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
Citations
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Feedback between p21 and reactive oxygen production is necessary for cell senescence
João F. Passos,Glyn Nelson,Chunfang Wang,Torsten Richter,Cedric Simillion,Carole J. Proctor,Satomi Miwa,Sharon Olijslagers,Jennifer Hallinan,Anil Wipat,Gabriele Saretzki,Karl Lenhard Rudolph,Thomas B. L. Kirkwood,Thomas von Zglinicki +13 more
TL;DR: There exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of ‘deep’ cellular senescence, and is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype.
Journal ArticleDOI
Senescence-messaging secretome: SMS-ing cellular stress
Thomas Kuilman,Daniel S. Peeper +1 more
TL;DR: Recently emerging evidence points to a crucial role in oncogene-induced cellular senescence for the 'senescence-messaging secretome' or SMS, setting the stage for cross-talk between senescent cells and their environment.
Journal ArticleDOI
The E2F transcriptional network: old acquaintances with new faces.
TL;DR: How the discovery of new family members with unusual properties, the unexpected phenotypes of mutant animals, a diverse collection of biological activities, a large number of new putative target genes and the new modes of transcriptional regulation are described will shape a new and revised picture of the E2F transcriptional program.
Journal ArticleDOI
Forging a signature of in vivo senescence
TL;DR: It is advocated that more-specific descriptors be substituted for the now broadly applied umbrella term 'senescence' in defining the suite of diverse physiological responses to cellular stress.
Journal ArticleDOI
Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity
Yuchen Chien,Claudio Scuoppo,Xiaowo Wang,Xueping Fang,Brian M. Balgley,Jessica E. Bolden,Prem K. Premsrirut,Weijun Luo,Agustin Chicas,Cheng S. Lee,Scott C. Kogan,Scott W. Lowe +11 more
TL;DR: It is found that NF-κB acts as a master regulator of the SASP, influencing the expression of more genes than RB and p53 combined, and a tumor-suppressive function of NF-σB that contributes to the outcome of cancer therapy is identified.
References
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A biomarker that identifies senescent human cells in culture and in aging skin in vivo
Goberdhan P. Dimri,X Lee,G Basile,Meileen Acosta,G Scott,C Roskelley,E E Medrano,Maarten H.K. Linskens,Ivica Rubelj,Olivia M. Pereira-Smith +9 more
TL;DR: It is shown that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture, which provides in situ evidence that senescent cells may exist and accumulate with age in vivo.
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The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
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Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
TL;DR: It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
Andrew J. Bannister,Philip Zegerman,Janet F. Partridge,Eric A. Miska,Jean O. Thomas,Robin C. Allshire,Tony Kouzarides +6 more
TL;DR: A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.