Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53.
Maehara, Kayoko Yamakoshi, Kimi Ohtani, Naoko Kubo, Yoshiaki Takahashi, Akiko Arase, Seiji Jones, Nic Hara, Eiji
Maehara, Kayoko
Yamakoshi, Kimi
Ohtani, Naoko
Kubo, Yoshiaki
Takahashi, Akiko
Arase, Seiji
Jones, Nic
Hara, Eiji
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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.
Description
Date
2005-02-14
Publisher
Collections
Keywords
Tumour Cells
Tumour Suppressor Protein p53
Tumour Suppressor Protein p53
Type
Article
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.