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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Cancer: crime and punishment.
TL;DR: This work shows that cellular senescence is a defining feature of Ras-initiated premalignant tumours; this could prove valuable in the diagnosis and prognosis of cancer.
Journal ArticleDOI
Induction of p53-Dependent Senescence by the MDM2 Antagonist Nutlin-3a in Mouse Cells of Fibroblast Origin
Alejo Efeyan,Ana Ortega-Molina,Susana Velasco-Miguel,Daniel Herranz,Lyubomir T. Vassilev,Manuel Serrano +5 more
TL;DR: It is reported that nutlin-3a induces cellular senescence in murine primary fibroblasts, oncogenically transformed fibro Blasts, and fibrosarcoma cell lines, and no evidence of drug-induced apoptosis was observed.
Journal ArticleDOI
Assessing Cell and Organ Senescence Biomarkers
TL;DR: This work focuses on the current methods to assess cellular senescence, discriminating the advantages and disadvantages of severalsenescence biomarkers.
Journal ArticleDOI
Melanocytic nevi and melanoma: unraveling a complex relationship.
William Damsky,M Bosenberg +1 more
TL;DR: This review synthesizes basic scientific insights and data from mouse models with common observations from clinical practice to comprehensively review melanocytic nevus biology, focusing on the mechanisms by which growth arrest is established after BRAFV600E mutation.
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Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells
Valeria Severino,Nicola Alessio,Annarita Farina,Annamaria Sandomenico,Marilena Cipollaro,Gianfranco Peluso,Umberto Galderisi,Angela Chambery +7 more
TL;DR: It is shown here that conditioned media of senescent mesenchymal stem cells (MSCs) contain a set of secreted factors that are able to induce a full senescence response in young cells, and the occurrence of novel-secreted factors regulating MSC cellularsenescence of potential importance for regenerative medicine and cancer therapy is suggested.
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.