus on the respective role of A20 in both endothelial cells and neutrophils, two cardinal cell players in inflammation associated with autoimmune vasculitis in which A20 could be a suitable therapeutic target and has never been investigated. We hypothesized that this differential effect of A20 in modulating apoptosis and inflammation is dependent on different molecular partner A20. Hence, we proposeto i) identify the A20 interactome by proteomic and modelisation approaches in both endothelial cells and neutrophils, ii) investigate the function of A20 in neutrophils, iii) study A20 modulation of neutrophil-mediated endothelial cell toxicity, iii) investigate A20 expression in patients with vasculitis. Through its interdisciplinary and integrative approaches combining molecular biology, cell biology, functional biology, molecular modeling and clinical investigations, this project directed by Dr Daniel, an expert of A20, constitutes a timely and novative approach to unravel the role of A20 and A20-binding proteins in modulating apoptosis and inflammation and identify novel therapeutic tools. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesmolecular biology Parole chiave A20 protein NF-kappa B Wegener granulomatosis adenovirus apoptosis endothelial cell inflammation interactome neutrophil proteinase 3 proteomic ubiquitin vasculitis Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) PEOPLE-2007-4-3.IRG - Marie Curie Action: "International Reintegration Grants" Invito a presentare proposte FP7-PEOPLE-2007-4-3-IRG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IRG - International Re-integration Grants (IRG) Coordinatore INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contributo UE € 100 000,00 Indirizzo RUE DE TOLBIAC 101 75654 Paris Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Annick Bertault (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato