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Molecular and Cellular Biology, March 2006, p. 2441-2455, Vol. 26, No. 6
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.6.2441-2455.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The p110 Isoform of the CDP/Cux Transcription Factor Accelerates Entry into S Phase

Laurent Sansregret,1,2 Brigitte Goulet,1,2 Ryoko Harada,1,2 Brian Wilson,1,2 Lam Leduy,1 Jacques Bertoglio,5 and Alain Nepveu1,2,3,4*

Molecular Oncology Group, McGill University Health Center,1 Departments of Biochemistry,2 Oncology,3 Medicine, McGill University, 687 Pine Ave. West, Montreal, Quebec, Canada H3A 1A1,4 INSERM U461, Faculté de Pharmacie, Paris XI, 5 rue Jean Baptiste Clément, 92296 Chatenay-Malabry, France5

Received 26 September 2005/ Returned for modification 31 October 2005/ Accepted 29 December 2005

The CDP/Cux transcription factor was previously found to acquire distinct DNA binding and transcriptional properties following a proteolytic processing event that takes place at the G1/S transition of the cell cycle. In the present study, we have investigated the role of the CDP/Cux processed isoform, p110, in cell cycle progression. Populations of cells stably expressing p110 CDP/Cux displayed a faster division rate and reached higher saturation density than control cells carrying the empty vector. p110 CDP/Cux cells reached the next S phase faster than control cells under various experimental conditions: following cell synchronization in G0 by growth factor deprivation, synchronization in S phase by double thymidine block treatment, or enrichment in G2 by centrifugal elutriation. In each case, duration of the G1 phase was shortened by 2 to 4 h. Gene inactivation confirmed the role of CDP/Cux as an accelerator of cell cycle progression, since mouse embryo fibroblasts obtained from Cutl1z/z mutant mice displayed a longer G1 phase and proliferated more slowly than their wild-type counterparts. The delay to enter S phase persisted following immortalization by the 3T3 protocol and transformation with H-RasV12. Moreover, CDP/Cux inactivation hindered both the formation of foci on a monolayer and tumor growth in mice. At the molecular level, expression of both cyclin E2 and A2 was increased in the presence of p110 CDP/Cux and decreased in its absence. Overall, these results establish that p110 CDP/Cux functions as a cell cycle regulator that accelerates entry into S phase.

* Corresponding author. Mailing address: McGill University Health Center, Molecular Oncology Group, 687 Pine Avenue West, room H5.21, Montreal, Quebec H3A 1A1, Canada. Phone: (514) 934-1934, ext. 35842. Fax: (514) 843-1478. E-mail: alain.nepveu{at}mcgill.ca.

Molecular and Cellular Biology, March 2006, p. 2441-2455, Vol. 26, No. 6
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.6.2441-2455.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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