Objectif Cancer is one of the leading causes of death in Europe and one of the highlighted issues in the 7th Framework Programme. Understanding the molecular mechanisms of cancer is expected to contribute to the development of better therapeutic approaches. In this project, the applicant proposes to examine the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) and its product, fructose-2,6-bisphosphate (F2,6BP), in the regulation of the cell cycle and tumorigenesis. Increased glycolysis is a key metabolic phenotype of cancer. Oncogenic stimuli increase F2,6BP, an activator of the first irreversible step of glycolysis. Previous studies have suggested PFKFB3 to be the dominant source of F2,6BP and the culprit behind the high glycolytic activity in tumors. The applicant has recently demonstrated that PFKFB3 localizes to the nucleus, where PFKFB3-mediated synthesis of F2,6BP stimulates cells to proliferate without a significant effect on glycolysis. He then discovered that F2,6BP in the nucleus activates cyclin-dependent kinases, decreases the expression of the cell cycle suppressor p27, and increases the expression of cyclin D3. These and other previous results obtained by the applicant suggest that tumor cells may need PFKFB3 and F2,6BP in the nucleus in order to couple glucose uptake with cell division activity in the nucleus. The objectives of the project are as follows: 1-To ascertain the role of PFKFB3 in the regulation of the cell cycle and cell cycle proteins; 2-To determine if there is a genetic/functional interaction between PFKFB3 and cyclin D3, and 3-To determine the in vivo interaction of PFKFB3 and p27, and whether PFKFB3 is required for tumor susceptibility induced by p27 deficiency. This project is expected to help the applicant continue his career in his host institution where he can apply the state-of-art techniques he has learned in the USA to contribute to the European Research Area in the field of cancer research. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncology Programme(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) Thème(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Appel à propositions FP7-PEOPLE-2009-RG Voir d’autres projets de cet appel Régime de financement MC-IRG - International Re-integration Grants (IRG) Coordinateur BURSA ULUDAG UNIVERSITESI Contribution de l’UE € 100 000,00 Adresse BURSA ULUDAG UNIVESITESI REKTORLUGU NILUFER 16059 BURSA Turquie Voir sur la carte Région Doğu Marmara Bursa Bursa Type d’activité Higher or Secondary Education Establishments Contact administratif Esvet Acikgoz (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
