Objetivo The concept of the proteostasis network (PN) represent a systems biology approach to protein deposition diseases (e.g. neurodegenerative diseases, amyloidoses, type II diabetes). The PN includes all the cellular components involved in the synthesis, folding, and degradation of proteins, as well as the regulatory mechanisms required for maintaining a functioning proteome despite cellular stress, mutations, or protein misfolding.When the misfolded protein load exceeds the capacity of the PN to maintain, protein aggregation can occur. Protein misfolding and subsequent aggregation is already thought to be the main cause of neuronal death in neurodegenerative diseases. Our study on the aggregation of p53, however, is the first report of protein aggregation leading directly to increased cell proliferation of the same cell in which the aggregation occurs by a gain of function mechanism.p53 is a potent tumor suppressor, and it is the most frequently mutated gene in human cancer (approximately half of the cases). We observed that mutant p53 not only strongly aggregated in tumor cells, - thereby already eliminating one copy of p53 – but that it also co-aggregated in a dominant negative way with wild type p53 and its paralogs, p63 and p73, sequestering these tumor suppressors that are pivotal to prevent tumorigenesis.The ability of the PN to cope with mutant or damaged biological material varies with the differentiation stage of cells, as well as deteriorates with cellular senescence. According to our hypothesis, the decline of the PN, particularly its decreasing ability to control aggregation-prone mutant p53 proteins, is one of the contributing factors to the steadily increasing incidence of cancer with age.We are proposing to study the aggregation of mutant p53 proteins in undifferentiated, differentiated, and senescent cells to test our hypothesis and gain information on the key factors keeping p53 aggregation, and tumorigenesis, at bay. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesmolecular biologystructural biology Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) FP7-PEOPLE-2011-IIF - Marie Curie Action: "International Incoming Fellowships" Convocatoria de propuestas FP7-PEOPLE-2011-IIF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IIF - International Incoming Fellowships (IIF) Coordinador VIB VZW Aportación de la UE € 235 000,00 Dirección SUZANNE TASSIERSTRAAT 1 9052 ZWIJNAARDE - GENT Bélgica Ver en el mapa Región Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Tipo de actividad Research Organisations Contacto administrativo Rik Audenaert (Mr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos