Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53.

2.50
Hdl Handle:
http://hdl.handle.net/10541/75660
Title:
Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53.
Authors:
Maehara, Kayoko; Yamakoshi, Kimi; Ohtani, Naoko; Kubo, Yoshiaki; Takahashi, Akiko; Arase, Seiji; Jones, Nic; Hara, Eiji
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.
Affiliation:
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, England, UK.
Citation:
Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53. 2005, 168 (4):553-60 J. Cell Biol.
Journal:
The Journal of Cell Biology
Issue Date:
14-Feb-2005
URI:
http://hdl.handle.net/10541/75660
DOI:
10.1083/jcb.200411093
PubMed ID:
15716376
Type:
Article
Language:
en
ISSN:
0021-9525
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMaehara, Kayoko-
dc.contributor.authorYamakoshi, Kimi-
dc.contributor.authorOhtani, Naoko-
dc.contributor.authorKubo, Yoshiaki-
dc.contributor.authorTakahashi, Akiko-
dc.contributor.authorArase, Seiji-
dc.contributor.authorJones, Nic-
dc.contributor.authorHara, Eiji-
dc.date.accessioned2009-07-24T15:35:19Z-
dc.date.available2009-07-24T15:35:19Z-
dc.date.issued2005-02-14-
dc.identifier.citationReduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53. 2005, 168 (4):553-60 J. Cell Biol.en
dc.identifier.issn0021-9525-
dc.identifier.pmid15716376-
dc.identifier.doi10.1083/jcb.200411093-
dc.identifier.urihttp://hdl.handle.net/10541/75660-
dc.description.abstractE2F/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.en
dc.language.isoenen
dc.subjectTumour Cellsen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshCell Aging-
dc.subject.meshCell Cycle-
dc.subject.meshCell Cycle Proteins-
dc.subject.meshCell Proliferation-
dc.subject.meshChromatin Immunoprecipitation-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshE2F Transcription Factors-
dc.subject.meshElectrophoretic Mobility Shift Assay-
dc.subject.meshHela Cells-
dc.subject.meshHumans-
dc.subject.meshRNA Interference-
dc.subject.meshRetinoblastoma Protein-
dc.subject.meshSignal Transduction-
dc.subject.meshTranscription Factor DP1-
dc.subject.meshTranscription Factors-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshTumor Suppressor Protein p53-
dc.titleReduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, England, UK.en
dc.identifier.journalThe Journal of Cell Biologyen

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