Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence.
Masashi Narita,Sabrina Nuñez,Sabrina Nuñez,Edith Heard,Masako Narita,Athena W. Lin,Stephen Hearn,David L. Spector,Gregory J. Hannon,Scott W. Lowe +9 more
TLDR
A distinct heterochromatic structure that accumulates in senescent human fibroblasts is described, which is designated senescence-associated heterochROMatic foci (SAHF) and is associated with the stable repression of E2F target genes.About:
This article is published in Cell.The article was published on 2003-06-13 and is currently open access. It has received 2055 citations till now. The article focuses on the topics: Senescence-associated heterochromatin focus & E2F.read more
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Cellular senescence: when bad things happen to good cells
TL;DR: Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.
Journal ArticleDOI
The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression
TL;DR: A senescence-associated secretory phenotype (SASP) is acquired that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression.
Journal ArticleDOI
Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors
Judith Campisi,Judith Campisi +1 more
TL;DR: The senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate.
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BRAFE600-associated senescence-like cell cycle arrest of human naevi
Chrysiis Michaloglou,Liesbeth C.W. Vredeveld,Maria S. Soengas,Christophe Denoyelle,Thomas Kuilman,Chantal M.A.M. van der Horst,Donne Majoor,Jerry W. Shay,Wolter J. Mooi,Daniel S. Peeper +9 more
TL;DR: It is shown that sustained BRAFV600E expression in human melanocytes induces cell cycle arrest, which is accompanied by the induction of both p16INK4a and senescence-associated acidic β-galactosidase (SA-β-Gal) activity, a commonly usedsenescence marker.
Journal ArticleDOI
Aging, Cellular Senescence, and Cancer
TL;DR: The idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence is discussed.
References
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Journal Article
DNA damage is able to induce senescence in tumor cells in vitro and in vivo.
TL;DR: The results suggest that p53 and p21 play a central role in the onset of senescence, whereas p16(INK4a) function may be involved in maintainingSenescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome.
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Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression
TL;DR: This work finds that the pattern of E2F and pRB-related polypeptides recruited to these promoters changes in a strikingly dynamic fashion as cells progress from quiescence into G(1) and S phase, and suggests that repression and activation of E 2F-responsive genes may occur through distinct E2Fs that direct the sequential recruitment of enzymes able to deacetylate and then acetylate core histones.
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Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization
Julien Sage,George J. Mulligan,Laura D. Attardi,Abigail L. Miller,SiQi Chen,Bart O. Williams,Elias Theodorou,Tyler Jacks +7 more
TL;DR: The results confirm the essential role of the Rb family in the control of the G(1)/S transition, place the three R b family members downstream of multiple cell cycle control pathways, and further the link between loss of cell cycle Control and tumorigenesis.
Journal Article
A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents
Bey-Dih Chang,Eugenia V. Broude,Milos Dokmanovic,Hongming Zhu,Adam Ruth,Yongzhi Xuan,Eugene S. Kandel,Ekkehart Lausch,Konstantin Christov,Igor B. Roninson +9 more
TL;DR: SLP induction in breast carcinoma cells treated with retinoids in vitro or in vivo was found to correlate with permanent growth inhibition under the conditions of minimal cytotoxicity, suggesting that this response may be particularly important for the antiproliferative effect of differentiating agents.
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PML is induced by oncogenic ras and promotes premature senescence
Gerardo Ferbeyre,Elisa de Stanchina,Emmanuelle Querido,Nicole Baptiste,Carol Prives,Scott W. Lowe +5 more
TL;DR: It is implied that PML acts with Rb and p53 to promote ras-induced senescence and provide new insights into PML regulation and activity.