Document Detail

The p110 isoform of the CDP/Cux transcription factor accelerates entry into S phase.
MedLine Citation:
PMID:  16508018     Owner:  NLM     Status:  MEDLINE    
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.
Laurent Sansregret; Brigitte Goulet; Ryoko Harada; Brian Wilson; Lam Leduy; Jacques Bertoglio; Alain Nepveu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  26     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-01     Completed Date:  2006-06-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2441-55     Citation Subset:  IM    
McGill University Health Center, Molecular Oncology Group, 687 Pine Avenue West, room H5.21, Montreal, Quebec H3A 1A1, Canada.
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MeSH Terms
3T3 Cells
Carcinogenicity Tests
Cell Proliferation
Cell Transformation, Neoplastic
Cells, Cultured
Cyclin A / genetics,  metabolism
Cyclin A2
Cyclins / genetics,  metabolism
Fibroblasts / cytology
Genes, ras
Homeodomain Proteins / genetics,  metabolism*
Mice, Mutant Strains
Mice, Nude
Nuclear Proteins / genetics,  metabolism*
Protein Isoforms
Repressor Proteins / genetics,  metabolism*
S Phase / physiology*
Thymidine / metabolism
Transcription Factors / genetics,  metabolism*
Reg. No./Substance:
0/CCNA2 protein, mouse; 0/Ccne2 protein, mouse; 0/Cutl1 protein, mouse; 0/Cyclin A; 0/Cyclin A2; 0/Cyclins; 0/Homeodomain Proteins; 0/Nuclear Proteins; 0/Protein Isoforms; 0/Repressor Proteins; 0/Transcription Factors; 50-89-5/Thymidine

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