Cyclin E restores p53 activity in contact-inhibited cells.
The wild-type p53 protein is a potent growth suppressor when overexpressed in vitro. It functions as a transcriptional activator and causes growth arrest at the G1/S stage of the cell cycle. We monitored p53 transactivation as an indicator of p53 function throughout the cell cycle. We first demonstrate that cells which exhibited contact inhibition of growth lacked p53 transactivation function at high cell density. Since these cells were noncycling, we examined whether the ectopic expression of any cyclin could override contact inhibition of growth and restore p53 transactivation function. The transfection of cyclin E at high cell density stimulated the progression of cells through the cell cycle and restored p53 transactivation function. The transcriptional activity of p53 induced by cyclin E was regulated at the level of DNA binding. Cells that did not show contact inhibition of growth had a functional p53 regardless of cell density. Thus, contact inhibition of cell growth corresponded to a lack of p53 transactivation function and the overexpression of cyclin E in these contact-inhibited cells stimulated cell cycle progression and resulted in p53 transcriptional activity.
Deffie
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Department of Molecular Genetics, M. D. Anderson Cancer Center, University of Texas, Houston 77030, USA.
Hao
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M
Montes de Oca Luna
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R
Hulboy
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Lozano
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G
D016475:3T3 Cells; D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002452:Cell Count; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D003260:Contact Inhibition / Q000235:genetics / Q000502:physiology*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000235:genetics; D011994:Recombinant Proteins; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016213:Cyclins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53