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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The retinoblastoma protein - from bench to bedside.
TL;DR: Mouse models with engineered defects in the Rb-phosphorylating kinases provide evidence that moderation of Rb inactivation may be a strategy for the prevention of tumour formation.
Journal ArticleDOI
Runx2 disruption promotes immortalization and confers resistance to oncogene-induced senescence in primary murine fibroblasts.
Anna Kilbey,Karen Blyth,Sandy Wotton,Anne Terry,Alma Jenkins,Margaret Bell,Linda Hanlon,Ewan R. Cameron,James C. Neil +8 more
TL;DR: It is shown that the ability to induce premature senescence in primary murine embryonic fibroblasts (MEF) is a common feature of all three Runx genes, and coupling of stress responses to the cell cycle represents a novel facet of Runx tumor suppressor function.
Journal Article
Inactivation of imprinted genes induced by cellular stress and tumorigenesis.
TL;DR: The data support the concept that silencing of imprinted genes, including methylation of Cdkn1c, constitutes an epigenetic signature of cellular stress and tumorigenesis.
Journal ArticleDOI
Sin3B expression is required for cellular senescence and is up-regulated upon oncogenic stress.
Kathryn B. Grandinetti,Petar Jelinic,Teresa DiMauro,Jessica Pellegrino,Rubén Fernández Rodríguez,Patricia M. Finnerty,Rachel Ruoff,Nabeel Bardeesy,Susan K. Logan,Gregory David +9 more
TL;DR: It is shown that fibroblasts genetically inactivated for the chromatin-associated Sin3B protein are refractory to replicative and oncogene-induced senescence, and modulation of Sin2B-associated activities may represent new therapeutic opportunities for treatment of cancers, indicating that expression of chromatin modifiers is modulated at specific stages of cellular transformation.
Journal ArticleDOI
UNBS5162, a Novel Naphthalimide That Decreases CXCL Chemokine Expression in Experimental Prostate Cancers
Tatjana Mijatovic,Tina Mahieu,Céline Bruyère,Nancy De Nève,Janique Dewelle,Gentiane Simon,Mischaël Dehoux,Ellen van der Aar,Benjamin Haibe-Kains,Gianluca Bontempi,Christine Decaestecker,Eric Van Quaquebeke,Francis Darro,Robert Kiss +13 more
TL;DR: In this paper, UNBS3157 rapidly and irreversibly hydrolyzes to UNBS5162 without generating amonafide and after repeat administration significantly increased survival in orthotopic human prostate cancer models.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
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.