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Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2005
- Publisher :
- Rockefeller University Press, 2005.
-
Abstract
- E2F/DP complexes were originally identified as potent transcriptional activators required for cell proliferation. However, recent studies revised this notion by showing that inactivation of total E2F/DP activity by dominant-negative forms of E2F or DP does not prevent cellular proliferation, but rather abolishes tumor suppression pathways, such as cellular senescence. These observations suggest that blockage of total E2F/DP activity may increase the risk of cancer. Here, we provide evidence that depletion of DP by RNA interference, but not overexpression of dominant-negative form of E2F, efficiently reduces endogenous E2F/DP activity in human primary cells. Reduction of total E2F/DP activity results in a dramatic decrease in expression of many E2F target genes and causes a senescence-like cell cycle arrest. Importantly, similar results were observed in human cancer cells lacking functional p53 and pRB family proteins. These findings reveal that E2F/DP activity is indeed essential for cell proliferation and its reduction immediately provokes a senescence-like cell cycle arrest.
- Subjects :
- Chromatin Immunoprecipitation
Cell cycle checkpoint
Cell Cycle Proteins
Electrophoretic Mobility Shift Assay
Retinoblastoma Protein
Report
Tumor Cells, Cultured
Humans
Cell Cycle Protein
E2F
Research Articles
Cellular Senescence
Cell Proliferation
biology
Cell growth
Cell Cycle
Retinoblastoma protein
Cell Biology
Cell cycle
E2F Transcription Factors
Cell biology
DNA-Binding Proteins
stomatognathic diseases
Cancer cell
Cancer research
biology.protein
RNA Interference
Tumor Suppressor Protein p53
biological phenomena, cell phenomena, and immunity
Transcription Factor DP1
Cell aging
HeLa Cells
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 15408140 and 00219525
- Volume :
- 168
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....a8237ed3403fbb8fbb8a59d8671edc82
- Full Text :
- https://doi.org/10.1083/jcb.200411093