This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sansregret, L. Articles by Nepveu, A. Search for Related Content PubMed PubMed Citation Articles by Sansregret, L. Articles by Nepveu, A.

 Previous Article  |  Next Article 

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

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 Cutl1^z/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-Ras^V12. 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.

This article has been cited by other articles:

• Cadieux, C., Harada, R., Paquet, M., Cote, O., Trudel, M., Nepveu, A., Bouchard, M. (2008). Polycystic Kidneys Caused by Sustained Expression of Cux1 Isoform p75. J. Biol. Chem. 283: 13817-13824 [Abstract] [Full Text]  
• Truscott, M., Harada, R., Vadnais, C., Robert, F., Nepveu, A. (2008). p110 CUX1 Cooperates with E2F Transcription Factors in the Transcriptional Activation of Cell Cycle-Regulated Genes. Mol. Cell. Biol. 28: 3127-3138 [Abstract] [Full Text]  
• Goulet, B., Markovic, Y., Leduy, L., Nepveu, A. (2008). Proteolytic Processing of Cut Homeobox 1 by Neutrophil Elastase in the MV4;11 Myeloid Leukemia Cell Line. Mol Cancer Res 6: 644-653 [Abstract] [Full Text]  
• Stratigopoulos, G., Padilla, S. L., LeDuc, C. A., Watson, E., Hattersley, A. T., McCarthy, M. I., Zeltser, L. M., Chung, W. K., Leibel, R. L. (2008). Regulation of Fto/Ftm gene expression in mice and humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294: R1185-R1196 [Abstract] [Full Text]  
• Harada, R., Vadnais, C., Sansregret, L., Leduy, L., Berube, G., Robert, F., Nepveu, A. (2008). Genome-wide location analysis and expression studies reveal a role for p110 CUX1 in the activation of DNA replication genes. Nucleic Acids Res 36: 189-202 [Abstract] [Full Text]  
• Truscott, M., Denault, J.-B., Goulet, B., Leduy, L., Salvesen, G. S., Nepveu, A. (2007). Carboxyl-terminal Proteolytic Processing of CUX1 by a Caspase Enables Transcriptional Activation in Proliferating Cells. J. Biol. Chem. 282: 30216-30226 [Abstract] [Full Text]  
• Goulet, B., Sansregret, L., Leduy, L., Bogyo, M., Weber, E., Chauhan, S. S., Nepveu, A. (2007). Increased Expression and Activity of Nuclear Cathepsin L in Cancer Cells Suggests a Novel Mechanism of Cell Transformation. Mol Cancer Res 5: 899-907 [Abstract] [Full Text]  
• Ripka, S, Konig, A, Buchholz, M, Wagner, M, Sipos, B, Kloppel, G, Downward, J, Gress, T., Michl, P (2007). WNT5A--target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer. Carcinogenesis 28: 1178-1187 [Abstract] [Full Text]  
• Cadieux, C., Fournier, S., Peterson, A. C., Bedard, C., Bedell, B. J., Nepveu, A. (2006). Transgenic Mice Expressing the p75 CCAAT-Displacement Protein/Cut Homeobox Isoform Develop a Myeloproliferative Disease-Like Myeloid Leukemia. Cancer Res. 66: 9492-9501 [Abstract] [Full Text]