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

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 rat...

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Main Authors:	Maehara, Kayoko, Yamakoshi, Kimi, Ohtani, Naoko, Kubo, Yoshiaki, Takahashi, Akiko, Arase, Seiji, Jones, Nic, Hara, Eiji
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2005
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171766/

id	pubmed-2171766
recordtype	oai_dc
spelling	pubmed-21717662008-03-05 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 Research Articles 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. The Rockefeller University Press 2005-02-14 /pmc/articles/PMC2171766/ /pubmed/15716376 http://dx.doi.org/10.1083/jcb.200411093 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Maehara, Kayoko Yamakoshi, Kimi Ohtani, Naoko Kubo, Yoshiaki Takahashi, Akiko Arase, Seiji Jones, Nic Hara, Eiji
spellingShingle	Maehara, Kayoko Yamakoshi, Kimi Ohtani, Naoko Kubo, Yoshiaki Takahashi, Akiko Arase, Seiji Jones, Nic Hara, Eiji Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
author_facet	Maehara, Kayoko Yamakoshi, Kimi Ohtani, Naoko Kubo, Yoshiaki Takahashi, Akiko Arase, Seiji Jones, Nic Hara, Eiji
author_sort	Maehara, Kayoko
title	Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
title_short	Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
title_full	Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
title_fullStr	Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
title_full_unstemmed	Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53
title_sort	reduction of total e2f/dp activity induces senescence-like cell cycle arrest in cancer cells lacking functional prb and p53
description	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.
publisher	The Rockefeller University Press
publishDate	2005
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171766/
_version_	1611424708526342144

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

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