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.
Journal ArticleDOI
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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Reversal of Senescence in Mouse Fibroblasts through Lentiviral Suppression of p53
Annette M.G. Dirac,René Bernards +1 more
TL;DR: It is shown that suppression of p53 expression in senescent MEFs leads to rapid cell cycle re-entry, is associated with loss of expression of senescence-associated genes, and leads to immortalization.
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INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence.
Sharon Brookes,Janice Rowe,Margarida Ruas,Susana Llanos,Paula A. Clark,Martine Lomax,Marion C. James,Radost Vatcheva,Stewart Bates,Karen H. Vousden,David A.D. Parry,Nelleke A. Gruis,Nico P.M. Smit,Wilma Bergman,Gordon Peters +14 more
TL;DR: It is found that in human fibroblasts, ARF is not induced demonstrably by RAS, pointing to significant differences between the proliferative barriers implemented by the CDKN2A locus in different cell types or species.
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Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein–methyltransferase superfamily
George Steele-Perkins,George Steele-Perkins,Wei Fang,Xiao-Hong Yang,Mireille Van Gele,Tobias Carling,Jian Gu,Inge M. Buyse,Inge M. Buyse,Jonathon A. Fletcher,Jinsong Liu,Roderick T. Bronson,Robert B. Chadwick,Albert de la Chapelle,Xiao-kun Zhang,Frank Speleman,Shi Huang +16 more
TL;DR: A direct link between tumor formation and the MTase domain of RIZ1 is suggested and for the first time a tumor susceptibility gene among methyltransferases is described, involved in chromatin-mediated gene expression.
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p16 INK4a can initiate an autonomous senescence program.
Charlotte Y. Dai,Greg H. Enders +1 more
TL;DR: It is demonstrated that a sustained period of p16INK4a expression is sufficient in this setting to impose a durable block to cell proliferation and that this state becomes independent of p 16INK 4a expression, hypophosphorylation of pRB, or a strict G1 arrest.