CYCLOCK

Cell cycle clock in nervous system and cancer

Coordinatore	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE    more  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Mr. Nome: Jocelyn Cognome: Mere Email: send email Telefono: +33 4 67613535 Fax: +33 4 67043236
Nazionalità Coordinatore	France [FR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-RG
Funding Scheme	MC-IRG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-03-01   -   2015-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Mr. Nome: Jocelyn Cognome: Mere Email: send email Telefono: +33 4 67613535 Fax: +33 4 67043236	FR (PARIS)	coordinator	100˙000.00

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 Obiettivo del progetto (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.'