2005年2月
Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
JOURNAL OF CELL BIOLOGY
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- 巻
- 168
- 号
- 4
- 開始ページ
- 553
- 終了ページ
- 560
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1083/jcb.200411093
- 出版者・発行元
- ROCKEFELLER UNIV PRESS
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.
- リンク情報
- ID情報
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- DOI : 10.1083/jcb.200411093
- ISSN : 0021-9525
- Web of Science ID : WOS:000227101100021