Objective Cyclins play role in the cell division machinery and dictate the proceeding of cell cycle phases. D-type cyclins activity is required for progression through G1 phase, the critical step when cells steer the wheel to enter a new cycle of proliferation, to exit cell cycle and become quiescent or ultimately to differentiate. Generation of mice nullizygous for each of the three D-cyclin genes revealed their physiological impact as well as protective effect against cancer. Cyclin D1 is important during nervous system development, in particular for the retina and the cerebellum. However, cyclin D1 is also directly involved in the proliferative response of estrogen receptor alpha positive breast cancers and over-expressed in HER2 (ERBB2) dependent breast cancers. Recently, we reported a genome-wide function for cyclin D1 in transcriptional regulation, acting physiologically during retinal development. To affect protein production, it has been reported that transcriptional regulatory events need to be coupled with the nuclear export machinery, optimizing transfer of neo-synthesized RNAs to the cytoplasm. This suggests transcription and RNA export are spatially and temporally interconnected rather than stochastic separated phenomena. Hence, we intend to define how cyclin D1 activity governs interactions between the nuclear export and transcriptional machinery during nervous development in comparison to cancer situation. This research project relies on innovative genetics thanks to tandem tagged (Flag-HA) cyclin D1 mice model, together with modern proteomics and genomics approaches. We explore the transcriptional loop operating during cerebellum development in comparison to medulloblastoma genesis, and we extend our study to ERBB2 and ER-dependant breast cancer on the other hand. Demonstrating the mechanism of action between D-cyclins, nuclear pore complexes and transcription factors in this context, will highlight new oncogenic cell cycle components of theranostic potential. Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineophthalmologymedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesgeneticsRNA 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) Topic(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Call for proposal FP7-PEOPLE-2010-RG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS EU contribution € 100 000,00 Address RUE MICHEL ANGE 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Jocelyn Mere (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
