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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Tumor cell senescence response produces aggressive variants.
TL;DR: It is found that subjecting arrested senescent tumor cells to cytotoxic treatments stimulates the clonogenic proliferation of remaining survivors, and the senescence revertants showed a reduced rate of proliferation but increased migration and invasion potential in vitro and increased tumorigenic potential in vivo.
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Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc
Feng-Hou Gao,Xiao-Hui Hu,Wei Li,Hua Liu,Yanjie Zhang,Zhu-Ying Guo,Mang-Hua Xu,Shi-ting Wang,Bin Jiang,Feng Liu,Ying-Zheng Zhao,Yong Fang,Fang-Yuan Chen,Ying-Li Wu +13 more
TL;DR: It was shown that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression, and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest.
Journal ArticleDOI
Wnt Antagonist SFRP1 Functions as a Secreted Mediator of Senescence
TL;DR: It is reported that secreted Frizzled-related protein 1 (SFRP1), a secreted antagonist of Wnt signaling, is oversecreted upon cellular senescence caused by DNA damage or oxidative stress and is necessary for stress-induced senescences caused by these factors and is sufficient for the induction ofsenescence phenotypes.
Journal ArticleDOI
Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer
M E Caldwell,Gina M. DeNicola,C P Martins,Mike A Jacobetz,Anirban Maitra,Ralph H. Hruban,David A. Tuveson +6 more
TL;DR: In this paper, a panel of potential OIS biomarkers in human and murine pancreatic intraepithelial neoplasia (PanIN) was characterized, and only senescence-associated β-galactosidase (SAβgal) activity was specifically enriched in these precursors, compared with pancreatic ductal adenocarcinoma (PDA).
Journal ArticleDOI
Tumour suppressor retinoblastoma protein Rb: a transcriptional regulator.
TL;DR: The molecular mechanisms behind the repressive effects of Rb on E2Fs have come to light in significant details, while those relating to Rb activation of differentiation transcription factors are much less understood.
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.